A conjoint analysis of renal structure and omics characteristics reveal new insight to yak high-altitude hypoxia adaptation

Yuan Ding; Fangfang Zhao; Jiang Hu; Zhidong Zhao; Bingang Shi; Shaobin Li

doi:10.1016/j.ygeno.2024.110857

A conjoint analysis of renal structure and omics characteristics reveal new insight to yak high-altitude hypoxia adaptation

Genomics. 2024 May 8;116(4):110857. doi: 10.1016/j.ygeno.2024.110857. Online ahead of print.

Authors

Yuan Ding¹, Fangfang Zhao², Jiang Hu¹, Zhidong Zhao¹, Bingang Shi¹, Shaobin Li³

Affiliations

¹ Gansu Key Laboratory of Herbivorous Animal Biotechnology, Faculty of Animal Science and Technology, Gansu Agricultural University, Lanzhou 730070, China.
² Gansu Key Laboratory of Herbivorous Animal Biotechnology, Faculty of Animal Science and Technology, Gansu Agricultural University, Lanzhou 730070, China. Electronic address: zhaofangfang@gsau.edu.cn.
³ Gansu Key Laboratory of Herbivorous Animal Biotechnology, Faculty of Animal Science and Technology, Gansu Agricultural University, Lanzhou 730070, China. Electronic address: lisb@gsau.edu.cn.

PMID: 38729453
DOI: 10.1016/j.ygeno.2024.110857

Abstract

Background: Yaks have unique adaptive mechanisms to the hypoxic environment, in which the kidney plays an important role. The aim of this study was to explore the histological changes of yak kidney at different altitudes and the metabolites and genes associated with adaptation to the hypoxic environment.

Methods: We analyzed the tissue structure and transcriptomic metabolomic data of yak kidney tissue at two altitudes, 2600 and 4400 m. We compared and identified the morphological adaptations of the kidney and the metabolites and genes associated with hypoxia adaptation in yaks. Changes in renal morphological adaptations, differential metabolites and genes were compared and identified, combining the two in a joint analysis.

Results: High-altitude yak kidneys showed significant adaptive changes: increased mitochondria, increased glomerular thylakoid area, and decreased localized ribosomes. Transcriptomics and metabolomics identified 69 DAMs (Differential metabolites) and 594 DEGs (differential genes). Functional enrichment analysis showed that the DAMs were associated with protein digestion and absorption, ABC transporter, and MTOR signaling pathway; the DEGs were significantly enriched in Cholesterol metabolism and P53 signaling pathway. The joint analysis indicated that metabolites such as lysine and arginine, as well as key genes such as ABCB5 and COL1A2, were particularly affected under hypoxic conditions, whereas changes in mitochondria in the tissue structure may be related to the expression of MFN1 and OPA1, and changes in glomerular thylakoid membranes are related to VEGFA and TGFB3.

Conclusion: The kidney regulates metabolites and gene expression related to hormone synthesis, protein metabolism, and angiogenesis by adjusting the mitochondrial and glomerular thylakoid membrane structure to support the survival of yaks in high-altitude environments.

Keywords: Kidney; Metabolomics; Plateau hypoxia adaptation; Transcriptomics; Ultrastructure; Yak.