Adaptation to Extreme Environments in an Admixed Human Population from the Atacama Desert

Abstract

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—PBSn1 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 PBSn1 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 PBSn1 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.

Postadmixture Selection on Chileans Targets Haplotype Involved in Pigmentation, Thermogenesis and Immune Defense against Pathogens

“…(2010) . We used an SNP array data set from a previous study ( Vicuna et al. 2019 ) consisting of 185 admixed subjects (121 males and 64 females) with mostly European and Native American ancestry from the Atacama Region of Northern Chile.…”

“…2019 ; Ko et al 2014 ). Further, a recent study found that PAS acting on Native American genetic variation may have aided a population with Native American and European ancestry from the Atacama Desert of Northern Chile to adapt to the pathophysiological effects of chronic exposure to high arsenic levels in water ( Vicuna et al. 2019 ).…”

“…The aim of this study was to evaluate whether Europeans provided adaptive genetic variation to admixed Chileans by acting through PAS following the Columbian exchange. We analyzed this selective force in a population from the Atacama Desert of Northern Chile ( Vicuna et al. 2019 ).…”

Integrated analysis of RNA binding proteins in human colorectal cancer

“…MAK16 encodes a ribosomal protein and plays an important role in ribosome biogenesis throughout the cell cycle [57]. In this study, it was found out that the mutations in MAK16 can induce the arrest of the cell cycle at G1 phase, during which the cell synthesizes mRNA and proteins as part of the preparation for cell division [58]. At present, there is still no role of MAK16 in the pathogenesis of tumors, which requires a further research to con rm.…”

Integrated analysis of RNA-binding proteins in human colorectal cancer

“…MAK16 encodes a ribosomal protein and plays an important role in ribosome biogenesis throughout the cell cycle [ 76 ]. In this study, it was found that mutations in MAK16 can induce cell cycle arrest at G1 phase, during which the cell synthesizes mRNA and proteins in preparation for cell division [ 77 ]. At present, there is still no study of the role of MAK16 in the pathogenesis of tumours, which requires further research to confirm.…”