PT  - JOURNAL ARTICLE
AU  - John Lindo
AU  - Emilia Huerta-Sánchez
AU  - Shigeki Nakagome
AU  - Morten Rasmussen
AU  - Barbara Petzelt
AU  - Joycellyn Mitchell
AU  - Jerome S Cybulski
AU  - Eske Willerslev
AU  - Michael DeGiorgio
AU  - Ripan S Malhi
TI  - Demographic and immune-based selection shifts before and after European contact inferred from 50 ancient and modern exomes from the Northwest Coast of North America
AID  - 10.1101/051078
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 051078
4099  - http://biorxiv.org/content/early/2016/04/29/051078.short
4100  - http://biorxiv.org/content/early/2016/04/29/051078.full
AB  - The susceptibility of Native Americans to infectious disease has been postulated as a major factor for their population decline after European contact. To investigate if a preexisting genetic component contributed to this phenomenon, we analyzed 50 exomes of both ancient and modern individuals from the Northwest Coast of North America, dating from before and after European contact. We confirmed the genetic continuity between the ancient and modern individuals and modeled the population collapse after European contact, inferring a 57% reduction in effective population size. We also identified signatures of positive selection on immune-related genes in the ancient but not the modern group. The strongest selection signal in the ancients came from the human leukocyte antigen (HLA) gene HLA-DQA1, with alleles that are close to fixation. The important immune function of HLA-DQA1 supports an ancient adaptation to the environments of the Americas. The modern individuals show a marked decrease in the frequency of the associated alleles (the most pronounced variant showing a 64% difference). This decrease is likely due to the environmental change associated with European colonization, which resulted in a shift of selection pressures, whereby negative selection may have acted on the same gene after contact. Furthermore, the selection pressure shift could correlate to the European-borne epidemics of the 1800s, suffered in the Northwest Coast region. This is among the first studies to examine a single population through time and exemplifies the power of such studies in uncovering nuanced demographic and adaptive histories.