RT Journal Article SR Electronic T1 Evidence of a nonadaptive buildup of mutational load in human populations over the past 40,000 years JF bioRxiv FD Cold Spring Harbor Laboratory SP 307058 DO 10.1101/307058 A1 Stéphane Aris-Brosou YR 2018 UL http://biorxiv.org/content/early/2018/04/25/307058.abstract AB The role played by natural selection in shaping present-day human populations has received extensive scrutiny [1, 2, 3], especially in the context of local adaptations [4]. However, most studies to date assume, either explicitly or not, that populations have been in their current locations long enough to adapt to local conditions [5], and that population sizes were large enough to allow for the action of selection [6]. If these conditions were satisfied, not only should selection be effective at promoting local adaptations, but deleterious alleles should also be eliminated over time. To assess this prediction, the genomes of 2,062 individuals, including 1,179 ancient humans, were reanalyzed to reconstruct how frequencies of risk alleles and their homozygosity changed through space and time in Europe. While the overall deleterious homozygosity consistently decreased through space and time, risk alleles have shown a steady increase in frequency. Even the mutations that are predicted to be most deleterious fail to exhibit any significant decrease in frequency. These conclusions do not deny the existence of local adaptations, but highlight the limitations imposed by drift and range expansions on the strength of selection in purging the mutational load affecting human populations.