The Non-synonymous/Synonymous substitution rate (Ka/Ks) ratio is a commonly used metric to estimate the selection pressure and evolutionary rate of proteins in comparative genomics, which plays critical roles in molecular evolution in both biology and medicine. A fundamental assumption of Ka/Ks is that synonymous mutations are evolutionarily neutral and not subject to natural selection as they do not alter protein sequences and function. Recently, however, a number of studies have demonstrated that synonymous mutations are non-neutral and functional through a number of mechanisms, such as altering miRNA regulation. This further implies that synonymous mutations also participate in the process of natural selection and thus Ka/Ks should be redefined as well. For this purpose, here we propose an improved Ka/Ks ratio, iKa/Ks, which considers the neutral mutation rate by taking the altered status of miRNA regulation of the synonymous mutations into consideration, and thereby incorporate the impact of synonymous mutations on miRNA regulation.
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Statistics
22106 human-mouse orthologous genes.
Contact Us
Dr Qinghua Cui, 38 Xueyuan Rd, Department of Biomedical Informatics, Peking University Health Science Center, Beijing 100191, China
Email: cuiqinghua@bjmu.edu.cn
Citing FDS
Ye J, Cui C, Fan R and Cui Q. Estimating the selection pressure and evolutionary rate of proteins on the non-neutral hypothesis of synonymous mutations.
Cui Lab, Department of Biomedical Informatics, School of Basic Medical Sciences, Peking University.