摘要：Ba c k g r o u n d: Arsenic in drinking water causes severe health effects. Indigenous people in the South American Andes have likely lived with arsenic-contaminated drinking water for thousands of years. Inhabitants of San Antonio de los Cobres (SAC) in the Argentinean highlands generally carry an AS3MT (the major arsenic-metabolizing gene) haplo type associated with reduced health risks due to rapid arsenic excretion and lower urinary fraction of the monomethylated metabolite.oB j e c t i v e s: We hypothesized an adaptation to high-arsenic living conditions via a possible positive selection for protective AS3MT variants and compared AS3MT haplo type frequencies among differ-ent indigenous groups.Me t h o d s: Indigenous groups we evaluated were a) inhabitants of SAC and villages near Salta in northern Argentina (n = 346), b) three Native American popu la tions from the Human Genome Diversity Project (HGDP; n = 25), and c) five Peruvian popu la tions (n = 97). The last two groups have presumably lower historical exposure to arsenic.re s u l t s: We found a significantly higher frequency of the protective AS3MT haplo type in the SAC popu la tion (68.7%) compared with the HGDP (14.3%, p < 0.001, Fisher exact test) and Peruvian (50.5%, p < 0.001) popu la tions. Genome-wide micro satellite (n = 671) analy sis showed no detect-able level of popu la tion structure between SAC and Peruvian popu la tions (measure of popu la tion differentiation FST= 0.006) and low levels of structure between SAC and HGDP popu la tions (FST< 0.055 for all pairs of popu la tions compared).co n c l u s i o n s: Because popu la tion stratification seems unlikely to explain the differences in AS3MT haplo type frequencies, our data raise the possibility that, during a few thousand years, natural selec-tion for tolerance to the environmental stressor arsenic may have increased the frequency of protec-tive variants of AS3MT. Further studies are needed to investigate this hypothesis
