Technical: Does genetics support ev. or cr.?

[Administrator2]

ZERATUL
Genetic research has provided very compelling evidence that Adam and Eve could not possibly have lived a mere 6,000 years ago. Most of this is from memory, but I can get at the references tomorrow if anyone is interested. Here is the mathematical proof.

6,000 years means that there have been only 300 generations from Adam and Eve to modern humans. That means that there are 300 generations of mutations (in the YEC model) separating us from Adam. The mutation rate per nucleotide has been estimated at 2.5 * 10^-8 per base pair (Source:Mutation Rate Estimate of Human Genome)
Other estimates have also given approximately the same mutation rate.

Let's assume 40,000 genes in the genome. The average gene has around 1500 base pairs. Multiplying the estimated mutation rate by the number of base pairs per gene and then by the number of genes indicates that about 1.5 genes per generation suffers a mutation. Over the course of 300 generations, this means that on average we would have about 450 gene mutations since Adam, or there would be about 0.01 gene versions per gene (on average) in the general population.

Actual data from the Human Genome Project finds that there are around 1,000 times that many gene versions per gene.

What does this imply? The actual mutation rate would have to be 3 orders of magnitude higher than current estimates for the YEC model to work. That rate of mutation is certainly not happening today, and there is no evidence that it has ever been much higher than it is now. Or, the other explanation is that ancestral humans lived 300 generations (times 1000), or 300,000 generations, or 6 million years ago.

The only YEC explanation that I have heard for this appeals to either 1) Directed mutations, or 2) Hypermutations in earlier times. Unfortunately, there is no evidence for either.


DAVID PLAISTED
The article you cited estimated the mutation rate by the assumed common ancestry of humans and apes and an assumed divergence time. For creationists, these are still open to question. I saw a rate of 5 x 10^-7 in an online article (non creationist) which is a lot larger rate. Also if you assume Adam and Eve had 2 different alleles each there could be 4 to start with, and crossing over might give even more.


FROGGIE
If you are looking at mutations in actual genes, your data is going to be biased because only the "good" mutations survive.

I suggest looking at polymorphisms in (what we assume to be) non-coding DNA. For instance--random mutations in introns. I'll look into it and get back to you both.


ZERATUL
David Plaisted:…Also if you assume Adam and Eve had 2 different alleles each there could be 4 to start. with, and crossing over might give even more.

I don't have access to my references tonight, but most geneticists estimate around 1.5-2 new gene mutations per generation. The number you quoted would give some 30 new genes per generation, which is much higher than any estimate I have ever seen. Do you remember the source of this estimate?

But don’t overlook the fact that I have given YEC some highly favorable assumptions. I did not assume that natural selection is taking out the harmful mutations, I did not put in a bottleneck at Noah, and I am counting new alleles in the case of every SNP. If you factor in more reasonable assumptions, especially the fact that most alleles differ at more than one base pair, your hurdle becomes even tougher to overcome.


FROGGIE
This post will describe a study about polymorphisms, or SNP's (stands for single nucleotide polymorphisms).
According to this paper, (Nature 15 February 2001, v409, 928 - 933),
We describe a map of 1.42 million single nucleotide polymorphisms (SNPs) distributed throughout the human genome, providing an average density on available sequence of one SNP every 1.9 kb. These SNPs were primarily discovered through two large projects: The SNP Consortium and the Human Genome Project's analysis of clone overlaps. The map integrates all publicly available SNPs with described genes and other features of the genomic landscape. We estimate that 60,000 SNPs fall within exons, and 85% of exons are within 5kb of the nearest SNP. Nucleotide diversity is found to vary dramatically across the genome, in a manner broadly consistent with a standard population genetic modelas based on population genetic models of human evolutionary history. This high-density SNP map provides a public resource for defining haplotype variation across the genome, and should speed the identification of biomedically important genes as novel targets for diagnostic and therapeutic intervention.

Here is ICR's interpretation of SNP's:
The human genome offers many exciting revelations for the creationist. First, the various human ethnic groups are more similar than scientists originally expected. By comparing the genome sequence with previously known human sequences already publicly available, Celera scientists discovered that humans differ by only one nucleotide for every 1250 in the genome. These differences are called Single Nucleotide Polymorphisms (SNPs). Some creationists will no doubt claim that this confirms the Genesis account of creation and use this statistic as a polemic against racism. What I find surprising by the SNP frequency is that the ethnic groups seem to be too similar. Based on what we know about modern mutation rates and human divergence times, the human genome should contain about twice as much diversity assuming uniform mutation rates in the past. This stands as a fascinating challenge to creation scientists and no doubt holds an interesting clue to the divergence of organisms after the Flood.

Second, as one might expect from the gene frequency, only 1-4% of the SNPs occur in sequences that code for genes.8,9 Thus, the common creationist claim that point mutations almost always result in visibly harmful effects is not technically correct, since 95% of SNP mutations occur in non-coding regions of the genome which have little or no observable effect on the organism. This is certainly not good news for evolution and SNPs are increasingly recognized as a poor method to generate biological diversity. New sources of mutation, such as chromosomal rearrangements (see below), gene transfer, and repeat sequences are being explored as possible sources of mutation for the neo-Darwinian mechanism.

DAVID PLAISTED
[I don't have access to my references tonight, but most geneticists estimate around 1.5-2 new gene mutations per generation. The number you quoted would give some 30 new genes per generation, which is much higher than any estimate I have ever seen. Do you remember the source of this estimate?
But don’t overlook the fact that I have given YEC some highly favorable assumptions. I did not assume that natural selection is taking out the harmful mutations, I did not put in a bottleneck at Noah, and I am counting new alleles in the case of every SNP. If you factor in more reasonable assumptions, especially the fact that most alleles differ at more than one base pair, your hurdle becomes even tougher to overcome.[/I]

Well, I found it on the web, so it has to be right, no? Here is the link: http://www.ultranet.com/~jkimball/BiologyPages/M/Mutations.html

Another thing -- what is an SNP. It took me a long time to understand this. It is a single nucleotide polymorphism that occurs in at least _one percent_ of the population. Low frequency mutations can be much more common than high frequency ones. Also, it only needs to occur this frequently in a subpopulation. To top it all off, it is so expensive to test this frequency criterion that it is almost never done!! So a SNP is in practice just a single site mutation that has been seen at least once or twice.

If you think about the population genetics, the total number of genes will be huge because many mutations will occur at a very low frequency. I don't think the number of SNP's is a problem at all for assuming the human race is 300 generations old.


FROGGIE
Definition from the Human Genome Project website http://www.ornl.gov/hgmis/
Natural sequence variation is a fundamental property of all genomes. Any two haploid human genomes show multiple sites and types of polymorphisms. Some of these have functional implications, whereas many probably do not. The most common polymorphisms in the human genome are single base-pair differences, also called single-nucleotide polymorphisms (SNPs). When two haploid genomes are compared, SNPs occur every kilobase {that's 1:1000} on average...SNPs are abundant, stable, widely distributed across the genome, and lend themselves to automated analysis an a very large
scale...Becuase of these properties, SNPs will be a boon for mapping complex traits such as cancer, diabetes, and mental illness.


Dave:Low frequency mutations can be much more common than high frequency ones.

What? This sentence doesn't make any sense. Low freqeuncy means less common. I must be misunderstanding your point here.


To top it all off, it is so expensive to test this frequency criterion that it is almost never done!!

That is not really true, and also irrelevent.
Another point I would like to make. SNPs are varied between humans because of random copy errors during DNA replication. But it is an error to think of all SNPs as mutations. First of all, because of the redundancy of the genetic code, some base pair changes result in the same protein. Also, most SNPS, like mentioned above, occur in what we think are non-coding regions such as introns. Therefore these changes are not really 'mutations' in the strict definition of the word.


If you think about the population genetics, the total number of genes will be huge because many mutations will occur at a very low frequency.

I'm not sure what you mean here. Are you saying that mutations are causing more genes to form? That is evolution.


I don't think the number of SNP's is a problem at all for assuming the human race is 300 generations old.

Why do you think this?


SCOTT PAGE
To Dave Plaisted
What is your justification for concluding that because there are many SNPs that the "...total number of genes will be huge because many mutations will occur at a very low frequency." That appears to be a non sequitur, at best.


ZERATUL
to: Dave Plaisted
I finally had a chance to read your link. You read the mutation rate incorrectly. The estimated rate was 1/(5 x 10^7), which is actually 2 x 10^-8. This is consistent with, but actually a little lower than the rate from the article I linked to.

Let's cut to the chase, David. If you can solve the following conundrum, I believe you will be the first Creationist to do so. The following is from a recent study released by Genaissance:
"Genetic variation and linkage disequilibrium in 174 human genes"
2,549 SNPs were discovered in approximately 465 kb DNA sequence from 174 human genes with known genomic organization. DNA sequencing was performed on one chimpanzee and 82 unrelated individuals including African-Americans, Asians, European-Americans, and Hispanic Latinos. The data were collected from several gene regions including exons, exon-intron boundaries, untranslated regions and 5' flanking sequences. The average nucleotide diversity for 166 autosomal genes was p=0.063% and q=0.103%, while the average nucleotide diversity for eight X-linked genes was p=0.052% and q=0.070%... "

So, we have a direct count of 2,549 SNPs in 174 genes, or 14.6 SNPs per gene. In the YEC model, these SNPs supposedly came about in 300 generations. What would the mutation rate have to be to see this many SNPs in 174 genes? If a gene has about 1500 base pairs, and the SNPs developed over the course of 300 generations, the mutation rate would have to be 14.6/(1500*300), or 3.2E-5 mutations/base pair generation. This is orders of magnitude higher than ANY estimated mutation rate, including the one you posted above. The implication would be that every generation, an individual would end up with 3.2E-5*1500 base pairs*40,000 genes, or 1920 genes that were new (i.e., neither parent had the exact gene). That means that about 1 out of every 20 genes in the genome be a slightly different version (that neither of your parents have) each generation in the YEC model. This would be an extraordinary rate of evolution.

So, what's going on? How can this be resolved in the YEC model? Evolution explains it nicely, because in the evolutionary model there was a much greater time period over which these SNPs developed.


WEHAPPYFEW
I find it helpful to think about the mutation rate in terms of a single base pair, or a single gene (composed of 1500 pb on average)...

We have a mutation rate of 2 * 10^-8 mutations/pb/generation

We have 300 generations since Adam and Eve.

Simply multiply to find the number of mutations expected per bp or gene.

The answer is 300 * 2 * 10^-8 = 6 * 10^-6 mutations per bp.

Or 9 * 10^-3 per gene


The actual frequency of SNPs observed (by actually counting them) is 2549 out of 465,000. Which equals 1 in 182 = 5.5 * 10^-3 mutations/bp

Similar figures are available from the Human Genome Project. I've seen a SNP frequency of between 1 in 100 to 1 in 300 on their website.

That is almost exactly 1000 times higher than the Creationist prediction. That means the human genome has been accumulating mutations about a thousand times longer than the Creationists postulate... 6,000,000 years instead of 6,000 years. Which precisely matches the prediction made by paleontology of a human-chimp common ancestor at about 6,000,000 years ago.


DAVID PLAISTED
This SNP matter has perplexed me for a long time. I read about 3 places that something only has to occur in one percent of the population to be an SNP. I'd like to know how frequent a typical SNP is -- are most of them just one percent or are most of them about 50 percent or what? Suppose one percent, then a typical individual would have only 1/100 of them or only one SNP every 100,000 base pairs which implies (for 300 generations) one mutation per generation for every 3.33 * 10^-8 base pairs, right? But somehow this doesn't feel right. As for small frequency mutations, with a population of say 5 billion on earth and mutation rate of 2 * 10^-8 there would be just about every mutation occurring somewhere so any SNP would occur in a few people but with very low frequency overall.

Another possibility is that Adam and Eve had haploid genomes with different patterns of SNP and about the same genetic diversity as we see today.

Another possibility is that there was a high rate of mutation in the past -- some creationists think that radiation caused the flood and if so it could also have caused a lot of mutations in a short time.

As for why there are so many genes, again the question is how frequent they are. But it could be that plagues swept through the population frequently and individuals with certain mutations were more likely to survive. So if these mutations had some selective advantage they could spread much faster.

There is another interesting fact -- I don't have my references but SNP's tend to be correlated with each other in 50 kb stretches. This puzzles biologists and they hypothesize that recombinations are restricted to certain parts of the genome. It is also possible that this simply shows that the human population is very young. I think there are about one recombination every 10^8 base pairs per generation -- for 300 generations there would be one every 3 * 10^5 roughly -- this could explain why SNP near each other are correlated. If you assume Adam and Eve had certain patterns of SNP or that they arose by rapid mutation on the few individuals on the ark then recombination would break the genome into small segments that originated from one individual.


FROGGIE
I think you are confusing amount of SNPs per genome, and the actual SNP itself. The SNP percents only make sense if you are talking about the human genome as a collective. So, when we compare your DNA sequence to mine to someone elses, etc. . . we will find, on average, single point differences somewhere between 1:100 to 1:1000 base pairs.

So geneticists are currently trying to map the SNP locations. For example, lets say an SNP occurs at the fifth base downstream from the start site in the hemoglobin gene (I'm making this up for an analogy). Every human has a fifth base pair in their hemoglobin gene. Therefore every human has that SNP loci. But the difference is, Joe may have an "A" there, while I have a "G." Does this make sense? And the more differences we find, the more genetically different we are.


Suppose one percent, then a typical individual would have only 1/100 of them or only one SNP every 100,000 base pairs which implies (for 300 generations) one mutation per generation for every 3.33 * 10^-8 base pairs, right? But somehow this doesn't feel right.

That's because you can't talk about one person having SNPs. There is nothing to vary if you talk about only one person. Mutations/SNPS are only relevant when you are making comparisions.


As for small frequency mutations, with a population of say 5 billion on earth and mutation rate of 2 * 10^-8 there would be just about every mutation occurring somewhere so any SNP would occur in a few people but with very low frequency overall.

Not sure what you mean here. Could you please explain to me what "small frequency mutations" are? I'm not trying to be mean by asking this again, I honestly dont' know what you mean.

Keep in mind that most mutations within a gene are harmful, will die in utero, and will not contribute to our analyses.


Another possibility is that Adam and Eve had haploid genomes with different patterns of SNP and about the same genetic diversity as we see today.

Can you think of a way to test this hypothesis? To my knowledge, we have no evidence that humans ever existed as hapliod forms, like many plants and invertebrates do.


Another possibility is that there was a high rate of mutation in the past -- some creationists think that radiation caused the flood and if so it could also have caused a lot of mutations in a short time.

Would this radiation/mutagen have acted similarly on other organisms? If this is true, than we should find evidence for it in other species as well. Can you think of ways to test this hypothesis?


As for why there are so many genes, again the question is how frequent they are. But it could be that plagues swept through the population frequently and individuals with certain mutations were more likely to survive. So if these mutations had some selective advantage they could spread much faster.

Do you mean to say SNPs instead of genes? I'm not sure what you are asking here. The original question I posed at the beginning of this forum was referring to the fact that we don't have as many genes as we thought we did.


There is another interesting fact -- I don't have my references but SNP's tend to be correlated with each other in 50 kb stretches. This puzzles biologists and they hypothesize that recombinations are restricted to certain parts of the genome.

Recombination is when chromosomes swap arms during meiosis. If you find a reference, please link!


It is also possible that this simply shows that the human population is very young. I think there are about one recombination every 10^8 base pairs per generation -- for 300 generations there would be one every 3 * 10^5 roughly -- this could explain why SNP near each other are correlated.

How so? I am not following your argument here. Please explain further.


If you assume Adam and Eve had certain patterns of SNP or that they arose by rapid mutation on the few individuals on the ark then recombination would break the genome into small segments that originated from one individual.

Recombination does not break the genome into small segments. In fact it mixes up the genes from each parent.

[ January 21, 2002: Message edited by: Administrator ]

 

[Administrator2]

HELEN
Short points here:

1. see Gene. 2000. 261:27-33 - no proposed mechanisms "can simultaneously account for the disparate patterns..." etc etc

2. as long as the horse variations can still interbreed, the assumption is good that they are from an initial kind and even an initial pair off the ark. If the chromosome differences don't bother them, then maybe the genetics argument for common descent isn't all it's cracked up to be.


FROGGIE
Here's some stuff from talkorigins, under "29 evidences for macroevolution":

Prediction 29: Genetic rates of change.
Rates of genetic change, as measured by nucleotide substitutions, must also be consistent with the rate required from the time allowed in the fossil record and the sequence differences observed between species.

Confirmation:
What we must compare are the data from three independent sources: (1) fossil record estimates of the time of divergence of species, (2) nucleotide differences between species, and (3) the observed rates of mutation in modern species. The overall conclusion is that these three are entirely consistent with one another.
For example, consider the human/chimp divergence, one of the most well-studied evolutionary relationships. Chimpanzees and humans are thought to have diverged, or shared a common ancestor, about 6 Mya, based on the fossil record (Stewart and Disotell 1998). The genomes of chimpanzees and humans are very similar; their DNA sequences overall are 98% identical (King and Wilson 1975; Sverdlov 2000). The greatest differences between these genomes are found in pseudogenes, non-translated sequences, and fourfold degenerate third-base codon positions. All of these are most likely very free from selection constraints, since changes in them have no functional or phenotypic effect. Since these regions are nonfunctional, all mutational changes are incorporated and retained in their sequences. Thus, they should represent the background rate of spontaneous mutation in the genome. These regions with the highest sequence dissimilarity are what should be compared between species.

Given a divergence date of 6 Mya, the maximum inferred rate of nucleotide substitution in the most divergent regions of DNA in humans and chimps is ~1.3 x 10-9 base substitutions per site per year. Given a generation time of 15-20 years, this is equivalent to a substitution rate of ~2 x 10-8 per site per generation (Crowe 1993; Futuyma 1998, p. 273).

Background spontaneous mutation rates are extremely important for cancer research, and they have been studied extensively in humans. A review of the spontaneous mutation rate observed in several genes in humans has found an average background mutation rate of 1-5 x 10-8 base substitutions per site per generation. This rate is a very minimum, because its value does not include insertions, deletions, or other base substitution mutations that render these genes completely nonfunctional (Mohrenweiser 1994, pp. 128-129). Thus, the fit amongst these three independent sources of data is extremely impressive.

Similar results have been found for many other species (Li 1997, pp. 180-181, 191). In short, the observed genetic rates of mutation closely match inferred rates based on divergence times and genome differences, and, therefore, they can easily account for the genetic differences observed between the genomes of species.

Potential Falsification:
It is entirely plausible that measured genetic mutation rates from observations of modern organisms could be orders of magnitude less than that required by rates inferred from the fossil record and sequence divergence.


HELEN

Ashby Camp showed Theobald’s reason on that point to be false: http://www.trueorigin.org/theobald1f.asp#pred29

There is a difference between what evolution accommodates and what it predicts.


DAVID PLAISTED
Recombination does not break the genome into small segments. In fact it mixes up the genes from each parent.

I'm still unclear about what is the frequency of SNP. Suppose we have these people with these sequences of nucleotides (I'll use ABCD instead of ACGT in order to avoid the implication of specific bases)

Tom ABACBA
Sue ABADBA
Jill BBACBA
Joe ABDCBA

Now Tom and Sue differ in one site, Sue and Jill in two etc. But in the entire population of four people, there are three places where at least two people differ. So does this population have 3 SNP's? If so how does this correlate with the fact that Tom and Sue only differ in one site and that other pairs differ in a max of two sites? It is claimed that 2 individuals differ in about 1/1000 of their bp but also that about 1/1000 of the bp are SNP for the entire population. These statements appear to be logically inconsistent.

My terminology was to say someone "has" an SNP if their base pair at the site is in the minority (or at least not the majority) so Tom has no SNP and Sue, Jill, and Joe have one each, in my manner of speaking. I think it is in this sense that the one percent requirement is made. So in this sense, what is the frequency of the typical SNP?

As for Adam and Eve, consider a particular chromosome, say chromosome 1. Adam has 2 copies and so does Eve, for 4 in all. It is possible that considering any pair of these they might differ in 1/1000 of the base pairs so the genetic diversity we see might have been present from the beginning. (This is just a hypothesis given for the sake of logical completeness.)

When I say small frequency mutations I mean those that occur in only a tiny fraction of the population. If only 1/1000000 of the population has a given base at a given site then it is a small frequency mutation -- but enough to guarantee that a few copies of some rare allele exist in the population.

It's a good question to see if there is some way to test if the mutation rate were higher in the past due to radiation or some other environmental factor. I don't have any ideas how to test this though.

As for the number of alleles, if certain mutations have a selective advantage they will tend to spread in the population and this can have the effect of increasing the number of alleles more than one would expect on the basis of the hypothesis that all mutations are neutral. This could explain why there are 22 alleles (or whatever) that occur fairly frequently in the population.

Molecular clocks are notorious for running at different rates. This does not seem to confirm the theory of evolution at all.

Here is the recombination part -- I probably should have said "crossing over"?

Suppose Mary and Bill have Sue as a daughter. Suppose Mary has two copies of chromosome 1. We'll call them A and B. One came from her mother (Sue's grandmother) and one from her father (Sue's grandfather). (I'm sorry to speak at such a low level but my meaning seems to get lost otherwise.) Now, Bill also has 2 copies of chromosome 1, which we call C and D. Now Mary's egg, that gave rise to Sue, has a chromosome 1 that is a blend of parts of A and B (if I understand correctly). This is what I referred to as breaking the chromosome in pieces -- of course they are still joined together. Also, Bill's sperm that gave rise to Sue has a chromosome 1 that is a blend of parts of C and D. So some parts came from each. Thus Sue will have two copies of Chromosome 1, one a blend of A and B and one a blend of C and D. If Sue has a child, these two will be combined, and Sue will pass on a chromosome 1 that has parts from A, B, C, and D, possibly with some mutations. Anyway, this process continues with each generation, and contiguous segments of base pairs have the same pattern of inheritance until they get split apart in this way by a crossing over (which I was calling a recombination?) So if you still have large correlations between nearby base pairs it can be an indication that the population is young -- Sue's child will have large segments of chromosome 1 from Sue that appear nearly identically in Mary or Bill. Thus the high correlation in SNP's within 50 kb may indicate that the human population is very young.

Now it's time to read from Dick and Jane ...


THE BARBARIAN
Camp is discussing the evidence that supports evolutionary theory. These aren't, strictly speaking, predictions.
Rather, they are the facts that are explained by evolutionary theory.

Predictions of evolutionary science are both more diverse and more detailed. For example, evolutionary theory predicted that Lord Kelvin was wrong in his insistance that the Earth was only a few millions of years old. Darwin pointed out that his theory required more time than Kelvin's theory allowed. Later, when radioactivity was discovered, Kelvin grudgingly admitted that he had been wrong.

On the other hand, Huxley, based on anatomy and evolutionary theory, predicted birds must have been evolved from dinosaurs. Later, we find unequivocal dinosaurs with feathers.

Based on evolutionary theory, scientists point out that whales must have had functional legs at some point. I can remember when a prominent creationist declared a whale with legs would make him into an evolutionist.

Now we find several examples of whales with legs, including at least one that could actually walk on them. And now, molecular biology reveals that whales are most closely related to ungulates, as predicted by the evolutionary theory.

Scientists, based on evolutionary theory, predicted that intermediates between apes and humans must have existed. Later, we find Australopithecines and ancient species of Homo that confirm this prediction.

Based on the fossil record, and on evolutionary theory, scientists predicted that at some point, there must have been fish with functional legs. And now we have found some, fulfilling the prediction.

And so on, in endless detail. Of course, all these fulfilled predictions do then become further evidence for evolutionary theory.


HELEN
Barbarian, you have made a lot of statements and given not one reference. Would you please detail the predictions you speak of? Who made them? When? Where? In what context?

In the meantime, you said that Camp was discussing “the facts that are explained by evolutionary theory.”
First of all, Camp was discussing Theobald’s use of the material. Secondly the facts involved are facts that evolution SEEKS to explain, and not always successfully.

The word ‘accommodate’ is not the 'current jargon,' it is a correction based on real English definitions regarding what is going on with evolution and 'evidence' and 'predictions.'

Here's a prediction before I even read the rest of the post: evolution predicts nothing but accommodates everything, by new impossibilities when necessary.
I can remember when you said reefs couldn't grow very fast and that was one reason evolution had to be true!


Now we find several examples of whales with legs, including at least one that could actually walk on them.

No. Now a few fossils have been found that are entirely dissimilar to whales but which evolutionists have trumpeted as 'transitionals'! There's a world of difference between what you are so confidently stating and the truth.


And now, molecular biology reveals that whales are most closely related to ungulates, as predicted by the evolutionary theory.

Molecular biology reveals nothing of the sort. It shows similarities in some sequences and you are interpreting it the way you want.


Scientists, based on evolutionary theory, predicted that intermediates between apes and humans must have existed. Later, we find Australopithecines and ancient species of Homo that confirm this prediction.

Gee disagrees with you. And the anthropologists continue their arguments. Your confident statements have little or nothing to do with reality, Pat.


Based on the fossil record, and on evolutionary theory, scientists predicted that at some point, there must have been fish with functional legs. And now we have found some, fulfilling the prediction.

No, you have found fossils of species which you declare to be what evolution has been searching for. What they really were is not something you or I or anyone knows. Interpretations simply are not facts….

And so on, in endless detail.
Yes, I know. "Overwhelming Evidence" -- based on interpretations, accomodations, or outright frauds.

Of course, all these fulfilled predictions do then become further evidence for evolutionary theory.
"Interpreting" is so much fun!


I'm not sure if Camp has also confused the evidence for evolution with predictions of evolutionary theory. But no matter how he tries to spin it, it's there.

Which shows me you have not read the article.
It is evolutionists who are so famous for just-so stories -- how the fish got his legs.... how the dinosaur got his wings.... how the one-celled organism got its arms...


THE BARBARIAN
"Explain" is the scientific term. "Accomodate" is the euphemism currently in use by the creationists. Just so we know to what the words are referring.

Lord Kelvin was wrong in his insistance that the Earth was only a few millions of years old.
Here's a synopsis of the story: http://www.uh.edu/engines/epi1568.htm

and:
http://www.time-travel.com/earth.htm
http://www.nobel.se/physics/articles/fusion/sun_1.html


I can remember when you said reefs couldn't grow very fast and that was one reason evolution had to be true!

No. It's true that reef-building coral grows about 0.5cm per year in ideal conditions. And it is true that we know the coral atolls are very ancient because of that fact. But it merely puts a limit on how young the earth can be. Has nothing to do with evolution as such.

There are anatomically intemediates between earlier ungulates and later whales. There are more of them being found regularly now, and they are filling in the gaps nicely. For a good discussion of these finds, you can check out: http://www.neoucom.edu/Depts/ANAT/Locomotion.htm

Be sure to click on the links at the bottom of the page, a lot of detail on the way cetacean characteristics evolved is available. Things like the evidence for being able to use salt water to drink, for example, and how Ambulocetus explains why whale flukes are horizonal instead of vertical.


… whales are most closely related to ungulates, as predicted by the evolutionary theory.

---Molecular biology reveals nothing of the sort. It shows similarities in some sequences and you are interpreting it the way you want.

One would have to be pretty resistant to reality to deny that related animals have similar DNA. It is the same process by which we establish paternity and descent in humans. So we know it works.

go to the link http://www.personal.u-net.com/~paleomod/p97/aca1.htm
Classify this one as a fish or an amphibian, and tell me the criteria you used. If you can't distinguish the two orders, then it's pretty pointless to say that they aren't related.


Interpretations simply are not facts...

Facts are facts. I've given you quite a number of them here. I'd especially be interested in how you classify Acanthostega. Good luck.


Which shows me you have not read the article.

I've read it. I just don't see any sign that he imagines evidence is the same thing as predictions. Could you point me to that part?


FROGGIE
Helen,
Although I could not find the exact trueorigins site, I did find 90 creationist sites linked to from talkorigins. http://talkorigins.org/origins/other-links.html#creationism
Lest you think this is evidence that their version of creationism is true--let me warn you that these web sites/beliefs differ way more from each other than do YEC versus evolution! Talkorigins has this to say about the creationist movement:
The differences between types of creationism are not minor. Most of the creationist beliefs described below are mutually exclusive, and often their differences are as great as their differences with evolution. Many creationists disagree as much with other creationists as they do with evolutionists.

Oh, BTW, guess how many evolution sites are linked to by true origins. By my assessment, none. So who's more biased about looking at the evidence? Hmmm. . . I wonder.

Anyway back to science.

Trueorigins accuses Douglas Theobald of picking and choosing evidence here:
If the amino acid sequence in such a protein was not the same or “similar” in two or more species, evolutionists simply would vary the time of divergence and/or the mutation rate, which is claimed to vary for different proteins, to account for the differences.

But doesn't Ashby Camp do the same thing? He (she?) attributes similarities that we find to a common creator (instead of common descent). But when a difference is found, than that protein must have unknown functions that the creator knows but we don't.

But even if there were no unknown design constraints on the gene for cytochrome c, how could one be sure that God would not conserve amino acid sequences (or the underlying codons) when creating cytochrome c in separate species? After creating cytochrome c in the first organism, it certainly is conceivable that he would make changes to that blueprint only when necessary for his purpose. In other words, the default in this instance may be similarity rather than dissimilarity. There is no basis for demanding that God introduce novelty for novelty’s sake.

Camp also points out that

As J. Craig Venter of Celera Genomics explained in the press conference announcing the sequencing of the human genome:"Our understanding of the human genome has changed in the most fundamental ways. The small number of genes—some 30,000—supports the notion that we are not hard wired. We now know the notion that one gene leads to one protein, and perhaps one disease, is false."
One gene leads to many different protein products that can change dramatically once they are produced. We know that some of the regions that are not genes may be some of the keys to the complexity that we see in ourselves. We now know that the environment acting on our biological steps may be as important in making us what we are as our genetic code. (Bethell, 52.)

A common creationist claim is that a few mutations in a few genes is not enough to produce large-scale changes.
Now through the genomic studies, we can prove that it is. Yes, one gene can code for many proteins. Alter that one gene, and you have potentially altered an entire pathway or development. Proof against evolution? I don't see it that way.

Venter's quote above also debunks a common probability argument against evolution, which uses the one-gene-->one protein hypothesis to show how "unlikely" evolution is. Yes it is unlikely using that very strict narrow definition of genes. But our genes do not behave that way, as Ashby pointed out.

If the gene for cytochrome c, for example, does more than code for that particular protein, then its other functions may influence the order of its codons and thus influence the order of amino acids in cytochrome c. Without knowing all that a gene does within an organism and how it accomplishes those functions, one cannot know the gene’s design constraints and therefore cannot know the corresponding constraints on amino acid sequences.

This is true. I fail to see how creationism overcomes this problem too, unless of course they understand the motivations behind God better than scientists understand molecular biology. Perhaps they do, who knows?

For example, humans and rhesus monkeys supposedly diverged from a common ancestor as long as 50 million years ago,[37] but the only difference in their cytochrome c is at position 66, which is isoleucine in humans and threonine in rhesus monkeys. This strong conservation may mean that the gene for cytochrome c is subject to needlessly efficient error correction, but it also may mean that the gene is performing unknown functions that are responsible for or contribute to its conservation.

Or it could mean that the conversion of isoleucine to threonine is an inocuous mutation. I don't have my biochem book here, but aren't they both non-polar amino acids? I can think of an easy way to test this hypothesis. Make the two recombinant forms in a lab, and test the functions in a functional assay (I actually do what's called a cytochrome C assay in my lab--i'm sure it could be modified for this purpose). Compare their functions. If the two variants have the same redox activity, we can conclude that the mutation is not harmful. Of course we could not be sure that cytC is not doing something else. But I fail to see how that would disprove evolution.

 

[Administrator2]

WEHAPPYFEW
OK, folks, we are straying far from the intended debate format and topic here...
David, perhaps we can clear up your confusion about SNPs. I am somewhat surprised that you could not get a grasp of the idea from the numerous websites related to the Human Genome Project.

They mapped the human genome. They constructed a "standard" genome - composed of the base pairs found in the majority of the test subjects. SNPs are defined as the differences from that standard. On average, any human will differ from the "standard" sequence at about 1 in a few hundred base pairs. (http://www.ornl.gov/hgmis/faq/snps.html)
Any 2 people differ by 1 in 1000, according to froggie's sources, while differing from the "standard" by 1 in a few hundred. So can we infer that any 2 people will share about 2/3rds of their SNPs?

Maybe, but I'm not sure we are comparing apples to apples here. It is possible that the 2 figures are referring to different things. 1 in 1000 might refer to a comparison against one of the databases of mapped SNPs - which are a small subset of the total SNPs extant in the whole population.

The Genassaince study found 1 difference in 182 bp. Most of these differences are from fairly common SNPs - found in maybe a few percent of the population. Go check the ALFRED database to see SNP frequencies for the few genes that have been thoroughly checked for them. http://alfred.med.yale.edu/alfred/index.asp

To use David's example:

Tom ABACBA
Sue ABADBA
Jill BBACBA
Joe ABDCBA

The "standard" genome for this sequence would be ABACBA. 3 of the 4 individuals have a SNP. Thus the frequency of SNPs in this case is 1 in 8.


Your point about low frequency mutations is correct, even if it is stated in a way that confuses the flour out of the other participants. Given the current high population of humans, and the estimates of mutation rates, every possible point mutation can be expected to occur several times in the population. This does not solve the problem, however, SNPs are still too frequent by 1000 times.


"Molecular clocks are notoriously variable"

This argument is misapplied in this case. The clocks with the high variability are in the mitochondrial DNA or in protein coding regions subject to hypermutation and/or intense selection pressure, IIRC. The frequency of SNPs is a kind of "clock" that resides in the ENTIRE genome - coding and non-coding. It is, in effect, a measure of the average mutation rate across the whole genome. Even if tiny parts are subject to selection, hypermutation, or whatever, the AVERAGE rate is the important figure. Once you get a grip on what SNPs are, how they occur, etc, there is no way to argue around the three orders of magnitude shortfall in the Creationist scenario.


FROGGIE
Thanks for the links, whf, and the explanation of SNPs.

Here's an abstract from a Nature paper, 2001 Feb 15;409(6822):928-33 :
A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms.
We describe a map of 1.42 million single nucleotide polymorphisms (SNPs) distributed throughout the human genome, providing an average density on available sequence of one SNP every 1.9 kilobases. These SNPs were primarily discovered by two projects: The SNP Consortium and the analysis of clone overlaps by the International Human Genome Sequencing Consortium. The map integrates all publicly available SNPs with described genes and other genomic features. We estimate that 60,000 SNPs fall within exon (coding and untranslated regions), and 85% of exons are within 5 kb of the nearest SNP. Nucleotide diversity varies greatly across the genome, in a manner broadly consistent with a standard population genetic model of human history. This high-density SNP map provides a public resource for defining haplotype variation across the genome, and should help to identify biomedically important genes for diagnosis and therapy.


Here's another article.
Science 1996 Mar 8;271(5254):1380-7
Global patterns of linkage disequilibrium at the CD4 locus and modern human origins. Tishkoff SA et al.

Haplotypes consisting of alleles at a short tandem repeat polymorphism (STRP) and an Alu deletion polymorphism at the CD4 locus on chromosome 12 were analyzed in more than 1600 individuals sampled from 42 geographically dispersed populations (13 African, 2 Middle Eastern, 7 European, 9 Asian, 3 Pacific, and 8 Amerindian). Sub-Saharan African populations had more haplotypes and exhibited more variability in frequencies of haplotypes than the Northeast African or non-African populations. The Alu deletion was nearly always associated with a single STRP allele in non-African and Northeast African populations but was associated with a wide range of STRP alleles in the sub-Saharan African populations. This global pattern of haplotype variation and linkage disequilibrium suggests a common and recent African origin for all non-African human populations.


QXR37
Scientists, based on evolutionary theory, predicted that intermediates between apes and humans must have existed. Later, we find Australopithecines and ancient species of Homo that confirm this prediction.

Helen:
Gee disagrees with you.

I believe you have misunderstood Gee's arguments. Although he does argue that we can never know if a specific fossil is an "ancestor" or merely a "cousin," he does not dispute that fossils showing mixtures of traits from different groups, like the australopithecines, provide strong evidence that there is an evolutionary relationship between these groups. In his book you can find plenty of sections where he talks about fossils with mixes of traits that provide this sort of evidence, like the early fish-like tetrapods and the recent feathered dinosaur finds.


FROGGIE
One more link for people out there who either 1) have free time or 2) are ignoring writing their thesis to participate!
Science article with lots of data. http://www.sciencemag.org/cgi/content/full/286/5439/458?ijkey=wdICO7J7uPLqc


SHAUNR
Hey here is a genetics question for creationists. Studies have shown that chimpanzees and humans share 98.4 percent of their DNA. They even have the same defective gene that prevents them from making their own vitamin c, like most mammals.Humans and chimps are as closely related genetically as horses and zebras. Now, evolution can explain why this is so. What’s the creationist explanation?


JOHN PAUL
Whats the creationist explanation?

Common Creator + common morphologies = DNA similarities.
You can't get there from here http://www.creationequation.com/DrJWells_YouCantGetThereFromHere.htm
"Features of the fertilized egg that seem to be more fundamental than the genes in controlling development include patterns imprinted on the membrane by the mother, and cytoskeletal patterns generated by centrosomes. In order for evolution to occur, these features (and whatever other features may turn out to be involved) would have to change in concert with the genes.
A neo-Darwinian explanation based on simple changes in DNA sequences is fundamentally incapable of accounting for evolutionarily significant changes in development. Within a neo-Darwinian framework, the organism can't get there from here."


DAVID PLAISTED
My last reply was edited by the moderator -- perhaps he did not notice that I had inserted replies into the quote.
Here again, different format:
You say I am confused about SNP. This may be so but I think you are, too.

You say that on average, any human will differ from the standard DNA sequence every few hundred base pairs. I think you are confused here and it should be: Every human differs from the standard roughly one in every 2000 base pairs.

In my example one could say that there are 3 SNP in 6 base pairs so the frequency of SNP is 3/6. One could also say 3 SNP in 24 base pairs total for a frequency of 1/8.

Here are some quotes about the correlations from Science vol 293 27 July 2001 pp. 583-5:
"Haplotypes are simply long stretches of DNA--including perhaps as many as 100,000 bases -- at a given location on a chromosome. To their surprise, genome researchers have found that many such blocks come in just a few different versions ..."

"Computer simulations suggest that haplotype blocks -- DNA stretches containing the same SNP pattern -- would stretch only 3000 to 8000 bases ... "

"... haplotype blocks are at least 10 times longer than predicted, and there are a relatively small number at each chromosomal position. For some sequences of 50,000 bases, for example, just four or five patterns of SNPs -- that is, four or five different haplotypes -- might account for 80% to 90% of the population."

To me this is potentially evidence that the human race is young as suggested in an earlier post. The Science article suggests irregularities in recombination, or a population bottleneck, as possible causes.


To Barbarian: It's also not surprising that there are genetic similarities between all members of this hypothesized transitional [whale] sequence -- after all, they were selected as candidates for such a transition based on morphological similarities, so one would only expect them to be genetically similar as well.


FROGGIE
Well, John Paul took us on a different course, which is fine with me because I understand genetic control of development much better than SNPS! I will be discussing the link JP gave us here, written by Dr. Wells: You can't get there from here. My source is my textbook, “Molecular and Cellular Biology” written by Harvey Lodish et al, in1995. So it’s a little out of date, but the basic mechanisms I will be discussing still hold true.

(From Wells)beneficial mutations in developmental programs have not been observed.

I don’t think this is completely true. Of course by and large it is true—but keep in mind that evolutionists accept a very old earth, which gives evolutionary mechanisms much more time than our lifetimes to get the diversity of organisms.


(from Wells) To be sure, genes (DNA sequences) affect development, but many lines of research suggest that body plans and other morphological features are laid down prior to and largely independently of gene expression.

What Wells is referring to is embryo patterning, and while he is correct in stating that some of the body plan is laid down before development , he is not correct when he says it is independent of gene expression. The original patterning of an embryo is laid out by maternal mRNA. What is mRNA? It’s gene expression (but of the mother).


(from Wells) Genetic mutations affect development primarily by (a) damaging molecules needed for normal development, and (b) damaging binary switches that direct development along pre-determined lines that are not controlled by the genes themselves.

I don’t think so. Gene expression is much more complex than any of us can truly comprehend (at least for now!).
Here’s what Lodish has to say on the subject:
(From Lodish) These studies (referring to the summation of gene control in development studies of drosophila, mice, yeast, etc) have revealed that many developmentally important genes encode transcription factors, suggesting that regulation of transcription is a primary strategy for controlling development in all organisms. In this chapter we consider the regulation of gene expression during development in several model systems. These studies highlight the diverse molecular mechanisms used to control gene expression as well as the conservation of basic strategies to generate different developmental states.

Wells oversimplifies the definition of gene expression, and he is somewhat successful in showing that this very simple model of gene expression is not enough to explain how evolution occurs. But scientists already knew that—this is why they are still studying it.


(from Wells) The first effect (referring to his point (a) above) is analogous to damaging building materials during the construction of a house; if 2x4s that should be eight feet long are actually shorter or of varied lengths, the shape of the house will be affected.

Interesting analogy. Too bad Wells isn’t familiar with Dr. Schmidt’s research down the hall from me. Stuff taken from his web site at MSU:
(from Dr. Ed Schmidt) Many "situation-specific" transcription factors arose during metazoan evolution to regulate novel processes that arose at each step. However, these factors can only transmit signals if RNA polymerase can respond to them. We hypothesize that, to achieve this communication, the transcription machinery co-evolved with the novel factors and their target genes. Using sequence-based phylogenetic analyses, we look for "embellishments" on the basal transcription machinery that might represent signaling "switch-boards" for gene regulation. Once such sequences are found, we create mice lacking these embellishments, and we ask what physiological processes are disrupted as a consequence.

He studies this particular protein called TBP, or Tata Binding Protein (a transcription factor). Somewhere along vertebrate evolution, a new N-terminus arose that is longer, and different than the non-vertebrates. However, the C-terminal domain (the part that binds to the DNA) is highly conserved—even when you look at yeast. His lab speculates that this addition to the protein allowed vertebrates to help develop a vertebrate-specific function such as the immune system. So in this case, adding 8-feet long boards allowed the organism to build a different type of “house.”


(From Wells) The second effect is analogous to damaging switches in a railroad switchyard; if cars carrying heating oil destined for Iowa are sent down a siding meant for an Amtrak Metroliner, they will end up in the wrong place.

This is a bad analogy but I’ll turn it into a more appropriate one. If Amtrak is a living & adaptable system, this new switch will provide the incentive for Amtrak to find a new and different use for the oil. Hence it will evolve.


(From Wells) Features of the fertilized egg that seem to be more fundamental than the genes in controlling development include patterns imprinted on the membrane by the mother, and cytoskeletal patterns generated by centrosomes. In order for evolution to occur, these features (and whatever other features may turn out to be involved) would have to change in concert with the genes.

This is true. No scientist would dispute that. Of course there are many changes you could hypothetically make in the DNA sequence which would simultaneously affect the cytoskeletal patterns and the signaling mechanisms these patterns affect.


A neo-Darwinian explanation based on simple changes in DNA sequences is fundamentally incapable of accounting for evolutionarily significant changes in development. Within a neo-Darwinian framework, the organism can't get there from here.

Yes, when you put it that way. Replace the word “simple” in the quote above with Lodish’s “the diverse molecular mechanisms used to control gene expression”, and now you can then change incapable to capable, and can’t to can.

Developmental biology studies have provided much evidence for evolution, which is good because the theory of evolution as proposed by Darwin didn’t even know what a gene was. So the predictions that evolutionary theory would make are now coming true as we study genetics. One great example is the homeobox genes of Drosophila.

(From Lodish) A milestone in developmental biology was the discovery that a region of homology existed in all the structural genes within the major drosophila homeotic complexes…This homologous region encodes a bout 60 contiguous amino acids in each of the proteins encoded by the HOM-C genes…Shortly after this discovery, mammalian homologs of the HOM-C genes were isolated…Recent studies have shown that these mammalian genes, like the homologous drosophila genes, play a critical role in regulating the development of specific regions along the anterior/posterior axis…the genomic order of the BX-C and ANT-C genes is colinear with the order of expression of these genes along the ant/post axis of Drosophila. This same feature of genomic organization has been demonstrated for the mouse Hox genes. Conservation of this pattern of gene expression suggests that a common mechanism regulates development of specific regions along the anterior/posterior axis in both Drosophila and mammals.

A picture speaks a thousand words. I wish you could all see figure 13-45, which compares the drosophila genes with the mammalian homologs (which have been duplicated a couple times so mammals have 4 copies where the fly has 1). It is very convincing evidence of evolution!


ZERATUL
I have been wondering about a falsification of the Creationist arguments on morphology, DNA, and an Intelligent Designer. Let's see if I have this correct. Common morphology = similar DNA = common Designer. Is that about right?

If so, would the following serve as falsification of this theory? Let's assume that the DNA of the following generic species is sequenced: Wolf, hippo, lion, rat, bat, whale, eagle, shark, fruit fly, and a sea snake. If I compare the shark to the various mammal species, I should expect to see the closest correlation to the whale. Correct? If I compare the eagle or the fruit fly to the mammals, I should see the strongest correlation to the bats. Admittedly the overall correlation between fruit flies and mammals will be low, but when I am comparing flies to other animals I should see a stronger correlation when I am looking at animals that fly. Failure to find the expected correlations would serve as evidence against the theory.
Agreed, or not? If you disagree, could you explain your reasons?

If I compare the sea snake to all the other animals, what should I expect to find and why? I can give a pretty good idea of many of the relationships that the ToE would predict without even knowing any of the sequences. Can you give me a good reason, using Creation Science, as to why the bird might be more closely related to the snake than the bat?


FROGGIE
In response to the claim that Dr. Wells made above, "beneficial mutations in developmental programs have not been observed," Here's an interesting tidbit I just read in the article entitled, "Coding sequence evolution," by Kreitman and Comeron, Current Opinion in Genetics and Development, 1999, vol 9, page 637-641.
They were talking about some interesting work done by Dean and colleagues. They are researching biochemical pathways, which are similar to developmental pathways (highly regulated, depend on environment and genetics, etc). Here's a snip of the article:

Dean and colleagues investigated an ancient evolutionary change in isocitrate dehydrogenase that shifted the enzyme from being NAD-depended to being-NADP-dependent. This evolutionary event, it is argued, allowed an ancestor of modern eubacteria to utilize acetate as a carbon source, thus opening up an immense new ecoogial niche for bacterial exploration. By [using X-ray crystallography and mutation analysis], they identified six amino acids that together could cause a shift in preference of IDH from NADP to NAD. Two additional changes allowed the modified E coli enzyme to function at comparable levels to the eukaryotic NAD-dependent enzyme...in this manner these authors were able to infer the sequence of the ancestral IDH and to elicidate likely changes that occured over three billion years ago to bring about this major adaptation!

Here's an abstract of some of the work. I found this quote quite interesting: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9096353&dopt=Abstract
Hence the adaptive history of molecular evolution is amenable to experimental investigation.
(amenable of course means agreeable.)

Another abstract has this to say: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8901552&dopt=Abstract

Guided by x-ray crystal structures and molecular modeling, site-directed mutagenesis has been used to systematically invert the coenzyme specificity of Thermus thermophilus isopropylmalate dehydrogenase from a 100-fold preference for NAD to a 1000-fold preference for NADP. The engineered mutant, which is twice as active as wild type, contains four amino acid substitutions and an alpha-helix and loop that replaces the original beta-turn. These results demonstrate that rational engineering of secondary structures to produce enzymes with novel properties is feasible.

All mutations are harmful and do not produce any new or novel mechanisms? I don't think so!


ZERATUL
Since it has gotten buried back on page 1, and since nobody addressed it, I wanted to reiterate the argument that was originally made. By performing a direct count of SNPs, we find that the required mutation rate would be over 3 orders of magnitude higher than current observations in the YEC model. As I pointed out, new genes would have to appear at a rate of almost 2,000 per generation if we all descended from Adam 6,000 years ago.
Wehappyfew’s calculations show the expected SNP frequency based on the YEC model, and contrasts that with the frequency based on an actual count. So far (unless I missed it), this remains unchallenged. Oh, there was a bit of misdirection, but nobody has seriously tried to refute this.

What gives? Is the human population actually 6 million years old instead of 6,000? Evidence from population genetics tends to indicate that it is.

[ January 21, 2002: Message edited by: Administrator ]

 

[Administrator2]

SCOTT PAGE
Originally posted by David Plaisted:
If you think about the population genetics, the total number of genes will be huge because many mutations will occur at a very low frequency. I don't think the number of SNP's is a problem at all for assuming the human race is 300 generations old.

What is your justification for concluding that because there are many SNPs that the "...total number of genes will be huge because many mutations will occur at a very low frequency."


DAVID PLAISTED
If each human has an SNP about every 2000 base pairs then either (a) the human race is too old for literal Biblical creationism or (b) genetic diversity was already present in Adam and Eve (4 alleles of each gene etc.) or (c) there was an increase in mutation rates due to some environmental factor, possibly radiation or (d) we don't know the mutation rates or the frequency of SNP accurately or (e) some combination of the above. I'm still puzzled -- if each human has one SNP every 2000 bases on average then each human should have about 1.5 million total SNP (of 3 billion base pairs) just counting paternal or maternal chromosomes. The human genome project must have looked at at least 3 peoples' genomes which should have yielded about 4.5 million SNP on the spot, assuming 2 individuals don't share many SNP. Yet they are still struggling to get past 1 million?

The part about haplotype blocks and a young human race has to do with recombinations -- see my post about Mary, Bill, and Sue and maybe it will be clear. It's somewhat difficult to explain on a forum like this but if you insist I can try.


From froggie: In response to the claim that Dr. Wells made above, "beneficial mutations in developmental programs have not been observed,"
Another abstract has this to say:
Guided by x-ray crystal structures and molecular modeling, site-directed mutagenesis has been used to systematically invert the coenzyme specificity of Thermus thermophilus isopropylmalate dehydrogenase from a 100-fold preference for NAD to a 1000-fold preference for NADP. The engineered mutant, which is twice as active as wild type, contains four amino acid substitutions and an alpha-helix and loop that replaces the original beta-turn. These results demonstrate that rational engineering of secondary structures to produce enzymes with novel properties is feasible.

I'm getting "maxed out" by this thread and so you might need to prod me a little more to get a response -- anyway, about the above:
This article involves a human engineered protein obtained by replacing a sequence of 7 amino acids by a sequence of 13 amino acids and modifying 4 other amino acids. This is a _lot_ of mutation and it is highly unlikely that this could occur naturally. (Not that I dispute your general point that mutations can be beneficial.)


Originally posted by Zeratul:
"Genetic variation and linkage disequilibrium in 174 human genes"
2,549 SNPs were discovered in approximately 465 kb DNA sequence from 174 human genes with known genomic organization. DNA sequencing was performed on one chimpanzee and 82 unrelated individuals including African-Americans, Asians, European-Americans, and Hispanic Latinos.

How did that chimpanzee get in there?

(And how would it change the figures to take him out?)


ZERATUL
David: If each human has an SNP about every 2000 base pairs then either (a) the human race is too old for literal Biblical creationism or (b) genetic diversity was already present in Adam and Eve (4 alleles of each gene etc.) or (c) there was an increase in mutation rates due to some environmental factor, possibly radiation or (d) we don't know the mutation rates or the frequency of SNP accurately or (e) some combination of the above.

Since there is no evidence of (b) or (c), and multiple estimates of (d) are all of the same order of magnitude, then it does not seem like too much of a stretch to assume that (a) is the correct inference. This seems to me to be the scientific and objective way to approach this problem. That is not to say that some evidence may arise that might give support to one of the other explanations in the future. But based upon our current knowledge, genetics favors (a).


David: I'm still puzzled -- if each human has one SNP every 2000 bases on average then each human should have about 1.5 million total SNP (of 3 billion base pairs) just counting paternal or maternal chromosomes. The human genome project must have looked at at least 3 peoples' genomes which should have yielded about 4.5 million SNP on the spot, assuming 2 individuals don't share many SNP. Yet they are still struggling to get past 1 million?

The HGP would have needed to look at the entire genomes of 3 different people to identify millions of SNPs. I don’t believe that is what happened. I know that they looked at multiple people, but I think for the most part they were looking at different regions of the genome for different individuals. Someone please correct me if you have information to the contrary.


David: How did that chimpanzee get in there? (And how would it change the figures to take him out?)

I was wondering if you might bring that up. I was curious about that myself, but they wrote “2,549 SNPs were discovered in approximately 465 kb DNA sequence from 174 human genes with known genomic organization”. Note the reference to “human genes”. So apparently the chimp was not used for the SNP comparison. Also notice that the SNPs here occur on average every 182 base pairs.


DAVID PLAISTED
Since there is no evidence of (b) or (c), and multiple estimates of (d) are all of the same order of magnitude, then it does not seem like too much of a stretch to assume that (a) is the correct inference. This seems to me to be the scientific and objective way to approach this problem. That is not to say that some evidence may arise that might give support to one of the other explanations in the future. But based upon our current knowledge, genetics favors (a).

Well, there would _have_ to be _some_ genetic diversity in Adam and Eve, else we would all be clones (except for sex differences). That would not be very interesting, and it would also make it hard for humans to adapt to new conditions. It would also be easier for a plague to wipe everyone out.

I previously said that some environmental factor could have increased the mutation rate in the past. My understanding is that the mutation rate (in terms of mutations per unit time) increases with age. The large ages of the Biblical patriarchs (and the ages at which they had children) could also account for a higher mutation rate in the past. In addition, if there were many disasters in the past in a short time, there could have been an increased level of radiation. It's also possible that large quantities of radiation hitting the earth in the past could have led to extinctions and/or geological catastrophes.


SCOTT PAGE
If I recall correctly, 5 samples were used in the HGP by Celera alone. The 1 in ~2000 (I had read 1 in 2500 elsewhere) is, of course, an average. An average is calculated by dividing an observation by the total, and the average SNP distribution was extrapolated to the entire genome (hence the 1 in 2000 or whatever it is). In reality, SNPS are not spread so evenly, as there are areas of relatively high mutability (hot spots), conserved areas that resist accumulations of mutations (via selection), etc. If we align hot spots form two (or mnore) individuals, it should come as little surprise that they might 'share' some. [/I]


David: [/I]The part about haplotype blocks and a young human race has to do with recombinations -- see my post about Mary, Bill, and Sue and maybe it will be clear. It's somewhat difficult to explain on a forum like this but if you insist I can try.[/I]

You are assuming (so it seems) that during crossing-over, each chromosome is haphazardly 'broken up' and mixed. This is not so. Here, too, hot spots play a role, and would tend to negate your hypothetical analogy's point.


DAVID PLAISTED
You are assuming (so it seems) that during crossing-over, each chromosome is haphazardly 'broken up' and mixed. This is not so. Here, too, hot spots play a role, and would tend to negate your hypothetical analogy's point.

It was the authors of the Science article themselves who proposed a population bottleneck. They write (page 585):
"If, for some unknown molecular reason, some parts of the chromosome are less likely to recombine than others, some stretches of DNA will be conserved as blocks while others change rapidly across generations.

Population bottlenecks apparently contribute as well. ... "

Note also the phrase "some unknown reason," suggesting that they are not aware of a mechanism that would cause hotspots of recombination.


STEVE SCHAFFNER
Mutation rates have also been estimated for humans without making any assumptions about common ancestry. For example
Am J Hum Genet 1999 Dec;65(6):1580-7 estimates the nucleotide substitution rate to be 2x10-8 based on new mutations causing hemophilia. (They also get an estimate by comparing the gene sequence with that of the chimp, and find almost the same value, assuming the standard time since species divergence is correct.)


FROGGIE
David,
I admire your interesting thoughts and theories. Keep thinking and asking questions--that's the most important thing in science!


David The large ages of the Biblical patriarchs (and the ages at which they had children) could also account for a higher mutation rate in the past.

This could be true, but it's difficult to study. We just don't see people today that live to be 900 years old and are still able to reproduce. This indicates one of two things:
1) Humans were fundamentally different in the past in terms of age/breeding, and it is impossible (or at least very difficult) to study this phenomenon without more information

or

2) The first chapter of genesis is not a scientifically true account of natural history.

What evidence (real or theoretical) would support either of these options?

Could we extrapolate what we know about, say, 15-year-old moms and 50-year-old moms and use that information to make predictions about your theory, if #1 is correct?


In addition, if there were many disasters in the past in a short time, there could have been an increased level of radiation. It's also possible that large quantities of radiation hitting the earth in the past could have led to extinctions and/or geological catastrophes.

Again, can you think of ways to test this? Assumably, this large amount of radiation would have no doubt left its mark in other ways. For example, other organisms, or evidence in geology.

Again, what real or theoretical evidence would support or refute this theory?

What types of evidence do you think would be valid to answer these questions?


STEVE SCHAFFNER
Originally posted by wehappyfew:
They mapped the human genome. They constructed a "standard" genome - composed of the base pairs found in the majority of the test subjects. SNPs are defined as the differences from that standard. On average, any human will differ from the "standard" sequence at about 1 in a few hundred base pairs. (SNP fact sheet)
Any 2 people differ by 1 in 1000, according to froggie's sources, while differing from the "standard" by 1 in a few hundred. So can we infer that any 2 people will share about 2/3rds of their SNPs?

This is getting a little confused.
First, the Human Genome Project produced a sequence that's a mosaic of different people's DNA; in any region, it represent just one chromosome from one individual (and, in fact, about 70% of the total is one a single person from upstate New York).

Second, the discussion of SNPs has been confusing, at least to me. If you compare two chromosomes (one from Joe and one from Bob, for example), they will differ on average by 1 base every 1300. Of these differences, 80% or 90% are differences that are common in the population (i.e., they are polymorphisms). The bulk of polymorphisms (especially the most common ones) are common to most human populations. The total rate of SNPs (i.e., the rate you find if you compare lots and lots of chromosomes) is roughly one in a hundred bases.


Originally posted by David Plaisted:
It was the authors of the Science article themselves who proposed a population bottleneck….

What you're quoting isn't actually a Science article -- it's a news report in Science, so it's not necessarily a perfectly accurate reflection of the work in question.

It is true that the mechanism that lies behind hotspots of recombination is not well understood (although there are some general ideas that make sense), but the fact recombination does occur in hotspots is very well established in other organisms (especially yeast). So it's not exactly a novel or unlikely possibility that something similar happens in humans.

Furthermore, additional study has made it much more unlikely that population bottlenecks could be the cause of the long-range correlation you're describing.
The current conclusion of the study is that "simulations indicate that non-uniform recombination at a fine scale can readily explain these patterns, while changes in the historical size and substructure of the ancestral population are unlikely to constitute an adequate explanation".


ZERATUL
David: Well, there would _have_ to be _some_ genetic diversity in Adam and Eve, else we would all be clones (except for sex differences). That would not be very interesting, and it would also make it hard for humans to adapt to new conditions. It would also be easier for a plague to wipe everyone out.

I guess technically if Eve was made from Adam, then I guess they were clones. But, nobody’s arguing that they had no genetic diversity. I would assume they each had 2 (not 4) alleles per gene like the rest of us. Maybe I misunderstood what you were saying. I thought you were proposing that each had 4 alleles per gene. I address this below.

Let’s assume that they have DNA with a maximum amount of diversity (e.g., like an Aborigine and an Eskimo), but essentially the same as the rest of us. Their children wouldn’t be clones. If you look at a family with 10 children, some of them look alike but they are not clones. Now, during the next generation, when brothers and sisters had children together, it’s true that you wouldn’t have an influx of new genetic material. You would get a couple of new genes each generation due to mutations, so diversity would VERY SLOWLY arise. It doesn’t matter how much diversity Adam and Eve had, it is easy to show that UNLESS mutation rates were 3 orders of magnitude higher in the past, then 300 generations is not enough time to get the genetic diversity we have today.

If you want to propose an alternative, I would urge you to think it through and present it. Just saying that Adam and Eve could have each had 4 alleles is a little weak, in my opinion. Present some evidence. Propose a falsification test. Could we maybe expect to find an ancient human (in a peat bog, maybe, or frozen on a mountain) that might still have 4 alleles per gene? Is there some way that you can think of to support your position without resorting to miracles? If not, consider the possibility that you are wrong.

Don’t feel bad if you can’t refute the argument. Fred Williams was pinned on this at OCW and after much hand-waving he resorted to miracles (directed mutations). But, if you can’t come up with a pretty good alternative explanation, then I nominate this argument for your web page as one of “The Ten Strongest Evidences for Evolution”. http://www.cs.unc.edu/~plaisted/ce/evidences.html
You know the page; it is currently blank. If you disagree that this is a strong argument, then you should be able to refute it. If you agree that it is a strong argument, then you should probably list it on your web page, which currently implies that there are no strong evidences for evolution.


JOHN PAUL
Where did you get the notion that directed mutations equate to miracles?


DAVID PLAISTED
Originally posted by Steve Schaffner:
Second, the discussion of SNPs has been confusing, at least to me. If you compare two chromosomes (one from Joe and one from Bob, for example), they will differ on average by 1 base every 1300. Of these differences, 80% or 90% are differences that are common in the population (i.e., they are polymorphisms). The bulk of polymorphisms (especially the most common ones) are common to most human populations. The total rate of SNPs (i.e., the rate you find if you compare lots and lots of chromosomes) is roughly one in a hundred bases.

Before dealing with the other issues, I want to get this technical point straight. From this quote, I infer that there are "high frequency SNP" (in terms of what percent of the population they occur in) and "low frequency SNP."
What's the typical frequency in the population of a high frequency SNP, and how many of them are there altogether? Likewise for low frequency SNP.


DAVID PLAISTED
It never entered my mind that Adam and Eve could each have 4 alleles. I meant 2 for Adam and 2 for Eve.


ZERATUL
Where did you get the notion that directed mutations equate to miracles?

The reason that I consider directed mutations in the case of Adam and Eve a "miracle" is because there is absolutely no evidence of them. They were invoked merely as a way out of a very difficult problem. If you don't like the word "miracle", then call it ad hoc.


Originally posted by David Plaisted:
It never entered my mind that Adam and Eve could each have 4 alleles. I meant 2 for Adam and 2 for Eve.

My apologies. I have seen Creationists propose that Adam and Eve had some "super genome" with more than 2 alleles per gene. But, if you assume just 2 alleles per gene, the problem still stands with too few generations to get the required diversity.


STEVE SCHAFFNER
Originally posted by David Plaisted:
Before dealing with the other issues, I want to get this technical point straight. From this quote, I infer that there are "high frequency SNP" (in terms of what percent of the population they occur in) and "low frequency SNP." What's the typical frequency in the population of a high frequency SNP, and how many of them are there altogether? Likewise for low frequency SNP.

Let's start with observed SNPs. Among the TSC SNPs (the ones that were introduced near the beginning of this topic), the breakdown is roughly as follows. Approximatly 5% were never SNPs to start with (false positives); we'll ignore those. For any given population examined (these include Europeans, Africans and East Asians), roughly 20% of the remainder are monomorphic (have only one form) or are too rare to detect in ~100 chromosomes. 20% have a population frequency of between 0% and 10%, 15% between 10% and 20%, 15% between 20% and 30%, 15% between 30% and 40%, and 10% between 40% and 50%. (More precise value depend on population: Africans have fewer monomorphic SNPs than either Europeans or Asians, for example.)

Common SNPs are much more likely to have been discovered by TSC, however, so the real distribution in the population is much more heavily weighted toward rarer SNPs. That is, if you look at everyone, you will discover many more rare SNPs than common ones -- but of course you'll see the common ones much more often. I'd guess that TSC discovered something like one eighth of 50% SNPs, and only one four-hundredth of 1% SNPs.

[ January 21, 2002: Message edited by: Administrator ]

 

[Administrator2]

JOHN PAUL
The reason that I consider directed mutations in the case of Adam and Eve a "miracle" is because there is absolutely no evidence of them.

I take that to mean there is no 'experimental' evidence for them. Just like there is no 'experimental' evidence for endosymbiosis, abiogenesis, and mother nature together with father time and some as yet unknown natural process could account for all the diversity of life we observe today.

Recombinations happen- fact. Recombinations along with copying errors could account for the the alleles we observe today, especially if the original male & female pair (Adam & Eve) did indeed have 4 alleles per locus.


FROGGIE
I was wondering if there is any creationist literature that discusses this allele & recombination idea. I really don't have time to sort through a discussion. I want to see some DATA!


DAVID PLAISTED
Originally posted by Steve Schaffner:
It is true that the mechanism that lies behind hotspots of recombination is not well understood (although there are some general ideas that make sense), but the fact recombination does occur in hotspots is very well established in other organisms (especially yeast). So it's not exactly a novel or unlikely possibility that something similar happens in humans.

Furthermore, additional study has made it much more unlikely that population bottlenecks could be the cause of the long-range correlation you're describing.
The current conclusion of the study is that "simulations indicate that non-uniform recombination at a fine scale can readily explain these patterns, while changes in the historical size and substructure of the ancestral population are unlikely to constitute an adequate explanation".

The result about haplotype blocks was unexpected. If it could be explained by irregularities of recombination, then they should have taken this into account before discovering the small number of blocks. Thus the result should not have been a surprise. The fact that it was a surprise shows that it is not a consequence of what is known about recombination hotspots (or cold spots, which is essentially the same thing) and thus it is still unexplained.

But this pattern would be expected if there was a recent creation or a severe bottleneck -- starting with just a few copies of each chromosome (say chromosome 1) in the population, in a small number of generations each individual would have large stretches of chromosome 1 that came from one of these few ancestors. Thus nearby bases on different people today would tend to be correlated. The recent creation scenario of course does not rule out irregularities of recombination.

Given evolutionary assumptions, it may be unlikely that the pattern of haplotype blocks could be explained by a population bottleneck, but it does not seem so given creationary assumptions. One could have a severe bottleneck with just a few people either at the creation or after the flood; in either case the SNPs might already be present, either as diversity at the start or generated by higher mutation rate due to some environmental factor.

Also, from population genetics, what kind of a population bottleneck would lead to a genetic diversity of one in 1000 base pairs? This means that any two genes would have a common ancestor some number of generations ago -- I think 25,000 generations would produce this diversity at a mutation rate of 2 * 10^-8, right? By population genetics the population must have been about 25,000/2 for a long time (25,000 generations) to bring this about?
Is that plausible? My view is still that the creation was much more recent than that.


FROGGIE
David P,
Could you please explain what this is: "haplotype block phenomenon" and preferably link me to an article or web site???
Thanks a bunch,

I did a quick pubmed search. Is this the haplotype block stuff you are talking about?

Immunol Rev 1999 Feb;167:275-304
Genomics of the major histocompatibility complex: haplotypes, duplication, retroviruses and disease.
Dawkins R, Leelayuwat C, Gaudieri S, Tay G, Hui J, Cattley S, Martinez P, Kulski J.
Centre for Molecular Immunology and Instrumentation, University of Western Australia, Queen Elizabeth II Medical Centre, Nedlands, Australia. cmii@cyllene.uwa.edu.au

The genomic region encompassing the Major Histocompatibility Complex (MHC) contains polymorphic frozen blocks which have developed by local imperfect sequential duplication associated with insertion and deletion (indels). In the alpha block surrounding HLA-A, there are ten duplication units or beads on the 62.1 ancestral haplotype. Each bead contains or contained sequences representing Class I, PERB11 (MHC Class I chain related (MIC) and human endogenous retrovirus (HERV) 16. Here we consider explanations for co-occurrence of genomic polymorphism, duplication and HERVs and we ask how these features encode susceptibility to numerous and very diverse diseases. Ancestral haplotypes differ in their copy number and indels in addition to their coding regions. Disease susceptibility could be a function of all of these differences. We propose a model of the evolution of the human MHC. Population-specific integration of retroviral sequences could explain rapid diversification through duplication and differential disease susceptibility. If HERV sequences can be protective, there are exciting prospects for manipulation. In the meanwhile, it will be necessary to understand the function of MHC genes such as PERB11 (MIC) and many others discovered by genomic sequencing.

Also--I did find a reference that you posted DP,
"Science vol 293 27 July 2001 pp. 583-5." I'll go down the hall, grab that issue, read the article, and get back to you. Way to keep me learning, guys!


DAVID PLAISTED
Froggie, See Science vol 293 27 July 2001 pp. 583-5, partially quoted in one or two earlier posts. I don't know if this is the same concept as in the article you found by a search. I think the Science issue has another article about it, too.


ZERATUL
John Paul: I take that to mean there is no 'experimental' evidence for them.

Correct. They were invoked merely as an ad hoc solution to a difficult problem, because the alternate explanation, that humanity has been around for much longer than 300 generations, was unacceptable. You might as well just say, “God did it, because he can do anything”. Would you accept the following line of reasoning from a physicist?: “I know the Big Bang happened, because here we are”. Yet this is the same type of reasoning.

Regarding your comment on abiogenesis: This matter will never be resolved. First of all, I know that you are aware that it is totally separate from the ToE. Sure, some people might link it, but the word evolution implies that you had something to begin evolving from. But, even if man ever produces life from scratch in the lab, it won’t mean a thing. Because Creationists will just say, “See, it took a designer”. So, abiogenesis is nothing more than a red herring that Creationists like to bring up. You have your own origins problem, by the way, with the origin of the Designer.


John Paul: Recombinations happen- fact. Recombinations along with copying errors could account for the the alleles we observe today, especially if the original male & female pair (Adam & Eve) did indeed have 4 alleles per locus.

First of all, I will assume that the reference to the pair means that each had 2 alleles, for a total of 4. I want to be sure I understand this correctly. Correct me if this is not what you mean. Now, could you explain exactly how recombinations and copying errors could account for today's genetic diversity? I assume that you have been following the argument? You know that mutation rates have been estimated. Each of us could hypothetically trace our roots back 300 generations to Adam. That means that we had 300 generations to get today’s genetic diversity. Please explain in detail how this mechanism might work. I have heard a number of Creationists refer to such a thing, but nobody has ever been willing to provide details. I suspect that the devil is in the details. Also, I guess you would readily admit that such an increase in the number of alleles easily qualifies as an increase in information? If you disagree, please elaborate.


David: Zerutel says the SNP frequency should be on my list of evidences for evolution (currently empty). This argument from SNP frequency is not properly an evidence for evolution, but rather at most an evidence for the human race existing more than a few thousand years.

I will grant you that one. I actually thought about that after I posted it. But do you honestly believe that there is no evidence for evolution? Are there no arguments that trouble you?


DAVID PLAISTED
By the way, I just realized that the distribution of SNP is an impossibility according to the theory of evolution. The only way to get low genetic diversity as observed in the human race is an extended small population, about 12,500 people for at least 25,000 generations, or something like that. This would _not_ lead to an SNP every 100 or less bases and so many of them having frequencies in the 10 to 50 percent range. It would lead to a small amount of diversity in _every_ site on the chromosome, except for functional ones. I don't think anyone claims 99 percent of the genome is functional or that mutations only occur at one percent of the sites. Though the pattern of diversity may pose problems for creationism, it is a calamity for the theory of evolution. I am sure that geneticists in the know are aware of this problem and I am surprised that this bombshell has not hit the public yet. It was staring me in the face for so long and it wasn't until now that I saw it.

So the answer to this thread is: Genetics is definitely an evidence in favor of creationism, at least in the sense of posing more problems for evolution than creation.

Will be interesting to look at other organisms and see if they have a similar SNP pattern. Might have interesting implications.


FROGGIE
In regards to your last post: ????? I sure hope you aren't assuming that SNPs are the only variation between humans' DNA. You are also forgetting that many SNPs are generated, and they are harmful, and the organism dies.

Besides, the main evidences supporting evolution are the similarities. Yes, 98-99% of our genome is the same as in a chimp. What does that say about your amazing revelation? Just a handy coincidence?


By the way, I just realized that the distribution of SNP is an impossibility according to the theory of evolution.

Hey can I borrow $50 when you win the million dollar Nobel Prize? I have a bachelor's degree in molec biology, and the SNP papers I have read over the last several days are very complex and not always easy to understand. I find it hard to believe that all of a sudden you understand it better than thousands of researchers who have been studying the stuff for decades. But--I could be wrong. Publish your stuff in science or nature, and I'll be waiting for that Nobel laureate speech. . .

SNPs are, I think, the most stable form of mutation (or at least a very stable form), therefore not as affected by bottlenecks or other weird evolutionary occurences. For instance, it is difficult to use gene duplications and transversions as time predictors, because while these genetic phenomenon provide ample evidence for evolution, they affect variable amounts of the genome (some gene duplications affect 100 bp, others affect thousands, which makes the math a bit complex!) and it is difficult to draw time-scale conclusions from them. SNPs, however, are one base at a time, and assumably you can use random mutation math to predict how many SNPs we'd get over time with various hypotheses of how many generations we have been here. And from all the studies I have read, there is nothing that sticks out as clear evidence AGAINST evolution.

Back to that science article that you claim contradicts my above statement:

Well I read that article you mentioned. Unfortunately it’s a summary from a conference, and included no references or data. It did mention scientists’ names, though, so I was able to find some original research articles on the subject of SNPs and haplotype maps.

First some stuff from the article you read. What I gathered from it was that the number of SNPs was not surprising; rather the surprise was in the patterns of inheritance of SNPs. For instance, let’s say scientists have identified SNP #1, 2, 3, and 4, with variations a, b, and c for each loci. They probably expected these four to be more randomly distributed in the population (like I have type a at loci 1, type c at loci 2, etc. . .and you have type b at loci 1, type a at loci 2, etc). What they found, however, is that certain SNPs are found with other SNPs. Like finding patterns a and b associated with 1 and 2 in a certain population.

Haplotypes are simply long stretches of DNA—including perhaps as many as 100,000 bases—at a given location on a chromosome. To their surprise, genome researchers have found that many such blocks come in just a few different versions, a discovery that should simplify the search between DNA variations and complex diseases...As several teams reported at the meeting, haplotype blocks are at least 10 times longer than predicted, and there are a relatively small number at each chromosomal position...No one is sure yet why the genome is so blocky, but geneticists mention two candidate explanations.

The first explanation is unequal recombination. That is, certain parts of the chromosome do not recombine as much as other parts, so that “some stretches of DNA will be conserved as blocks while others change rapidly across generations.” Note the author mentions here that there are still parts of the genome that are rapidly changing across generations.

The second explanation is possible population bottlenecks. “there is a greater diversity of haplotypes in people in Africa, where humans first arose, than in other populations. In addition, descendants of people who settled in Asia carry a somewhat different set of haplotypes from those who settled Europe.”

It does not give time frames for these splits, but one can assume that the researchers are referring to the accepted time frame for human evolution. Note what the article doesn’t say: It doesn’t really mention evolution much at all, except for the above quote. Most of the article focuses on relevance in the medical community for finding diseases.

Summing up the meeting, Collins said that there was a “consensus” that the “project would have considerable medical value” and is worth pursuing.

I find it strange that if these results were indicative of a 6000 year old population versus a 50-100 thousand year old population, this fact would have been addressed. Indeed, the researchers would have most assuredly pointed it out, and probably assumed that the analysis was flawed. Any data generated that contradicts mainstream science is not usually immediately accepted by the whole conference as a “project with considerable... value.”
Indeed, if the data somehow proved evolution wrong, they would have probably focused on that. But I could be wrong!

I found another paper addressing this topic. “A high-resolution genetic map of the familial Mediterranean fever candidate region allows identification of haplotype-sharing among ethnic groups.” Genomics, 1997 Sept 15;44(3):280-291.

The researchers are studying a disease called FMF, or familial Mediterranean fever. Their conclusions state,
We observed a unique FMF haplotype common to Iraqi Jews, Arabs and Armenians and two other haplotypes restricted to either the Iraqi Jewish or the Armenian population. These data support the view that a few major mutations account for a large percentage of the cases of FMF and suggest that some of these mutations arose before the affected Middle Eastern populations diverged from one another.

I am going to try & get that article and see what the current time frame is thought to be for these population divergences. If they found something radically different from the current model of human evolution, again, I think it would have been addressed. Again, I could be wrong.

[ January 21, 2002: Message edited by: Administrator ]

 

[Administrator2]

DAVID PLAISTED
Let me explain what the problem is. According to my understanding of population genetics, some mutations fix (that is, approach a frequency near one in the population so almost everyone has it), some almost fix, etc. But the number that fix is very small (assuming neutral mutations), the number that almost fix is somewhat larger, etc. So according to population genetics, we should find only a small number of SNP with a high frequency in the population, but as we look at SNP with smaller frequency, they should get more abundant. Almost all SNP should have a frequency of 1/100 or slightly larger, which is the cutoff for being considered an SNP. And this is the assumption I initially made when I assumed that SNP were not a problem for a recent creation.

However, in fact, there are _way too many_ high frequency SNP to be permitted by population genetics. This is why I was initially so confused by this discussion.

Anyway, this stuff is very slippery, so I encourage you to ask someone who is familiar with this field if the distribution of SNP can be explained by population genetics.


To Zeratul: Reducing the population for a short time will probably not reduce the genetic diversity, as long as there is still a reasonable number of alleles left in the population. But increasing the mutation rate will increase genetic diversity.
To reduce genetic diversity you have to reduce the population size for a long time or reduce it very drastically (to say just 2 people, or something like that). Thanks for the question.


MESK
It never entered my mind that Adam and Eve could each have 4 alleles. I meant 2 for Adam and 2 for Eve.

I'm sure this has been mentioned before, but if Eve was derived from Adam's rib, wouldn't she have been genetically identical to him? Is there any Biblical justification for suggesting otherwise?
And of course, if Eve was genetically identical to Adam then the maximum initial number of alleles at each locus is reduced to two.


ECORI
is there really only 300 generations between us and adam and eve?
just curious, how many generations are between us and noah's kids? the reason i ask is because the flood "bottleneck" would reduce the number of alleles down to between 8 and 10 for each gene.


STEVE SCHAFFNER
David Plaisted: See Science vol 293 27 July 2001 pp. 583-5, partially quoted in one or two earlier posts. I don't know if this is the same concept as in the article you found by a search. I think the Science issue has another article about it, too.

Most of the research that the Science story refers to has not been published yet. Some has, however. The October issue of Nature Genetics has three articles on block-like haplotype structure; see the articles by Jefferys et al., Daly et al., and the one who's last author is Todd. These all report detailed studies of the structure of particular regions. There was also David Reich's paper in Nature (Nature. 2001 May 10;411(6834):199-204.) which did not look at haplotype structure, but which did show that correlation between alleles extends much farther than previously thought.

The unpublished work goes further by showing that haplotypes are a common feature of the genome, and not restricted to a few areas. The studies that I know of (which are the onoes Eric Lander was referring to in the Science report) are one by the Sanger Center, looking at SNPs across chromosome 22, and two by the Whitehead Genome Center, one looking at haplotypes in 50+ regions throughout the genome, the other looking correlations in SNP density in the whole genome.

Originally posted by David Plaisted:
Let me explain what the problem is. According to my understanding of population genetics, some mutations fix (that is, approach a frequency near one in the population so almost everyone has it), some almost fix, etc. But the number that fix is very small (assuming neutral mutations), the number that almost fix is somewhat larger, etc. So according to population genetics, we should find only a small number of SNP with a high frequency in the population, but as we look at SNP with smaller frequency, they should get more abundant. Almost all SNP should have a frequency of 1/100 or slightly larger, which is the cutoff for being considered an SNP. And this is the assumption I initially made when I assumed that SNP were not a problem for a recent creation.

However, in fact, there are _way too many_ high frequency SNP to be permitted by population genetics. This is why I was initially so confused by this discussion.

There's no problem for evolution here. The number of observed SNPs is comparable at low and high frequencies. Since you are much more likely to observe a high frequency than a low frequency SNP in a survey, however, the number of actual SNPs is much higher for low frequency SNPs. (I tried to explain this yesterday; evidently I wasn't clear.) The distribution that has been observed is just about what one would expect for a constant-sized effective population of around 10,000. To the extent that's there has been any discrepency, it has been in the opposite direction to David's suggestion above: there is a trend toward too many low-frequency SNPs, not too few. Too many for a constant-sized population, that is -- an excess of low-frequency SNPs is a sign of a population expansion, which of course we know has occurred (there are considerably more than 10,000 breeding humans in the world, and have been for some time).

The frustrating thing about SNP frequency data for evolutionary studies has been that they haven't been precise enough to answer interesting questions about population. There is nothing about them that suggests any kind of fundamental problem with evolution. (On the contrary -- I can't think of any coherent way of understanding them that doesn't include evolution.)


ZERATUL
by ecori:
is there really only 300 generations between us and adam and eve?
just curious, how many generations are between us and noah's kids? the reason i ask is because the flood "bottleneck" would reduce the number of alleles down to between 8 and 10 for each gene.

I have run a computer simulation of this before. If I recall correctly, there would be 200-220 generations between us and Noah. What I found by running the simulation is that you could actually generate a large number of alleles per gene in today's population, but only by assuming a mutation rate orders of magnitude higher than what is currently observed. Since there is no evidence that this ever took place, Creationists are left with a dilemma.


STEVE SCHAFFNER
by David Plaisted:
The result about haplotype blocks was unexpected. If it could be explained by irregularities of recombination, then they should have taken this into account before discovering the small number of blocks. Thus the result should not have been a surprise. The fact that it was a surprise shows that it is not a consequence of what is known about recombination hotspots (or cold spots, which is essentially the same thing) and thus it is still unexplained.

This does not follow. Almost nothing was known about the fine-scale distribution of recombination in humans until the last year or two, so no one knew what to expect. Discovering that much of human recombination occurs in hot spots is not surprising if you happen to have been keeping up with yeast genetics (yeast geneticists and human geneticists do not talk all that much). Discovering that recombination hot spots produce haplotypes is more unexpected, partlly because people hadn't been thinking much about it, and partly because population geneticists are used to looking at data from fruit flies and yeast, which have such large effective populations that haplotype blocks are broken down by recombination even with hotspots.

In any case, whether the result was unexpected or not, current evidence is quite strong that clustered recombination is the mechanism that generates the haplotype blocks. Look at the Jeffreys paper in the October issue of Nature Genetics. They identified haplotype blocks, and then demonstrated that their boundaries corresponded precisely to hot spots of recombination by observing the recombination in sperm. It's a beautiful piece of work.


But this pattern would be expected if there was a recent creation or a severe bottleneck -- starting with just a few copies of each chromosome (say chromosome 1) in the population, in a small number of generations each individual would have large stretches of chromosome 1 that came from one of these few ancestors. Thus nearby bases on different people today would tend to be correlated.

The problem (or rather, a problem) with your scenario is that you will get blocks that are too big. Even though haplotype blocks are larger than expected, there are still a lot of them on each chromosome (> 1/70 kb, probably much more), and lots of recombination has occurred between each block. We know the rate of recombination in humans -- it's about one crossover per chromosome arm per meiosis -- and it's easy to calculate that there must have been, at an absolute minimum, four or five thousand generations of recombination to produce the pattern we see.


Also, from population genetics, what kind of a population bottleneck would lead to a genetic diversity of one in 1000 base pairs? This means that any two genes would have a common ancestor some number of generations ago -- I think 25,000 generations would produce this diversity at a mutation rate of 2 * 10^-8, right? By population genetics the population must have been about 25,000/2 for a long time (25,000 generations) to bring this about? Is that plausible?

Yes, that's about right. (The actual population would be somewhat larger than the effective population, but it's the right order of magnitude.) And yes, it's perfectly plausible; it's pretty much the standard model for human population genetics. Humans have a rather low diversity, and hence small ancestral population, but not implausibly so. Chimps have about three times as much diversity; cheetahs have far less.


DAVID PLAISTED
by Steve Schaffner:
The frustrating thing about SNP frequency data for evolutionary studies has been that they haven't been precise enough to answer interesting questions about population. There is nothing about them that suggests any kind of fundamental problem with evolution. (On the contrary -- I can't think of any coherent way of understanding them that doesn't include evolution.)

We could do the calculation for sections of the genome that have been studied in detail, to see if the observed pattern of SNP frequencies corresponds to the laws of population genetics or not. Another possibility is to see what percentage of the total genetic diversity comes from SNP in the frequency range 25 to 50 percent. We should have found most of these SNPs, at least for parts of the chromosome. We can also estimate the genetic diversity, likewise. It looks to me that the percent of total genetic diversity coming from these high frequency SNPs is far too high to be permitted by the laws of population genetics.

When I said the data is inconsistent with the theory of evolution, that's not completely true. I think you can get the observed pattern if you start with a population with a genetic diversity of about 1/1000 and then have a_severe_ bottleneck, say to 5 or 10 people, followed by a few hundred generations of rapid population expansion.
But then this is essentially the recent creation scenario.


The problem (or rather, a problem) with your scenario is that you will get blocks that are too big. Even though haplotype blocks are larger than expected, there are still a lot of them on each chromosome (> 1/70 kb, probably much more), and lots of recombination has occurred between each block. We know the rate of recombination in humans -- it's about one crossover per chromosome arm per meiosis -- and it's easy to calculate that there must have been, at an absolute minimum, four or five thousand generations of recombination to produce the pattern we see.

I'm willing to accept irregularities (or should I say regularities) in recombination if there is evidence for it.
From your posts I assume there is about one recombination per 10^8 base pairs per meiosis. (But I saw a much larger figure one place.) In 300 generations we would have each person having blocks of about 300,000 base pairs coming from a single individual chromosome of 300 generations ago. Assuming a _very_ small population then, two people's blocks would tend to overlap in about 150,000 base pairs and so we would expect a correlation between bases for about that distance. For more people it would be somewhat less. This seems to be reasonably close to your figure of one haplotype block every 70,000 base pairs. If there are irregularities in recombination, that would make it even more plausible to create such haplotype blocks in 300 generations.

As for my other post, the percentage of total genetic diversity coming from frequent SNP should give us an estimate of population size. A higher percentage means a small population. I could try to estimate this figure myself but it would be better for a population geneticist to do it. My guess is that it leads to a _very_ small population.


FROGGIE
Dave,
Your last post is I think the whole crux of this debate. You said,
When I said the data is inconsistent with the theory of evolution, that's not completely true.

So we agree on something!


I think you can get the observed pattern if you start with a population with a genetic diversity of about 1/1000 and then have a _severe_ bottleneck, say to 5 or 10 people, followed by a few hundred generations of rapid population expansion

Or, alternatively, we could get the observed pattern if we assume that there were more than a few hundred generations, and the mutation rates haven't changed (I.E. rvolution).
We have asked you many times now--is there any other evidence that this huge bottleneck and then a new mutation rate occured on this earth? The evolutionary SNP theory has holes in it, sure (it is science we are talking about). But the thing is-accepting SNP rates as evidence for ToE does not require believing in some past unobservable event. Yours does. I think we have reached the limit of where we can go with this argument, unless you provide other evidence as requested above.

Yes you are correct Dave, I am a bit (ok a lot ) out of my league when talking about population genetics. That's why I was excited when John Paul brought up developmental biology. I don't think anyone has argued with any of the points I brought up in that post. Too bad-I know that field much better. Care to delve into that field with me?
Here's a starter question--how do creationists explain gene duplications? Hemoglobin is a good example to start with.

[ January 21, 2002: Message edited by: Administrator ]

 

[Administrator2]

SCOTT PAGE
David Plaisted :
"We could do the calculation for sections of the genome that have been studied in detail, to see if the observed pattern of SNP frequencies corresponds to the laws of population genetics or not. "

Which 'laws' of population genetics did you have in mind, and where can I read about these 'laws'?


DAVID PLAISTED
I'd suggest getting a text on population genetics. The talk.origins site has a pretty good survey. What you need to know is how neutral mutations behave -- it's not at all intuitive. If the population is N then the change that a neutral mutation will eventually "fix" (become nearly universal) in the population is about 1/N and the expected time for this is 4N generations (if I recall correctly). The chance that it will come to a frequency of 1/2 in the population is about 2/N I believe (taking about 2N generations on the average) and the chance that it will eventually reach a frequency of about 1/4 in the population is about 4/N et cetera. But this can be phrased much better than that but the math is somewhat involved.

So what this means is that one should expect SNP of frequency near 1/2 to be half as numerous (in terms of the number of them) as SNP of frequency near 1/4 et cetera, so low frequency SNP should by far dominate. And in fact each SNP can be caused by multiple mutations so you get the frequency of SNP as the _sum_ of a number of mutations, which should even out the distribution even more and bias it even more towards low frequency SNP. Thus the bulk of the genetic diversity should come from low frequency SNP. At least this is how it appears to me. But if N is very small (small population) you might get a larger contribution to the genetic diversity from very high frequency SNP, so the proportion of the genetic diversity from high frequency SNP can be used to estimate the population size. Of course a few hundred generations of expansion won't affect this proportion very much but this gives a snapshot of how small the population was at one time.


STEVE SCHAFFNER
So what this means is that one should expect SNP of frequency near 1/2 to be half as numerous (in terms of the number of them) as SNP of frequency near 1/4 et cetera, so low frequency SNP should by far dominate. And in fact each SNP can be caused by multiple mutations so you get the frequency of SNP as the _sum_ of a number of mutations, which should even out the distribution even more and bias it even more towards low frequency SNP.
Thus the bulk of the genetic diversity should come from low frequency SNP. At least this is how it appears to me.

I haven't tried to check the details of your calculation, but it's certainly right in its thrust. What I don't understand is why you think there's a problem with the SNP data. When small regions have been looked at with heavy coverage (i.e. looking at lots of chromosomes), they find most SNPs to be rare. For example, Hulushka et al. (it's in the July 1999 issue of Nature Genetics) found 60% of SNPs to be below 10% in frequency. The TSC data bear this out as well: they're heavily biased against rare SNPs, but find them even more often than they do common ones, which means there must be many more rare ones than common ones. Where's the discrepency?


DAVID PLAISTED
I haven't tried to check the details of your calculation, but it's certainly right in its thrust.
What I don't understand is why you think there's a problem with the SNP data. [/I]

[This post contains some errors. See my later posts. -- DP]

I'm sorry to admit that this subject is confusing me. I now think that even though fewer mutations reach a large frequency in the population, they take longer doing it, and so these effects tend to balance each other out. So one should expect roughly equal numbers of SNP of all frequencies in the population, right? And this seems to be what is observed except that there seem to be too many low frequency ones? This would indicate a rapid increase in the size of the human population, I think.

[from the next post by David:]
No I was right in the first post. Low frequency SNP should be much more common in the population. In the figures Steve gave earlier, he said:
"15% between 10% and 20%, 15% between 20% and 30%, 15% between 30% and 40%, and 10% between 40% and 50%"

It's true that common SNP are more likely to be discovered than rare ones, but one could at least look at some parts of the genome in detail to get exact figures for SNP there. The figures given above are not weighted at all towards rarer SNP. You would just need to look at a region of the genome in 20 people to get most of the 10 percent SNP. Also this quote from Steve suggests the same problematical distribution of SNP:

"If you compare two chromosomes (one from Joe and one from Bob, for example), they will differ on average by 1 base every 1300. Of these differences, 80% or 90% are differences that are common in the population (i.e., they are polymorphisms)."

Based on my initial confusion with SNP I also believe that the distribution is not as population genetics would expect. Anyway, it can be checked. I should check the July 1999 issue of Nature Genetics.

The problem is that the expected distribution of SNP is a "trademark" of a population produced by evolution, especially for an extended time (say 10,000 people for 20,000 generations). It looks to me like the distribution of SNP does not follow this pattern and so could not be produced by evolution. (I admit very rare SNP -- say under one percent -- may be very common but these were undoubtedly introduced more recently.)

Even if you just take a severe population bottleneck and pick 5 or 10 people from a population, the same general distribution of SNP should persist. So I am returning to my original view that the SNP data are not consistent with the theory of evolution (unless more precise figures show the expected pattern). The SNP distribution would have to be produced by SNPs present at the creation or that were produced by a high mutation rate for a short time, for whatever reason.


SCOTT PAGE
The talk.origins site has a pretty good survey. What you need to know is how neutral mutations behave -- it's not at all intuitive. If the population is N then the change that a neutral mutation will eventually "fix" (become nearly universal) in the population is about 1/N and the expected time for this is 4N generations (if I recall correctly).

Standard Kimura. I have a collection of his seminal works.

I'm not sure why you are conflating 'genetic diversity' with neutral mutations, of which most SNPs will be.

Last I knew, according to the laws of population genetics, the smallest bottleneck in human history, derived from mtDNA sequenbce analysis, was in the neighborhood of a few thousand individuals.


Even if you just take a severe population bottleneck and pick 5 or 10 people from a population, the same general distribution of SNP should persist. So I am returning to my original view that the SNP data are not consistent with the theory of evolution (unless more precise figures show the expected pattern). The SNP distribution would have to be produced by SNPs present at the creation or that were produced by a high mutation rate for a short time, for whatever reason.

If the SNPs were present at creation, by definition, they would NOT be SNPs. That should be fairly obvious. If they were produced by high mutation rates for a short time, what caused the rates to slow down?


DAVID PLAISTED
I'm not understanding the thrust of all of Scott Page's remarks -- but anyway, after some time to think this over, here are my conclusions:

Assuming almost all mutations are neutral, looking at just the SNP present in _one person_, one person should have roughly equal numbers of SNP in the frequency ranges 1/2 - 1/4, 1/4 - 1/8, 1/8 - 1/16 et cetera. That is, counting the SNP having these frequencies in the total population, equal numbers roughly speaking should appear in a given person. Now, the absolute numbers do not depend on the population size, only on the mutation rate. However, the lower range of frequency is of course lower (down to 1/N for a population of N) for larger populations, increasing the genetic diversity.

Anyway, even looking at the SNP present in just one person, we see that they will be biased towards low frequency SNP. Thus one cannot explain the apparent uniform distribution in the TSC SNPs by a measuring bias that favors discovering high frequency SNPs.

Looking at the SNPs present in a whole population, the bias is even stronger: twice as many in the 1/8-1/4 frequency range as in the 1/4 - 1/2 frequency range, twice as many again in the 1/16 - 1/8 frequency range, etc. The TSC figures Steve cited must have been taken from 100 chromosomes or more, since percentages down to about 1 %. Thus these figures should be _even more strongly_ biased towards low frequency SNP than the figures for just one person. Thus the uniform distribution of SNP in the range 1% to 50% is even more of a puzzle.

This distribution of SNP should not even be sensitive to population size or bottlenecks (at least in the frequency ranges we are discussing). Also, since there are so many sites on the chromosome being compared, there is a strong statistical basis for assuming that the distrubition should be according to theory. That is, the distribution should inidicate many more low frequency SNP than high frequency ones.

My basic insights in this analysis were obtained from the talk.origins site and other material I saw about population genetics, as well as email I received from a population geneticist. Steve Schaffner seemed to think the basic idea was OK too. It certainly could be given to a population geneticist for verification.

If one assumes a constant mutation rate then the observed pattern of SNP frequencies is inexplicable. However, if one assumes a rapidly decreasing mutation rate, then one might get such a uniform appearing pattern of SNP's, that is, a pattern such as Steve cited from the TSC data with roughly equal numbers of SNP in the frequency ranges 0-10%, 10-20%, et cetera. I did not at all set out to prove this but it just fell out of the data. In fact the data suggests that the mutation rate decreased by a factor near 100.

At any rate, from the SNP data I believe one can read off a history of the population of the human race, as well as a history of the changes in the mutation rate. It wouldn't surprise me if population geneticists are already looking at this subject and have already written papers and submitted them for publication. But if my conclusions are true, then either the data is inconsistent with evolution or else indicate a much higher mutation rate in the past, which also favors the recent creation model.

Editing correction: The data suggests that the mutation rate was about 10,000 times higher in the past.


STEVE SCHAFFNER
David Plaisted: No I was right in the first post. Low frequency SNP should be much more common in the population. In the figures Steve gave earlier, he said:
"15% between 10% and 20%, 15% between 20% and 30%, 15% between 30% and 40%, and 10% between 40% and 50%"
It's true that common SNP are more likely to be discovered than rare ones, but one could at least look at some parts of the genome in detail to get exact figures for SNP there.

One could indeed look in more detail. I gave you a reference yesterday to just such a study (the one by Hulushka et al.); it reported (as expected), that most SNPs were rare. Did you not see what I wrote?
[Ah, I see later that you did see the reference. Good.]

I should make clearer at this point why the TSC SNPs will not directly reveal the same pattern. The TSC SNPs were discovered by comparing a single chromosome (in a small region) with the reference sequence produced by the Human Genome Project. The probability of detecting a SNP of frequency p in such a single comparison is 2p(1-p). So for a 50/50 SNP, TSC had a 50% chance of detecting it, while for a 1/99 SNP, they had a 2% chance of detecting it. So the fact that they detected (roughly) equal numbers of 1% and 50% SNPs means that there must be roughly 25 times as many 1% SNPs as 50% SNPs, exactly in accord with standard evolutionary expectations. (In reality, the situation is slightly more complicated, because a fraction of the time the TSC did have multiple coverage (up to four or five fold), but this is a small correction, since the great bulk of the data had only single coverage.)

I should also mention that the TSC SNP discovery project, given that it was carried out as I've just described, had no way of determining the frequency of any of its SNPs. The frequencies that I provided (and that David quotes above) were determined by a second project, the TSC Allele Frequency project, which did not search for new SNPs, but simply measured the frequency of the previously detected SNPs in a larger sample of chromosomes (~100 chromosomes in each ethnic group studied).
The distinction between these two projects might be what has confused David. The results of the second project have not yet been published, but should appear within the next few months.

The problem is that the expected distribution of SNP is a "trademark" of a population produced by evolution, especially for an extended time (say 10,000 people for 20,000 generations). It looks to me like the distribution of SNP does not follow this pattern and so could not be produced by evolution. (I admit very rare SNP -- say under one percent -- may be very common but these were undoubtedly introduced more recently.)

To the extent that the TSC allele frequencies are causing head-scratching, it's because they show too many low-frequency alleles, not because they show too few.


DAVID PLAISTED
Thanks, Steve, that clears up a lot. I was hoping to delete my earlier post because it has some subtle mistakes, but since there have already been replies, I'll leave it in.

Here's the way the calculations should go: The number of mutations that reach a 1/4 to 1/2 frequency range should be about half as many as those that reach a 1/8 to 1/4 frequency range, but they should be in this 1/4 to 1/2 frequency range about twice as long, and should spread to about twice as many people (this factor I neglected). So a typical individual should have about twice as many SNP in the 1/4 to 1/2 frequency range as in the 1/8 to 1/4 frequency range, etc. This means that for one person, the distribution of SNP over all frequency ranges should be uniform, as it appears in the SNP data from 1 percent to 50 percent range. Thus there is no conflict with the theory of evolution. The large number of small frequency SNP should then indicate a rapid population growth, which is consistent with a recent creation anyway.

Now, in the population as a whole, the number of SNP in the range 1/8 to 1/4 should be twice as large as those in the range 1/4 to 1/2, et cetera, with a bias towards low frequency SNP. But since the figures given were from just one chromosome (I never would have imagined the figures were obtained this way), the bias towards low frequency SNP in the total population is irrelevant to the TSC data.

Another thing I misstated is the dependence on population size. It turns out that the number of SNP in a particular individual, that appear in the 1/4 to 1/2 frequency range overall, depends _both_ on the population size _and_ the mutation rate. Thus larger populations should have more SNP per person in this range.

Anyway, one can read off a history of population growth from the SNP data. The reason is that higher frequency SNP tend to be older, and give information on the population size at a much earlier time. I actually saw this fact stated in one of the references given in the earlier thread.


To the extent that the TSC allele frequencies are causing head-scratching, it's because they show too many low-frequency alleles, not because they show too few.

Without looking at many many chromosomes, it may be difficult to find out exactly what the frequencies of these low frequency SNPs are. But anyway, it's conceivable that they originated very recently, within several hundred generations, and then the large number of them might again indicate a faster mutation rate in the past.


I'd actually be interested to know how much genetic diversity there is on the Y chromosome of human beings.
(The parts that cannot recombine with the X, as some of it can, I understand.) Any genetic diversity there would have to arise after the creation, from a recent creation viewpoint. This could help to distinguish how much diversity was present at the creation and how much arose later, at least for creationists.


DAVEW
Adam had one Y chromosome, Eve had none. Even an "evolutionist" like me can figure that out.


DAVID PLAISTED
Thanks! Of course. I didn't ask that -- I asked how much genetic diversity existed at the creation, in total. The point is this: If there is a lot of diversity now in the Y chromosome, it had to originate since the creation. Thus from a recent creation viewpoint, there had to be a high mutation rate in the past. If there is hardly any diversity now in the Y chromosome, then there need not have been a high mutation rate in the past and so the diversity in the other chromosomes today must have already been present at the creation. According to evolutionary theory, the diversity in the Y chromosome today should be about 1/4 of that in the other chromosomes, I believe. But if the diversity in the Y is a lot smaller than that, this would indicate that some of the diversity in the other chromosomes was present at the creation. It would also be interesting to see how many SNP of various frequencies exist on the Y chromosome, because this could also tell us when this diversity originated, and when the SNP of various frequencies originated on the other chromosomes as well. If the Y chromosome has no high frequency SNPs, then this suggests that all these high frequency SNPs on other chromosomes originated from diversity present at the creation. One can also look at diversity in the Y chromosome within races to get information about when various kinds of diversity originated, since the races would originate somewhat after the Flood, in a recent creation viewpoint.


MESK
According to evolutionary theory, the diversity in the Y chromosome today should be about 1/4 of that in the other chromosomes, I believe.

Should it? I heard somewhere that the germ-line mutation rate in males is about four times higher than in females (due to the higher number of cell divisions in spermatogenesis compared to oogenesis). Wouldn't that result in higher diversity in the Y chromosome compared to autosomal chromosomes?


STEVE SCHAFFNER
The higher mutation rate in males leads to a higher diversity, while the smaller population of Y chromosomes leads to a smaller diversity. The numbers I remember for the male/female mutation rate ratio are around two (although it's not something I've researched); that would lead to a Y chromosome diversity 4/3rds that of the autosomes. The Y chromosome effective population is one fourth that of the autosomes, and possibly significantly less, if polygyny was common in the human lineage. The smaller population translates into a proportionally smaller diversity. (In the neutral theory with a constant-sized population, the mean time to the most recent common ancestor of two copies of a chromosome is 2N, where N is the population, and the number of polymorphisms is 4uN, where u is the mutation rate.) So the higher mutation rate only offsets the smaller population slightly.

To answer the David's question, the measured heterozygosity of the non-recombining Y is 1.5x10^-4, which is 20% of the value for autosomes. (This is in the February Nature TSC paper that started the previous topic.)
So it's in the range of evolutionary expectation -- especially is you add in selection, which will act more strongly on the Y than on autosomes.


[/b]MESK[/b]
OK, now it makes sense. Thanks.

OK, another ignorant question: how is it possible to talk about the "heterozygosity" of the Y chromosome, given that any individual contains at most one of them? What does heterozygosity actually mean in this context?


STEVE SCHAFFNER
Heterozygosity in this context means the probability of finding a sequence difference between a pair of chromosomes drawn randomly from the population. The meaning you're thinking of can be seen as a special case of this meaning.

[and a correction to his post above:]
Note: correcting for false positives in both Y and autosomes should push the value for Y down to around 15% of the value for autosomes.


It would also be interesting to see how many SNP of various frequencies exist on the Y chromosome, because this could also tell us when this diversity originated, and when the SNPf various frequencies originated on the other chromosomes as well. If the Y chromosome has no high frequency SNPs, then this suggests that all these high frequency SNPs on other chromosomes originated from diversity present at the creation. One can also look at diversity in the Y chromosome within races to get information about when various kinds of diversity originated, since the races would originate somewhat after the Flood, in a recent creation viewpoint.

I haven't seen a distribution of SNP frequency for the Y chromosome (I also haven't looked very hard), but there are certainly old variants (i.e. SNPs that are frequent and are found in a range of populations). See, for example, Nature Genetics 26(3), 358 - 361 (Nov 2000).
(They actually report haplotypes, not SNPs, but the haplotypes are largely constructed out of SNPs.)
Note that there's no evidence of a dramatically higher mutation rate in the human lineage, nor am I aware of a mechanism for such an increase that wouldn't leave other signatures behind.


DAVID PLAISTED
To answer the David's question, the measured heterozygosity of the non-recombining Y is 1.5x10^-4, which is 20% of the value for autosomes. (This is in the February Nature TSC paper that started the previous topic.)
So it's in the range of evolutionary expectation -- especially is you add in selection, which will act more strongly on the Y than on autosomes.

Thanks, I found that reference and looked it up after posting. Using the figure of 1.5 * 10^-4 for the diversity of the non recombining Y chromosome, the mutation rate needed to create this diversity in 300 generations would have to be about 6 times higher than 2 * 10^-8 or 1.2 * 10^-7, I think. If the figure for the Y diversity is really15 percent of the autosomal diversity instead of 20, and if we use 2.5 * 10^-8 instead as the mutation rate, to create this diversity requires a mutation rate 3 or 4 times higher than presently exists, assuming this diversity appeared in 300 generations, and assuming the Y chromosome mutates twice as fast (maybe this is too extreme).
Anyway, it's not a factor of 100 to 1000 increase in the mutation rate, but it is somewhat elevated. The rest of the diversity existing in humans would originate from diversity that was already present at the creation. The 20 percent of the diversity in the Y chromosome would correspond to 10 percent diversity in the other chromosomes, perhaps, which means that 90 percent or more of the existing human genetic diversity would originate from diversity that was present at the creation. In 300 generations, there would not be time for mutations to fix, so the population size would not affect the diversity originating since the creation.

It is tempting to think that the high frequency SNPs in autosomal chromosomes would all originate from diversity present at the creation, but even from a recent creation viewpoint this would not necessarily be so, considering the diversity present in the inhabitants of the ark.

The theory of neutral evolution predicts that the Y chromosome would have maybe 50 percent of the diversity of the general population, maybe somewhat less, while the actual figure is 20 percent, maybe 15 percent. Of course, this figure can be accounted for by various assumptions, but juggling the assumptions to fit the data is easy with the theory of evolution. Just about anything can be accomodated. How would you know if the theory were not true?


STEVE SCHAFFNER
I think a factor of two in the mutation rate is too high. The measurement of the ratio between male and female mutation rates looks pretty solid to me. (I'd love to see a creationist explanation for that measurement -- it's on p. 887 of the same Feb. 15 issue of Nature). I'd say the expected diversity for Y would be around 30 or 35% of the autosomes, and the observed is 15 to 20%. Not a significant difference from your values, in this context. Which is to say, diversity on the Y chromosome, assuming neutral theory, only dates from the last 50 or 100 thousand year.


The rest of the diversity existing in humans would originate from diversity that was already present at the creation. The 20 percent of the diversity in the Y chromosome would correspond to 10 percent diversity in the other chromosomes, perhaps, which means that 90 percent or more of the existing human genetic diversity would originate from diversity that was present at the creation. In 300 generations, there would not be time for mutations to fix, so the population size would not affect the diversity originating since the creation.

I don't follow the difference between the 10% and the 20%, but that's probably not important. If the bulk of human diversity dates from the creation (ignoring the Flood, for the moment), there are some rather odd features of that diversity. For example, SNPs show a strong bias toward occurence where there's a C and a G adjacent (a CpG, as it's known), and a weaker bias toward polymorphisms where the two alleles are both purines or both pyrimidines. The same biases occur in observed mutations. And, of course, in interspecies genetic differences. SNP density (the number of SNPs per 1000 base pairs) shows a strong correlation over distances of a few tens of thousands of base pairs, which is exactly what we would expect from an old population accumulating mutations, but which doesn't seem like an obvious feature to expect of created diversity. There are other problems as well -- regions of chromosomes that have more than 4 major, and quite different, haplotypes, for example. Or the presence of so much recombination, almost all of which seems to predate the divergence of African, Asian and European populations.

I think you've got a very tough row to hoe with genetics. (I do commend your attempt to make sense of it, however -- I've never encountered a creationist, YEC or OEC, who displayed any interest in coming up with a coherent understanding of genetics within creationism.)


DAVID PLAISTED
You say a factor of two in the mutation rate between males and females is too high. I saw a reference about this once -- the idea is that males may mutate quite a bit faster. Since Y chromosome spends all of its time in males and others half of the time, if males mutate a lot faster then the ratio could approach two. I don't have the refs handy however. Perhaps there is a range of possibilities.

You ask for a creationist explanation of why males mutate faster. I don't understand the question and don't see why this is a problem.

If the diversity on the Y is 1.5 * 10^-4 then there is about one difference between two people every 6600 base pairs, or one mutation every 13000 base pairs in this time. If males mutate twice as fast (maybe a little extreme) this is one every 26,000 bp assuming a normal mutation rate. In 300 generations there would be one mutation every 7.6 million base pairs, or a rate of 1.3 * 10^-7. The rate is 2.5 * 10^-8. However, on the earlier thread a reference was posted that said direct measurements yield a rate of 1 to 5 * 10^-8 and it could be substantially higher because this is measured in genes and does not measure mutations that cause death very early. This is from the talk.origins 29 evidences for macroevolution:

Background spontaneous mutation rates are extremely important for cancer research, and they have been studied extensively in humans. A review of the spontaneous mutation rate observed in several genes in humans has found an average background mutation rate of 1-5 x 10-8 base substitutions per site per generation. This rate is a very minimum, because its value does not include insertions, deletions, or other base substitution mutations that render these genes completely nonfunctional (Mohrenweiser 1994, pp. 128-129). Thus, the fit amongst these three independent sources of data is extremely impressive.

If you also consider that environmental factors could have played a role, this mutation rate does not seem extreme at all. Especially because long-lived patriarchs could have accentuated the male-female mutation difference.

You say the diversity has features (related to CpG etc.) suggesting mutations. How stongly do such features show up? If the diversity is a mixture of created diversity and mutation diversity, then there would still be some features of it that are characteristic of mutations.

Regions of chromosomes that show more than 4 different haplotypes (by the way I see you are getting the point very well, congratulations) might be explained by large scale mutations such as inversions or translocations or duplications. Also, if there was significant mutation before the flood and only a few people afterwards, then there could be more than 4 haplotypes.
I'm curious to know how you are sure there was so much recombination -- too much for a recent creation -- and why you feel this could not be explained by one or two severe population bottlenecks, down to just a few people, at the creation and Flood.

Before we know better the function of the non-coding DNA, it's difficult to speculate on what one should expect from created diversity.