Evolution of high-molecular-mass hyaluronic acid is associated with subterranean lifestyle

Yang Zhao, Zhizhong Zheng, Zhihui Zhang, Yandong Xu, Eric Hillpot, Yifei S. Lin, Frances T. Zakusilo, J. Yuyang Lu, Julia Ablaeva, Seyed Ali Biashad, Richard A. Miller, Eviatar Nevo, Andrei Seluanov () and Vera Gorbunova ()
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Yang Zhao: University of Rochester
Zhizhong Zheng: University of Rochester
Zhihui Zhang: University of Rochester
Yandong Xu: Zhejiang University School of Medicine
Eric Hillpot: University of Rochester
Yifei S. Lin: University of Rochester
Frances T. Zakusilo: University of Rochester
J. Yuyang Lu: University of Rochester
Julia Ablaeva: University of Rochester
Seyed Ali Biashad: University of Rochester
Richard A. Miller: University of Michigan Medical School
Eviatar Nevo: University of Haifa
Andrei Seluanov: University of Rochester
Vera Gorbunova: University of Rochester

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: Abstract Hyaluronic acid is a major component of extracellular matrix which plays an important role in development, cellular response to injury and inflammation, cell migration, and cancer. The naked mole-rat (Heterocephalus glaber) contains abundant high-molecular-mass hyaluronic acid in its tissues, which contributes to this species’ cancer resistance and possibly to its longevity. Here we report that abundant high-molecular-mass hyaluronic acid is found in a wide range of subterranean mammalian species, but not in phylogenetically related aboveground species. These subterranean mammalian species accumulate abundant high-molecular-mass hyaluronic acid by regulating the expression of genes involved in hyaluronic acid degradation and synthesis and contain unique mutations in these genes. The abundant high-molecular-mass hyaluronic acid may benefit the adaptation to subterranean environment by increasing skin elasticity and protecting from oxidative stress due to hypoxic conditions. Our work suggests that high-molecular-mass hyaluronic acid has evolved with subterranean lifestyle.

Date: 2023
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DOI: 10.1038/s41467-023-43623-2

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