Genetic and Phenotypic Differentiation of an Andean Intermediate Altitude Population

Abstract

Highland populations living permanently under hypobaric hypoxia have been subject of extensive research because of the relevance of their physiological adaptations for the understanding of human health and disease. In this context, what is considered high altitude is a matter of interpretation and while the adaptive processes at high altitude (above 3000 m) are well documented, the effects of moderate altitude (below 3000 m) on the phenotype are less well established. In this study, we compare physiological and anthropometric characteristics as well as genetic variations in two Andean populations: the Calchaqu ıes (2300 m) and neighboring Collas (3500 m). We compare their phenotype and genotype to the sea-level Wich ı population. We measured physiological (heart rate, oxygen saturation, respiration rate, and lung function) as well as anthropometric traits (height, sitting height, weight, forearm, and tibia length). We conducted genome-wide genotyping on a subset of the sample (n = 74) and performed various scans for positive selection. At the phenotypic level (n = 179), increased lung capacity stood out in both Andean groups, whereas a growth reduction in distal limbs was only observed at high altitude. At the genome level, Calchaqu ıes revealed strong signals around PRKG1, suggesting that the nitric oxide pathway may be a target of selection. PRKG1 was highlighted by one of four selection tests among the top five genes using the population branch statistic. Selection tests results of Collas were reported previously. Overall, our study shows that some phenotypic and genetic differentiation occurs at intermediate altitude in response to moderate lifelong selection pressures.

Cardioprotection after acute exposure to simulated high altitude in rats. Role of nitric oxide

“…At a systemic level, the main effect of NO is to bring up the peripheral vasodilation [3,42], promoting a better supply of oxygen to the tissues [1]. In the pulmonary system, it functions to counterbalance the tendency to develop pulmonary hypertension [43]. In the present study we evaluated the cytosolic NOS system, finding a significant increase in the expression of both constitutive isoforms, eNOS and nNOS, in left ventricles of HH rats.…”

Selection Signatures Analysis Reveals Genes Associated with High-Altitude Adaptation in Tibetan Goats from Nagqu, Tibet

“…Among these genes, some genes were detected in other species. First was the ENPEP gene (Glutamyl aminopeptidase) ( di value = 7), which has biological functions associated with high-altitude adaptation and was also selected in the Tibetan sheep [ 23 ], Tibetan goat [ 7 ], and native Andeans [ 30 ]. Second was the MITF gene (melanocyte inducing transcription factor) ( di value = 8.36), which was selected for adaptation to high levels of ultraviolet radiation in Tibetan goats.…”

Positive selection of AS3MT to arsenic water in Andean populations

“…1). We used our previously published data [20,21] for 730,525 single nucleotide polymorphisms (SNPs) genotyped in 25 Collas (11 men, 14 women), 24 Calchaquíes (10 men, 14 women) and 24 Wichí (12 men, 12 women). In the Colla sample, 16 individuals were from San Antonio de los Cobres, where arsenic levels reach 214 µg/l [14]; 7 were from Tolar Grande with arsenic levels of 4 µg/l and one individual was from Olacapato, where arsenic levels are 12 µg/l.…”

“…In total, 726,090 SNPs passed a genotype call rate of >98% and were included in downstream analyses [20,21]. Two tests for positive selection were employed to analyze genome-wide signatures of arsenic adaptation.…”