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Detection of positive selection signatures in populations around the world is helping to uncover recent human evolutionary history as well as the genetic basis of diseases. Most human evolutionary genomic studies have been performed in European, African, and Asian populations. However, populations with Native American ancestry have been largely underrepresented. Here, we used a genome-wide local ancestry enrichment approach complemented with neutral simulations to identify postadmixture adaptations underwent by admixed Chileans through gene flow from Europeans into local Native Americans. The top significant hits (P  =   2.4×10−7) are variants in a region on chromosome 12 comprising multiple regulatory elements. This region includes rs12821256 , which regulates the expression of KITLG , a well-known gene involved in lighter hair and skin pigmentation in Europeans as well as in thermogenesis. Another variant from that region is associated with the long noncoding RNA RP11-13A1.1 , which has been specifically involved in the innate immune response against infectious pathogens. Our results suggest that these genes were relevant for adaptation in Chileans following the Columbian exchange. [ABSTRACT FROM AUTHOR]

Inorganic arsenic (As) is a toxic xenobiotic and carcinogen associated with severe health conditions. The urban population from the Atacama Desert in northern Chile was exposed to extremely high As levels (up to 600 µg/l) in drinking water between 1958 and 1971, leading to increased incidence of urinary bladder cancer (BC), skin cancer, kidney cancer, and coronary thrombosis decades later. Besides, the Andean Native-American ancestors of the Atacama population were previously exposed for millennia to elevated As levels in water (∼120 µg/l) for at least 5,000 years, suggesting adaptation to this selective pressure. Here, we performed two genome-wide selection tests—PBS n 1 and an ancestry-enrichment test—in an admixed population from Atacama, to identify adaptation signatures to As exposure acquired before and after admixture with Europeans, respectively. The top second variant selected by PBS n 1 was associated with LCE4A-C1orf68 , a gene that may be involved in the immune barrier of the epithelium during BC. We performed association tests between the top PBS n 1 hits and BC occurrence in our population. The strongest association (P  =   0.012) was achieved by the LCE4A-C1orf68 variant. The ancestry-enrichment test detected highly significant signals (P  =   1.3 × 10−9) mapping MAK16 , a gene with important roles in ribosome biogenesis during the G1 phase of the cell cycle. Our results contribute to a better understanding of the genetic factors involved in adaptation to the pathophysiological consequences of As exposure. [ABSTRACT FROM AUTHOR]