Patterns of selection on Neanderthal alleles in modern humans

SMBE 2013 abstract:

A Genome-Wide Map of Neandertal Ancestry Documents the Effects of Selection on Introgressing Neandertal Material

Sriram Sankararaman1,2, Swapan Mallick1,2, Svante Pääbo3, Nick Patterson2, David Reich1,2 1Harvard Medical School; 2Broad Institute; 3Max Planck Institute for Evolutionary Anthropology

Analysis of archaic genomes has documented 1-4% gene flow from Neandertals into the ancestors of all non-Africans. As a first step to understanding the phenotypic impact of introgressed regions, we built a map of Neandertal ancestry in modern humans, using data from all populations in Phase 1 of the 1000 genomes project, combined with a high coverage (50×) Neandertal genome.

• We identified Neandertal alleles that are at higher frequency than expected under a model of neutral evolution, and identify dozens of genomic locations in Europeans and East Asians at which the Neandertal alleles are the targets of positive selection. Interestingly, there is evidence for more extensive positive selection in East Asian than in European populations.

• We discovered many more large genomic regions that are deficient in Neandertal ancestry than expected by chance. These regions are about 10 Mb on average and about half are shared between the European and East Asian populations. These observations are consistent with a model in which these regions harbor hybrid incompatibility loci where Neandertal variants that introgressed into modern humans were rapidly selected away.

• There is variation in the Neandertal ancestry across chromosomes, with chromosome X being a desert (a third of the average) that contains only a few oases of Neandertal ancestry. This further supports the hypothesis of genetic incompatibility between Neandertals and modern humans, as hybrid incompatibility loci are known to concentrate on chromosome X.

• By piecing together the segments of confidently inferred Neandertal ancestry, we create a tiling path covering about 40% of the genome that allows us to infer Neandertal ancestry even at repetitive elements. We combine this with direct Neandertal sequence data to obtain a more complete Neandertal reference genome sequence.