Transcriptome Analysis of Circulating PBMCs to Understand Mechanism of High Altitude Adaptation in Native Cattle of Ladakh Region

Abstract

Ladakhi cattle is native population of Leh and Ladakh region and constantly exposed to hypobaric hypoxia over many generations. In present study, transcriptome signatures of cattle from Ladakh region (~5500 m) and Sahiwal cattle from tropical regions were evaluated using Agilent 44 K microarray chip. The top up-regulated genes in Ladakhi cows were INHBC, ITPRI, HECA, ABI3, GPR171, and HIF-1α involved in hypoxia and stress response. In Sahiwal cows, the top up-regulated genes eEF1A1, GRO1, CXCL2, DEFB3 and BOLA-DQA3 were associated with immune function and inflammatory response indicating their strong immune potential to combat the pathogens prevalent in the tropical conditions. The molecular pathways highly impacted were MAPK signaling, ETC, apoptosis, TLR signaling and NF- kB signaling pathway indicating signatures of adaptive evolution of these two cattle types in response to diverse environments. Further, qPCR analysis revealed increased expression of DEGs such as HIF-1, EPAS-1, VEGFA, NOS2, and GLUT-1/SLC2A1 in cattle types from high altitude suggesting their pivotal role in association with high altitude adaptation. Based on data generated, native cattle of Ladakh region was found to be genetically distinct from native cattle adapted to the tropical region of India.

Selection signatures for high‐altitude adaptation in ruminants

“…They did not find associations between variants of these candidate genes and the susceptibility to HAPH, but a follow‐up microarray analysis did reveal biologically relevant pathways involved in HAPH susceptibility by expression profiling of peripheral blood mononuclear cells (Newman et al ). A further transcriptome study of peripheral blood mononuclear cells of native Indian cattle revealed greater expression of the HIF‐1 , EPAS1 , VEGFA , NOS2 , and GLUT1/SLC2A1 genes in cattle from high altitude compared with low‐altitude individuals (Verma et al ). Other comparative transcriptome studies between cattle and yak revealed that, among several organs, gene expression patterns of the heart showed the greatest differentiation between the two species (Wang et al ) and that differentially expressed genes in lung and gluteus tissue are involved in red blood cell development and the inhibition of blood coagulation (Xin et al ).…”

Genomic divergence reveals unique populations among Indian Yaks

“…The EPAS1/HIF-2α which is a transcription factor that belong to hypoxia-inducible factor signaling pathway was found to be involved high altitude adaptation in through its role in response to hypoxia, erythropoiesis, iron homeostasis, pulmonary hypertension 1,11,[14][15][16] . ITPR1 gene is target of HIF-2α and is involved in high altitude adaptation mechanisms 12 . HIF-1α regulates the oxygen homeostasis in cells and also regulates glycolysis 17,18 .…”

“…NOS2 gene is expressed during the high altitude hypoxia and may aid in improved pulmonary capacity in high altitude 19 . GLUT1 like glucose transporters are responsible for anaerobic metabolism 12 . The SNPs identified in the candidate genes for high altitude adaptation need to be explored further in large population for its role in the adaptation process.…”

“…SNPs in the coding region were further grouped into missense, nonsense and silent SNPs. For gene wise annotation, the candidate genes for high altitude adaptation 11,12,32,33 were collected. The genomic location of the candidate genes were drawn from the NCBI database and the SNPs present in that region were captured from the annotated VCF file using VCFtools 34 .…”

“…for high altitude adaptation were selected from studies in cattle and yak 11,12 and SNPs were annotated in the genes (Supplementary Material 1).…”