Signals of selection in the human genome: important new paper

I'll hopefully have more time to write about this tomorrow, but for now I'll simply suggest that you go and read the free full text PDF of this advance online manuscript in Genome Research.

This is the most important recent paper in the field of human evolutionary genetics - a thorough and careful analysis of the signatures of positive natural selection left in our genome by the last 10-40,000 years of adaptation, using a population sample that is far broader than those used in previous studies (53 populations rather than 4). I covered some of the approaches used in the paper in this post on the HGDP Selection Bowser, which is a graphical window into the same data used in this study.

There are plenty of interesting factual nuggets in there for anyone interested in recent human evolution (e.g. evidence for positive selection on type 2 diabetes susceptibility genes); but for those who follow human genetics online the most intriguing paragraph is this one:
Further exploration of the geographic patterns in these data and their implications is warranted, but from the point of view of identifying candidate loci for functional verification, the fact that putatively selected loci often conform to the geographic patterns characteristic of neutral loci is somewhat worrying. This suggests that distinguishing true cases of selection from the tails of the neutral distribution may be more difficult than sometimes assumed, and raises the possibility that many loci identified as being under selection in genome scans of this kind may be false positives. Reports of ubiquitous strong (s = 1-5%) positive selection in the human genome (Hawks et al. 2007) may be considerably overstated. [my emphasis]

Hawks et al. 2007 refers to this paper on the "recent acceleration" hypothesis of human evolution, championed by anthropologist blogger John Hawks and expanded on by Gregory Cochran and Henry Harpending in their recent book The 10000 Year Explosion. To my knowledge this is the first direct challenge to Hawks' hypothesis in the peer-reviewed literature; it will be interesting to see how this discussion develops.

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Hey Daniel,

Thanks for the kind comments on out paper (though I think it only qualifies as "the most important recent paper in the field of human evolutionary genetics" if you define recent as within the last couple days...)

I'll point out (as did John Hawks) that this paper is not an explicit test of the "acceleration hypothesis"--we express some skepticism about that hypothesis when discussing some of our results on geographical patterns of selection.

The reason the geographical results make me skeptical of the acceleration is that things like the lactase persistence allele (the canonical example of recent strong selection) show striking localized geographical patterns. We think we've put our finger on another such example (in Figure 6A, a non-synonymous variant in a Toll-like receptor), but overall, the regions of the genome that are extreme by haplotype-based methods do not show extreme geographical patterns.

By J Pickrell (not verified) on 24 Mar 2009 #permalink

Hi Joe,

Well, I phrased that "most important" statement very carefully, so readers could substitute their own values for "recent". :-) Still, don't undersell the importance of this paper: it's the juiciest morsel of human evolutionary genetic goodness to hit the journals for quite a while.

Thanks for the clarification on the acceleration hypothesis.

"Reports of ubiquitous strong (s = 1-5%) positive selection in the human genome (Hawks et al. 2007) may be considerably overstated. [my emphasis]

Hawks et al. 2007 refers to this paper on the "recent acceleration" hypothesis of human evolution, championed by anthropologist blogger John Hawks and expanded on by Gregory Cochran and Henry Harpending in their recent book The 10000 Year Explosion. To my knowledge this is the first direct challenge to Hawks' hypothesis in the peer-reviewed literature; it will be interesting to see how this discussion develops."

John Hawks has responded on his blog:

[snip copy-pasted text from Hawks' blog - DM]

http://johnhawks.net/weblog/topics/evolution/selection/acceleration/pic…