Novel alleles gained during the Beringian isolation period.

During the Last Glacial Maximum, a small band of Siberians entered the Beringian corridor, where they persisted, isolated from gene flow, for several thousand years before expansion into the Americas. The ecological features of the Beringian environment, coupled with an extended period of isolation at small population size, would have provided evolutionary opportunity for novel genetic variation to arise as both rare standing variants and new mutations were driven to high frequency through both neutral and directed processes. Here we perform a full genome investigation of Native American populations in the Thousand Genomes Project Phase 3 to identify unique high frequency alleles that can be dated to an origin in Beringia. Our analyses demonstrate that descendant populations of Native Americans harbor 20,424 such variants, which is on a scale comparable only to Africa and the Out of Africa bottleneck. This is consistent with simulations of a serial founder effects model. Tests for selection reveal that some of these Beringian variants were likely driven to high frequency by adaptive processes, and bioinformatic analyses suggest possible phenotypic pathways that were under selection during the Beringian Isolation period. Specifically, pathways related to cardiac processes and melanocyte function appear to be enriched for selected Beringian variants.