Person:

Sankararaman, Sriram

Strong signatures of positive selection at newly arising genetic variants are well-documented in humans, but this form of selection may not be widespread in recent human evolution. Because many human traits are highly polygenic and partly determined by common, ancient genetic variation, an alternative model for rapid genetic adaptation has been proposed: weak selection acting on many pre-existing (standing) genetic variants, or polygenic adaptation. By studying height, a classic polygenic trait, we demonstrate the first human signature of widespread selection on standing variation. We show that frequencies of alleles associated with increased height, both at known loci and genome-wide, are systematically elevated in Northern Europeans compared with Southern Europeans ((p<4.3×10^{−4})). This pattern mirrors intra-European height differences and is not confounded by ancestry or other ascertainment biases. The systematic frequency differences are consistent with the presence of widespread weak selection (selection coefficients (~10^{−3}–10^{−5}) per allele) rather than genetic drift alone ((p<10^{−15})).

Comparisons of DNA sequences between Neandertals and present-day humans have shown that Neandertals share more genetic variants with non-Africans than with Africans. This could be due to interbreeding between Neandertals and modern humans when the two groups met subsequent to the emergence of modern humans outside Africa. However, it could also be due to population structure that antedates the origin of Neandertal ancestors in Africa. We measure the extent of linkage disequilibrium (LD) in the genomes of present-day Europeans and find that the last gene flow from Neandertals (or their relatives) into Europeans likely occurred 37,000–86,000 years before the present (BP), and most likely 47,000–65,000 years ago. This supports the recent interbreeding hypothesis and suggests that interbreeding may have occurred when modern humans carrying Upper Paleolithic technologies encountered Neandertals as they expanded out of Africa.