On Characterizing Adaptive Events Unique to Modern Humans Authors

1 Ever since the first draft of the human genome was completed in 2001 there has been 2 increased interest in identifying genetic changes that are uniquely human, which could account 3 for our distinct morphological and cognitive capabilities with respect to other apes. Recently, 4 draft sequences of two extinct hominin genomes, a Neanderthal and Denisovan, have been 5 released. These two genomes provide a much greater resolution to identify human-specific 6 genetic differences than the chimpanzee, our closest extant relative. The Neanderthal genome 7 paper presented a list of regions putatively targeted by positive selection around the time of the 8 human-Neanderthal split. We here seek to characterize the evolutionary history of these 9 candidate regions examining evidence for selective sweeps in modern human populations, as 10 well as for accelerated adaptive evolution across apes. Results indicate that 3 of the top 20 11 candidate regions show evidence of selection in at least one modern human population (p 12 <5x10). Additionally, 4 genes within the top 20 regions show accelerated amino acid 13 substitutions across multiple apes (p <0.01), suggesting importance across deeper evolutionary 14 time. These results highlight the importance of evaluating evolutionary processes across both 15 recent and ancient evolutionary timescales, and intriguingly suggest a list of candidate genes that 16 may have been uniquely important around the time of the human-Neanderthal split. 17 18