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Is ADSL the locus of human genius?

God knows I would sleep more if it weren’t for bioRxiv. A new single author preprint debuts a new method, 3P-CLR, which extends XP-CLR, as a method to detect natural selection. The key is that it uses an explicit three-population tree to pick up selection events after the most recent, and second most recent, divergence events. So in the tree of ((Eurasians , Africans)Archaic Humans), this method can pick up perturbations which suggest selection after the emergence of a coherent anatomically modern population, but before it differentiated into its gorgeous mosaic.

In any case, the most recent version of the preprint, Testing for ancient selection using cross-population allele frequency differentiation:

A powerful way to detect selection in a population is by modeling local allele frequency changes in a particular region of the genome under scenarios of selection and neutrality, and finding which model is most compatible with the data. Chen et al. (2010) developed a composite likelihood method called XP-CLR that uses an outgroup population to detect departures from neutrality which could be compatible with hard or soft sweeps, at linked sites near a beneficial allele. However, this method is most sensitive to recent selection and may miss selective events that happened a long time ago. To overcome this, we developed an extension of XP-CLR that jointly models the behavior of a selected allele in a three-population tree. Our method – called 3P-CLR – outperforms XP-CLR when testing for selection that occurred before two populations split from each other, and can distinguish between those events and events that occurred specifically in each of the populations after the split. We applied our new test to population genomic data from the 1000 Genomes Project, to search for selective sweeps that occurred before the split of Africans and Eurasians, but after their split from Neanderthals, and that could have presumably led to the fixation of modern-human-specific phenotypes. We also searched for sweep events that occurred in East Asians, Europeans and the ancestors of both populations, after their split from Africans.

The software will be posted on the author’s github when the manuscript is accepted somewhere.

A minor note is that the data set used was from the 1000 Genomes. The Sub-Saharan Africans then are not from the hunter-gatherer populations, the Khoisan and the Pygmy, who seem to have the largest reservoir of genetic variation. The figure above is from a major signal of selection which is specific to modern humans, but excluded from the Neandertal populations. That is, fixed in us for a derived mutation, fixed in our cousins for the ancestral type (ancestral as judged by reference to the chimpanzee outgroup). My main curiosity is to push the three-population model so that it is ((Khoisan, non-Khoisan)Archaic Humans). I know from ASHG that there are now a fair amount of good quality whole genomes from African hunter-gatherers, so no doubt people are looking for these signatures.

The holy grail here for some geneticists (e.g., Svante Paabo) is to find that gene or genes which changed in us to make us sui generis. I no longer believe that this will ever be found. Assuming tens of millions of polymorphisms floating around in the genome no doubt candidate genes will emerge, just like FOXP2 did all those years ago. But I no longer believe that there is a necessary or sufficient genetic variant for our humanity. It’s a quantitative trait, and many of the hominin lineages were actually stumbling in the same direction.

On a more optimistic note, those of us who work on non-human genomes will also have data sets to rival those who are savants of humanics in the near future, so these methods are generally useful.

Citation: Testing for ancient selection using cross-population allele frequency differentiation, Fernando Racimo, bioRxiv doi:

• Category: Science • Tags: 3P-CLR, Human Evolution, Selection 
Razib Khan
About Razib Khan

"I have degrees in biology and biochemistry, a passion for genetics, history, and philosophy, and shrimp is my favorite food. If you want to know more, see the links at"