Molecular evolution of the p53 network in reptiles

Parsai, Shikha
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The p53 molecular network is a master regulator of how cells respond to DNA-damaging stresses. Its primary function is to respond to DNA-damage by several options: apoptosis, cellular senescence, and temporary arrest of cellular growth for DNA repair. The p53 network's tight regulation of cellular fate after damage has obvious beneficial effects of preventing tumorigenesis, and possible costly effects later in life such as the accumulation of damaged cells and other aging phenotypes. Because many reptile species have evolved unique organismal stress responses, we tested the related hypothesis that the evolutionary dynamics of, and mode of selection on, genes within the p53 network differs between reptiles and mammals, and that these differences may underlie the evolution of stress response diversity. We analyzed 32 genes of the p53 network in both reptiles and mammals to compare the rates of evolutionary change and the modes of selection, (i.e., positive or purifying). We utilized transcriptomes of seventeen reptile species in order to determine protein-coding nucleotide sequences for these genes in the p53 network and performed molecular evolutionary selection analyses. We found that several genes involved in apoptosis, DNA repair and damage prevention, and inhibiting mTOR, which is an aging pathway, are undergoing different levels of selection in reptiles when compared to mammals. We discuss these findings in the context of unique adaptations to stressors found in reptiles and propose future functional research.