I have been away over the weekend visiting my parents with my wife and son, and have just got back to this discussion today. I see that @cwhenderson has made some comments designed as a summary of where things are at. For my part I would briefly say this.
I came into this discussion with two questions in my mind:
- Does chapter three of Adam and the Genome make a convincing case that humans have never passed through a bottleneck of two?
- Is there a better case that can be made?
I came to both of these questions with an open mind. Regarding question (1) I had very serious concerns about Dennis’ chapter, which I expressed to him privately in an email in the spring, and then later made public. I did think that Dennis might be able to defend his chapter well when challenged and come up with missing references. So far, however, I have been disappointed with his defence of his chapter (thought grateful that he has made it), and I have growing certainty that even if his conclusion - that there never was such a bottleneck - is correct, it is correct for the wrong reasons. Regarding question (2) Dennis has cited some papers that were not alluded to in his book, which I still need to read. Given my disappointment in the other citations that Dennis has pointed me to in the past through his chapter and in this discussion, I am not optimistic that any of these will really support his case when examined closely. But I will read them in case they do prove his point. In addition, Steve Schaffner has given some evidence from allele frequency distributions that these make a case against a bottleneck of two. This is an intriguing argument, but I have questions that have not been fully dealt with regarding the role in the model of alleles that are derived from before the bottleneck, and also the effect of population structure. I also note that because Steve has presented this analysis that is not in the peer reviewed literature, it seems probable that he does not find what is already in the peer reviewed literature as convincing as Dennis does. I am also getting less optimistic that there is a strong case to be made against a bottleneck of two because I have not had any responses to my blog at Nature Eco Evo - which was aimed at research scientists and has been read many times - saying that I am clearly wrong and have missed a crucial piece of evidence that shows that a bottleneck of two is effectively disproven. I maintain an open mind on this wider issue however.
The reason why I stopped asking @glipsnort questions was because he was taking some time out over Thanksgiving, and he has not yet responded to the questions I posed just after he left the discussion.[quote=“DennisVenema, post:119, topic:37039”]
The only thing I would add is that some of the papers I have directed Richard to, such as the Alu paper and a few others, have not, as of yet, been responded to by Richard. These papers also test Richard’s hypothesis of a bottleneck to two, and reject it.
I will come on to those papers in due course, Dennis, as we have not yet completed our discussion of Zhao et al 2000, which is the first one of the batch of papers that you directed me to that I have addressed. As we have discussed, the parts of this paper that you highlighted did not test a hypothesis of a bottleneck of two and do not support your certainty against this hypotheses. I think you have agreed with that critique and we are now in the midst of a discussion as to whether or not the final coalescent analysis of the paper is persuasive evidence against a population bottleneck of two.
I have just had a read through the comments that you made about this since I have been away for the weekend. I am glad to see that you have backed away from your claim that 75 variants could not make it through a bottleneck of two, and that you are now talking about how they are arranged in haplotypes over the 10Kb region. That is much more appropriate and to the point. However, you present no analysis of the haplotype structure of the region we are discussing, nor do the authors Zhao et al write about this in any detail. You are quite out on a limb here, making claims about the data that the authors do not make.
Please could you present some analysis of their data and show that there are not four major haplotypes for the higher frequency variants that could have come through a bottleneck? As you know, linkage disequilibrium in the human genome means that very few of the haplotypes that are possible from existing SNVs are present in human populations.
Please note that I have already commented on your use to the Tenesa et al paper in my Nature Eco Evo blog, and I am looking forward to your response to my critique.
I would also note, Dennis, that as well as the outstanding task you have given me of reading though four more papers (which I plan to fulfil), I have also suggested a task for you that I believe remains outstanding:[quote=“RichardBuggs, post:108, topic:37039”]
to explain in your own words (without help from Steve) what Steve was modelling, and how it shows that a bottleneck of two is unlikely to have happened.
I am sure that many of the readers following this discussion would welcome such a summary.