I'd be grateful if you could address my comments on clips from our post below. I must be being thick because, although i think i understand - and appreciate your argument and criticism of Bekewell et al, I can't see where you get he figures from and how they support your argument. Thus:

p-ter says: “The power of this test to detect selection is contingent on finding an excess of amino-acid changing substitutions in a lineage. So, what could alter said power? First, it’s clear that a single selected site will alter the ratio very slightly, two selected sites will alter it a little more, three even more etc. So, the more selective fixations that occur in a gene, the more power the test will have to conclude for selection. On the other hand, take the number of synonymous substitutions - if there are more of these, the levels of ‘noise’ are elevated relative to the levels of ‘signal’, and there is lower power to conclude for selection.”

Another way of saying this is that if the number of synonymous substitutions is high relative to the number of non-synonymous substitutions the ratio Ka/Ks will be lowered - forcing a (possibly erroneous) conclusion that no positive selection had occurred.

He continues: “There is a major difference between historical human and chimpanzee populations that alters the power of the test in the two lineages; indeed the authors mention this difference without really grasping why it discounts their conclusions. That difference is population size. Humans have historically had a smaller effective population size than chimps and, as the authors note, natural selection is more efficient in a larger population. Thus, advantageous alleles can be pushed to fixation with greater probability, while neutral or deleterious alleles are fixed at a lower rate. So, smaller populations should have overall higher levels of substitution (assuming positively selected changes are a minority of all fixations). This is exactly what is seen in the data - humans have 30,083 synonymous fixations and 19,000 non-synonymous fixations, while the chimp has 29,644 and 17,701 respectively.”

I can’t see where you get these figures from in the paper or how they support the argument. After all, if larger populations push advantageous alleles to fixation more efficiently than deleterious or neutral alleles, and this method only detects alleles that HAVE been driven to fixation, one can immediately see where the bias lies - there will be more noise in the human data and a depressed conclusion for positive selection. I don’t understand how these figures you quote back this understandable conclusion up and lead to your conclusion below.

“These changes in the rates of allele fixations should lead to a weaker signal of selection in humans, and thus less power to detect it. It’s no surprise, then, that the authors find less selected genes in humans than in chimps. Even if the number of selected genes were the same, the relatively stronger signal of selection in chimps should produce exactly the same result.”

Another way of saying this is that if the number of synonymous substitutions is high relative to the number of non-synonymous substitutions the ratio Ka/Ks will be lowered - forcing a (possibly erroneous) conclusion that no positive selection had occurred.

yes.

I can’t see where you get these figures from in the paper or how they support the argument.

from table 1. it's just a bit of evidence that more fixations in all classes of mutation have occurred along the human lineage, as would be expected given a lower effective population size in humans.

After all, if larger populations push advantageous alleles to fixation more efficiently than deleterious or neutral alleles, and this method only detects alleles that HAVE been driven to fixation, one can immediately see where the bias lies - there will be more noise in the human data and a depressed conclusion for positive selection.

yes. this method detects genes where multiple amino-acid changes have been driven to fixation. since a given gene under recurrent selection in humans will have fewer fixed adaptive changes than chimps, there is more "noise" in the human data and less power to conclude for selection.

that's what I think is the problem with this paper-- it assumes their test for selection has precisely the same power to detect selection in humans and in chimps, which is highly doutbtful.

that's what I think is the problem with this paper-- it assumes their test for selection has precisely the same power to detect selection in humans and in chimps

Saying that's "the problem" with the paper neglects all the other problems. Not only does dn/ds suck balls as a method for detecting selection, but, when looking as such closely related species, how can you get by ignoring the intraspecific polymorphism? How many of the "fixed differences" in this paper are actually segregating as polymorphisms.

Someone's gotta step up and do a big ole' MK test between humans and chimps. I'm not talking Bustamante et al, only polymorphism in humans, but something that incorporates chimp polymorphism.

where the fuck is 'chimpdude' when you need him....

when looking as such closely related species, how can you get by ignoring the intraspecific polymorphism? How many of the "fixed differences" in this paper are actually segregating as polymorphisms.

you're right, but would this affect the relative number of detected genes that have undergone selection in chimps v. humans?

that is, the authors seem to (wrongly) think they're getting a picture of all selected genes in both lineages. but their conclusion (more selected genes in chimps than humans) would hold if they're looking at the exact same percentage of selected genes in humans and chimps. do you think taking into account polymorphism data would alter the relative numbers of detected selected genes?