Genetic signatures of high-altitude adaptation and geographic distribution in Tibetan sheep

Abstract

Most sheep breeding programs designed for the tropics and sub-tropics have to take into account the impacts of environmental adaptive traits. However, the genetic mechanism regulating the multiple biological processes driving adaptive responses remains unclear. In this study, we applied a selective sweep analysis by combing 1% top values of Fst and ZHp on both altitude and geographic subpopulations (APS) in 636 indigenous Tibetan sheep breeds. Results show that 37 genes were identified within overlapped genomic regions regarding Fst significantly associated with APS. Out of the 37 genes, we found that 8, 3 and 6 genes at chromosomes (chr.) 13, 23 and 27, respectively, were identified in the genomic regions with 1% top values of ZHp. We further analyzed the INDEL variation of 6 genes at chr.27 (X chromosome) in APS together with corresponding orthologs of 6 genes in Capra, Pantholops, and Bos Taurus. We found that an INDEL was located within 5′UTR region of HAG1 gene. This INDEL of HAG1 was strongly associated with the variation of APS, which was further confirmed by qPCR. Sheep breeds carrying “C-INDEL” of HAG1 have significantly greater body weight, shear amount, corpuscular hemoglobin and globulin levels, but lower body height, than those carrying “CA-INDEL” of HAG1. We concluded that “C-INDEL” variation of HAG1 gene confers better hypoxia tolerance in the highlands of Tibetan and explains well geographic distributions in this population. These results contribute to our understanding of adaptive responses to altitude and geographic adaptation in Tibetan sheep populations and will help to guide future conservation programs for Tibetan sheep native to Qinghai-Tibetan Plateau.

Comparative and population genomics analyses of eared pheasants inhabiting highly varying altitudes

“…Interestingly, these unique genes and genes with loss-of-function mutations (pseudogenization or missing) are mainly involved in and affect, respectively, pathways related to four functional categories: cardiovascular, neuronal, energy metabolic and immune functions. One way of alteration of these functions due to the presence or loss of function of the genes in WT might be related to its adaptation to high altitude, as have been reported for other high-altitude adapted species and populations of humans and animals 4,7,11,15,18,19,22,23,31 . The opposite way of alteration of these functions due to the loss of function and presence of the genes in BR might be related to its adaptation to low altitude.…”

“…The major challenge faced by these populations of humans and animals in highland environments is the low oxygen pressureinduced stress on their physiological systems [17][18][19] . The long-term adaptation to the stress has resulted in genetic changes in these human 1-3,14,17,20-27 and animal [4][5][6][7][10][11][12][13][14][15][16]19,[28][29][30][31] populations as a result of long-term adaptation to the low oxygen pressure environments. Adaptive mutations of many genes of humans 2, 14,17,18,26,32,33 and animals 16,19,30,31,33,34 have been linked to highland environments.…”

Genetic structure and characteristics of Tibetan chickens

“…This suggests that TBC sub-groups responded to similar selection pressures in an independent but possible functionally similar fashion. Moreover, we caution that such robust population structure might not be a unique characteristic for TBC, but could be a more wide-spread phenomenon in other highland organisms ( Ai et al, 2014 ; Janeš et al, 2019 ; Liu et al, 2020b ). Future genetic utilization or studies on them should be cautious of the implications the population substructures would bring, so that thoughtful experimental design must be applied.…”

Genomic adaptation of Ethiopian indigenous cattle to high altitude

“…This gene was also reported to protect cells from oxidative stress caused by hypoxia (Hansel et al, 2005) as well as from cold and heat stress (Lim et al, 2012). RXFP2 was reported to control horn type, development, and morphology (Pan et al, 2018; Ahbara Frontiers in Genetics frontiersin.org 07 Liu et al, 2020) and linked to high-altitude adaptation to hypoxia in sheep (Guo et al, 2021).…”