Abstract
Tibetan pigs have survived at high altitude for millennia and they have a suite of adaptive features to tolerate the hypoxic environment. However, the molecular mechanisms underlying the regulation of hypoxia-adaptive phenotypes have not been completely elucidated. In this study, we analyzed differentially expressed genes (DEGs), biological pathways and constructed co-expression regulation networks using whole-transcriptome microarrays from lung tissues of Tibetan and Duroc pigs both at high and low altitude. A total of 3,066 DEGs were identified and this list was over-represented for the ontology terms including metabolic process, catalytic activity, and KEGG pathway including metabolic pathway and PI3K-Akt signaling pathway. The regulatory (RIF) and phenotypic (PIF) impact factor analysis identified several known and several potentially novel regulators of hypoxia adaption, including: IKBKG, KLF6 and RBPJ (RIF1), SF3B1, EFEMP1, HOXB6 and ATF6 (RIF2). These findings provide new details of the regulatory architecture of hypoxia-adaptive genes and also insight into which genes may undergo epigenetic modification for further study in the high-altitude adaptation.
Highlights
The hypoxic environment at high altitude imposes extreme physiological challenges in mammals
Tibetan pigs were raised at Yunnan (Shangri-La Specialized Farmers Cooperatives, Tibetan Autonomous Prefecture of Diqing, 3,500 m) (Tibetan pigs at high altitude, mentioned as TH), and Duroc pigs were raised at Guangdong
These differentially expressed genes (DEGs) reflected the difference between breeds (Tibetan vs. Duroc) affected by the interaction that may be responsible for the adaptation of Tibetan pigs to high altitude (S1 and S4 Tables)
Summary
The hypoxic environment at high altitude imposes extreme physiological challenges in mammals. Classical response to hypoxia is characterized by systemic changes in cardiovascular, respiratory, and hematopoietic functions that impact convective oxygen transport. Failure of these systems to adapt leads to altitude illness or even death [1, 2]. Native high-altitude species have been selected through evolutionary processes to have heritable genetic adaptations [3] in morphological, anatomical, physiological [4], biochemical, and behavioral traits to survive under low oxygen tension [5,6,7].
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