Alternative telomere maintenance mechanism in Alligator sinensis provides insights into aging evolution

Yu-Zun Guo; Yi Zhang; Qing Wang; Jun Yu; Qiu-Hong Wan; Jun Huang; Sheng-Guo Fang

doi:10.1016/j.isci.2022.105850

Alternative telomere maintenance mechanism in Alligator sinensis provides insights into aging evolution

iScience. 2022 Dec 24;26(1):105850. doi: 10.1016/j.isci.2022.105850. eCollection 2023 Jan 20.

Authors

Yu-Zun Guo¹, Yi Zhang¹, Qing Wang², Jun Yu¹, Qiu-Hong Wan¹, Jun Huang^{3

4}, Sheng-Guo Fang¹

Affiliations

¹ MOE Key Laboratory of Biosystems Homeostasis & Protection, State Conservation Centre for Gene Resources of Endangered Wildlife, College of Life Sciences, Zhejiang University, Hangzhou 310058, PR China.
² College of Life Science, University of Chinese Academy of Science, Beijing 100049, China.
³ Zhejiang Provincial Key Lab of Geriatrics and Geriatrics Institute of Zhejiang Province, Department of Geriatrics, Zhejiang Hospital, Hangzhou, Zhejiang 310030, China.
⁴ Zhejiang Provincial Key Laboratory of Cancer Molecular Cell Biology, Life Sciences Institute Zhejiang University, Hangzhou, Zhejiang 310058, China.

Abstract

Lifespan is a life-history trait that undergoes natural selection. Telomeres are hallmarks of aging, and shortening rate predicts species lifespan, making telomere maintenance mechanisms throughout different lifespans a worthy topic for study. Alligators are suitable for the exploration of anti-aging molecular mechanisms, because they exhibit low or even negligible mortality in adults and no significant telomere shortening. Telomerase reverse transcriptase (TERT) expression is absent in the adult Alligator sinensis, as in humans. Selection analyses on telomere maintenance genes indicated that ATM, FANCE, SAMHD1, HMBOX1, NAT10, and MAP3K4 experienced positive selection on A. sinensis. Repressed pleiotropic ATM kinase in A. sinensis suggests their fitness optimum shift. In ATM downstream, Alternative Lengthening of Telomeres (ALT)-related genes were clustered in a higher expression pattern in A. sinensis, which covers 10-15% of human cancers showing no telomerase activities. In summary, we demonstrated how telomere shortening, telomerase activities, and ALT contributed to anti-aging strategies.

Keywords: Evolutionary biology; Molecular biology; Zoology.