Year: 2025
Type: dissertation
Abstract: Hydrogen sulfide (H2S) plays a crucial role in various physiological processes and has been implicated in modulating aging through its impacts on oxidative stress and cellular health. This thesis investigates the evolutionary dynamics of the cystathionine-β-synthase (CBS), the cystathionine-ƴ-lyase (CSE), and the 3-mercaptopyruvate sulfurtransferase (3-MST) genes, involved in endogenous H₂S production. I investigated CBS, CSE, and 3-MST in long-lived mammals, focusing on the naked mole-rat (Heterocephalus glaber). I hypothesized that these genes would exhibit signs of positive selection linked to extended lifespan. Codon-based evolutionary models results of 114 mammalian species revealed a relaxation of purifying selection instead of positive selection in CSE, but not CBS and 3-MST, in long-lived mammals. In the naked mole-rat, CSE exhibited clear signs of positive selection, particularly in residues with potential functional impact. These mutations possibly improve CSE catalytic efficiency and potentially H2S production, supporting the naked mole-rat's unique adaptations to its subterranean habitat and contributing to its remarkable lifespan.
Source: TSpace (University of Toronto)
Author: Ren, Junlin
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7133106381