Sanford and Carter: Allele Frequencies and a YEC Adam and Eve

[Joel_Duff (R. Joel Duff)]

Sometimes the errors are so large that it is tempting to think that we are missing something because “they simply couldn’t have missed this.” So we find ourselves feeling unsure when, in fact, the obvious criticism really is that obvious. I believe that is what we have here though I have only glanced at Sanford ICC paper. BTW, notice that they do include two references to Jeanson but they only tangentially use them early in the introduction. They don’t interact with Jeanson’s ideas. I think that is partially because it is hard to say that Jeanson has a model to interact with. Despite his insistence that he has a testable model other YECs don’t seem to find it useful to talk about and test.

[evograd (Blogging Graduate Student)]

@Joel_Duff

Sometimes the errors are so large that it is tempting to think that we are missing something because “they simply couldn’t have missed this.” So we find ourselves feeling unsure when, in fact, the obvious criticism really is that obvious.

Exactly, that really hits the nail on the head. Especially since I’m commenting outside my area of expertise, it’s nice to just get some reassurance that I’m not missing something obvious.

[swamidass (S. Joshua Swamidass)]

@evograd

I looked into this, and I was right. The Y-chromosome SNV mutation rate is estimated to be approximately 0.8x10^-9 mutations/bp/year.

@evograd this is the crux of Jeanson’s argument. Everything else is a distraction. He has an incorrect way of computing mutation rates. He uses this incorrect mutation rate, which is far too high, to estimate m-MRCA, and it ends up very recent. He ignores autosomal-MRCA and y-MRCA because he can’t pull out of a hat such an absurd mutation rate.

Without his mito-mutation rate he has nothing new to add.

[evograd (Blogging Graduate Student)]

Now I’m second-guessing myself again (third-guessing?).

In this 2016 article in ARJ, Jeanson draws a distinction between the AFS and the variants present in each individual:

Origin Eukaryotic Genotypic Phenotypic Diversity

To clarify, within the world-wide human population, over 84 million total SNV sites have been identified (1000 Genomes Project Consortium et al. 2015). Rare variants, by definition, represent most of these 84 million sites. Since common variants would be present at identical sites in a variety of different individuals, common variants would constitute the minority of sites—they show up frequently but add little to the total number of different sites. By contrast, within each individual, only 3.5–4.3 million SNVs exist on average, and the vast majority of SNVs (>80%) within a single individual are common variants (1000 Genomes Project Consortium et al. 2012, 2015). Thus, within each individual, >80% of the nuclear SNVs (80% by the “common variant” criterion; >98% by Fig. 3B) are due to inheritance of alleles that arose via fiat creation during the Creation Week in Adam and Eve, and a small but significant minority of nuclear SNVs within an individual are due to mutations since Creation.

This seems to suggest that I was right (yay?) earlier when I said:

Or am I mistaken in trying to compare these 2 things, because one is the AFS across a whole population while the other is the proportion of variants separating 2 individuals in a population?

Anyone else want to weigh in on this?

[swamidass (S. Joshua Swamidass)]

I am a minimalist.

For this reason, I would shy away from the AFS data. It is just not strong evidence. You risk muddying the waters, making it seem that all the evidence is debatable, just because this is.

[evograd (Blogging Graduate Student)]

@swamidass

@evograd this is the crux of Jeanson’s argument. Everything else is a distraction. He has an incorrect way of computing mutation rates. He uses this incorrect mutation rate, which is far too high, to estimate m-MRCA, and it ends up very recent. He ignores autosomal-MRCA and y-MRCA because he can’t pull out of a hat such an absurd mutation rate.

Without his mito-mutation rate he has nothing new to add.

I agree, although I’m still trying to figure out exactly how the autosomal TMRC4A is incompatible with the idea of “created heterozygosity” idea. Wouldn’t it come down to recombination rates etc? I don’t know, I’m not there yet.

[glipsnort (Steve Schaffner)]

@evograd

Third, while the AFS in terms of proportions of alleles with different frequencies in the population might be possible to get in their model of created heterozygosity, what about the actual number of different alleles? The more alleles you deem “originally created”, the smaller the proportion of “mutational alleles” becomes, flattening out the AFS.

To tie this point into Nathaniel Jeanson’s work, consider the proportion of SNPs required to be “originally created” versus the proportion required to have arisen by mutation. Figures 6b and 7 of Sanford et al’s paper suggests that between 30-60% of all SNPs (discounting the rare alleles) in extant human populations would have been the result of mutations in the last few thousand years. On the other hand, in chapter 8 of his book “Replacing Darwin”, Jeanson argues that “originally created” SNPs accounts for 99.6% of the variation in modern human populations, leaving just 0.4% of SNPs as the result of mutations (~15,000/4,000,000 - Figure 8.11 of the book). He does this because only around 15,000 mutations can separate the 2 most divergent living humans today given a 6,000-year timeframe, given current mutation rates.
I don’t see how Jeanson’s claim can be reconciled with Sanford et al’s simulations of the AFS. I agree with Sanford et al’s logic in how the originally created SNPs would have to spread over the AFS from their original distributions at a frequency of 25% or 50% in Adam and Eve to form the low, flat distribution in the AFS, and I don’t see how that’s compatible with the vast majority of SNPs being pre-existing. Or am I mistaken in trying to compare these 2 things, because one is the AFS across a whole population while the other is the proportion of variants separating 2 individuals in a population?

I haven’t read either Jeanson or this paper by Sanford, but I don’t see anything wrong with your reasoning. The genetic distance between two genomes (hopefully comparisons are actually being calculated between genomes and not between diploid individuals – the latter is unnecessarily complicated) is a different quantity than the AFS for the population, but they’re related. If the AFS is calculated as absolute numbers rather than a proportion, it’s straightforward to calculate the mean number of differences between genome copies (for biallelic variants with frequency f, it’s just 2f(1-f), summed over all of the variants).

[swamidass (S. Joshua Swamidass)]

@evograd

Without his mito-mutation rate he has nothing new to add.

I agree, although I’m still trying to figure out exactly how the autosomal TMRC4A is incompatible with the idea of “created heterozygosity” idea. Wouldn’t it come down to recombination rates etc? I don’t know, I’m not there yet.

Yes it comes down to recombination rates, and evidence of recombination, which we know very reliably and do not change very much at all.

[evograd (Blogging Graduate Student)]

@swamidass

For this reason, I would shy away from the AFS data. It is just not strong evidence. You risk muddying the waters, making it seem that all the evidence is debatable, just because this is.

I wouldn’t be using the AFS to argue for an older bottleneck though, I’m specifically trying to understand how the AFS discussed in Sanford et al. fits in with the idea of created heterozygosity, and where the “created variants” would show up on the AFS.

[evograd (Blogging Graduate Student)]

@swamidass

Yes it comes down to recombination rates, and evidence of recombination, which we know very reliably and do not change very much at all.

OK, I’ll keep looking into it, there’s a lot to try and understand in that “heliocentric certainty” thread.

[evograd (Blogging Graduate Student)]

See what I said a moment ago:

Sanford and Carter: Allele Frequencies and a YEC Adam and Eve

Now I’m second-guessing myself again (third-guessing?). In this 2016 article in ARJ, Jeanson draws a distinction between the AFS and the variants present in each individual: To clarify, within the world-wide human population, over 84 million total SNV sites have been identified (1000 Genomes Project Consortium et al. 2015). Rare variants, by definition, represent most of these 84 million sites. Since common variants would be present at identical sites in a variety of different individuals, common variants would constitute the minority of sites—they show up frequently but add little to the total number of different sites. By contrast, within each individual, only 3.5–4.3 million SNVs exist on average, and the vast majority of SNVs (>80%) within a single individual are common variants (1000 Genomes Project Consortium et al. 2012, 2015). Thus, within each individual, >80% of the nuclear SNVs (80% by the “common variant” criterion; >98% by Fig. 3B) are due to inheritance of alleles …

What he says makes seems to make sense.