Evolutionary Genetics of Hypoxia and Cold Tolerance in Mammals

  • Kangli Zhu
  • Deyan Ge
  • Zhixin Wen
  • Lin Xia
  • Qisen Yang
Original Article


Low oxygen and fluctuant ambient temperature pose serious challenges to mammalian survival. Physiological adaptations in mammals to hypoxia and low temperatures have been intensively investigated, yet their underlying molecular mechanisms need further exploration. Independent invasions of high-altitude plateaus, subterranean burrows and marine environments by different mammals provide opportunities to conduct such analyses. Here, we focused on six genes in the hypoxia inducible factor (HIF) pathway and two non-shivering thermogenesis (NST)-related genes [PPAR co-activator 1 (PGC-1) and uncoupling protein 1 (UCP1)] in representative species of pikas and other mammals to understand whether these loci were targeted by natural selection during independent invasions to conditions characterized by hypoxia and temperature fluctuations by high-altitude, subterranean and marine mammals. Our analyses revealed pervasive positive selection signals in the HIF pathway genes of mammals occupying high-altitude, subterranean and aquatic ecosystems; however, the mechanisms underlying their independent adaptations to hypoxic environments varied by taxa, since different genes were positively selected in each taxon and expression levels of individual genes varied among species. Additionally, parallel amino acid substitutions were also detected in hypoxia-tolerant mammals, indicating that convergent evolution may play a role in their independent adaptations to hypoxic environments. However, divergent evolutionary histories of NST-related genes were noted, since significant evidence of positive selection was observed in PGC-1 and UCP1 in high-altitude species and subterranean rodents; however, UCP1 may have already lost its function in diving cetaceans, which may be related to the thick blubber layer of adipose and connective tissue in these mammals.


Hypoxia Low temperature Adaptive evolution HIF pathway NST Differential expression 



This work was supported by Key Laboratory of Zoological Systematics and Evolution of the Chinese Academy of Sciences (No. Y229YX5105) and National Special Fund on Basic Research of Science and Technology of China (No. 2014FY110100). The authors wish to thank the members of our lab for collecting samples for so many years.

Supplementary material

239_2018_9870_MOESM1_ESM.docx (2 mb)
Supplementary material 1 (DOCX 2020 KB)


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Kangli Zhu
    • 1
  • Deyan Ge
    • 1
  • Zhixin Wen
    • 1
  • Lin Xia
    • 1
  • Qisen Yang
    • 1
  1. 1.Key Laboratory of Zoological Systematics and Evolution, Institute of ZoologyChinese Academy of SciencesBeijingChina

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