Evolutionary genomic footprints for highaltitude adaptation in native cattle (Bos indicus), yak (Bos grunniens) and their crossspecies hybrids (Bos indicus x Bos grunniens) in Trans-Himalaya

Abstract

Human and animals of high altitudes are well adapted to hypothermic and hypoxic conditions, however, genomic evolution for the adaptation seems to be taken place, differently. Native cattle (Bos indicus), yak (Bos grunniens) and their cross-hybrids (Bos indicus × Bos grunniens) in Trans Himalayan region (3000 meter and above from msl) of India were studied to dissect the differences of molecular evolution. DNA samples of 12 each of cattle and yak and six of cross-hybrids were sequenced using double digestion restriction-site associated DNA (ddRAD) technique and further annotated and compared using a pipeline of online bioinformatic tools to identify different species-specific selection sweeps as well and commonly selected genes in these native stocks. A total of 4985 (921 genes) and 1168 (342 genes) and 1945 (423 genes) selection sweeps were identified in native cattle of Ladak (Ladakhi cattle), Ladakhi yak and their hybrids, respectively using integrated Haplotype Score (iHS) method. However, to tackle the high-altitude stressors selection sweeps responded to different sets of genes in cattle and yak. Ladakhi cattle primarily responded by PML, KCNMA1 and PRKCB genes; whereas Ladakhi yak responded by HIF1A, RYR2 and NOS2 genes. Major co-selected genes pertaining to adaptive processes in three bovines were identified using the XP-EHH based pairwise comparison. PTPRM, STARD13, CHRNA7, LOXL2 and AMOTL2 were having major role in adaptive hypoxia regulation; PKP2, RYR2 and GJA1 in adaptive cardiac regulation; PTPRK, HUS1, SOS1, EGFR and ADAMTS2 in cutaneous adaptation, and AKT3, IRS2, PTHIGFBP5, PPARA and EGR genes in adaptive energy metabolism commonly in all three high-altitude bovines. The study dissects the genomic regions of three native bovines under selection to high altitude and identify common as well as diverging genomic regions, evolved in view of highaltitude adaptation in native cattle, yak and their hybrids in Trans-Himalaya.