Genome-wide analysis reveals adaptation to high altitudes in Tibetan sheep

Abstract

Tibetan sheep have lived on the Tibetan Plateau for thousands of years; however, the process and consequences of adaptation to this extreme environment have not been elucidated for important livestock such as sheep. Here, seven sheep breeds, representing both highland and lowland breeds from different areas of China, were genotyped for a genome-wide collection of single-nucleotide polymorphisms (SNPs). The FST and XP-EHH approaches were used to identify regions harbouring local positive selection between these highland and lowland breeds, and 236 genes were identified. We detected selection events spanning genes involved in angiogenesis, energy production and erythropoiesis. In particular, several candidate genes were associated with high-altitude hypoxia, including EPAS1, CRYAA, LONP1, NF1, DPP4, SOD1, PPARG and SOCS2. EPAS1 plays a crucial role in hypoxia adaption; therefore, we investigated the exon sequences of EPAS1 and identified 12 mutations. Analysis of the relationship between blood-related phenotypes and EPAS1 genotypes in additional highland sheep revealed that a homozygous mutation at a relatively conserved site in the EPAS1 3′ untranslated region was associated with increased mean corpuscular haemoglobin concentration and mean corpuscular volume. Taken together, our results provide evidence of the genetic diversity of highland sheep and indicate potential high-altitude hypoxia adaptation mechanisms, including the role of EPAS1 in adaptation.

Whole-genome sequencing of eight goat populations for the detection of selection signatures underlying production and adaptive traits

“…CDK2 is a selected gene in the Tibetan mastiff52, and is involved in hypoxia-induced apoptosis in cardiomyocytes53. SOCS2 is implicated as a selective gene in Tibetan sheep54. NOXA1 is the activator of NOX1, which is associated with HIF-1 response under intermittent hypoxia conditions55.…”

Selection signatures for high‐altitude adaptation in ruminants

“…For example, novel potential selection targets for altitude adaptation were found in different high‐altitude sheep populations, e.g. the SOCS2 (suppressor of cytokine signaling 2) gene (Wei et al ; Yang et al ), mentioned above, and the FGF7 (keratinocyte growth factor 7) gene (Gorkhali et al ). Specific genetic variants of the SOCS2 gene were found in Tibetan sheep but in no other sheep breeds; in these Tibetan sheep, SOCS2 expression levels were significantly higher in liver than in other organs, suggesting a role in energy metabolism and thus highlighting the importance of glycolysis and volatile fatty acids (VFAs) in response to high altitude (Yang et al ).…”

“…A convergent adaptive signature identified across species, e.g. sheep (Wei et al 2016), goats (Song et al 2016) and humans and dogs (Wang et al 2014), is genetic variation at the EPAS1 gene (endothelial PAS domain-containing protein 1 or HIF2A), which is also a strong candidate gene for HAPH in cattle (Newman et al 2015). EPAS1 encodes the hypoxia-inducible transcription factor HIF-2a and regulates erythropoietin production, which influences haemoglobin levels (Percy et al 2008).…”

Novel and known signals of selection for fat deposition in domestic sheep breeds from Africa and Eurasia

“…The signature on OAR3:154.0-155.6 Mb (S2 Fig and Table 4), detected in the Laticauda and the Libyan Barbary breeds, had already been reported for the Barbaresca, Laticauda and Chios breeds [9]. Yuan et al [11], in a GWAS on seven indigenous Chinese sheep, by contrasting fat-tail versus thin-tail phenotypes, detected a signature in this region encompassing the MSRB3 , that has been identified as a candidate gene associated with adaptation [24]. In a study on world sheep breeds, MSRB3 was highlighted to have experienced high selection pressure [25].…”