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• W3120331510 abstract "Abstract Molecular sequences are shaped by selection, where the strength of selection relative to drift is determined by effective population size ( N e ). Populations with high N e are expected to undergo stronger purifying selection, and consequently to show a lower substitution rate for selected mutations relative to the substitution rate for neutral mutations ( ω ). However, computational models based on biophysics of protein stability have suggested that ω can also be independent of N e , a result proven under general conditions. Together, the response of ω to changes in N e depends on the specific mapping from sequence to fitness. Importantly, an increase in protein expression level has been found empirically to result in decrease of ω , an observation predicted by theoretical models assuming selection for protein stability. Here, we derive a theoretical approximation for the response of ω to changes in N e and expression level, under an explicit genotype-phenotype-fitness map. The method is generally valid for additive traits and log-concave fitness functions. We applied these results to protein undergoing selection for their conformational stability and corroborate out findings with simulations under more complex models. We predict a weak response of ω to changes in either N e or expression level, which are interchangeable. Based on empirical data, we propose that fitness based on the conformational stability may not be a sufficient mechanism to explain the empirically observed variation in ω across species. Other aspects of protein biophysics might be explored, such as protein-protein interactions, which can lead to a stronger response of ω to changes in N e ." @default.
• W3120331510 created "2021-01-18" @default.
• W3120331510 creator A5045305618 @default.
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• W3120331510 date "2021-01-13" @default.
• W3120331510 modified "2023-10-04" @default.
• W3120331510 title "A theoretical approach for quantifying the impact of changes in effective population size and expression level on the rate of coding sequence evolution" @default.
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• W3120331510 doi "https://doi.org/10.1101/2021.01.13.426437" @default.
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