Mutation and Selection Induce Correlations between Selection Coefficients and Mutation Rates

Gitschlag, Bryan L, Cano, Alejandro V, Payne, Joshua L, McCandlish, David M, Stoltzfus, Arlin (October 2023) Mutation and Selection Induce Correlations between Selection Coefficients and Mutation Rates. The American Naturalist, 202 (4). pp. 534-557. ISSN 0003-0147

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Abstract

AbstractThe joint distribution of selection coefficients and mutation rates is a key determinant of the genetic architecture of molecular adaptation. Three different distributions are of immediate interest: (1) the "nominal" distribution of possible changes, prior to mutation or selection; (2) the "de novo" distribution of realized mutations; and (3) the "fixed" distribution of selectively established mutations. Here, we formally characterize the relationships between these joint distributions under the strong-selection/weak-mutation (SSWM) regime. The de novo distribution is enriched relative to the nominal distribution for the highest rate mutations, and the fixed distribution is further enriched for the most highly beneficial mutations. Whereas mutation rates and selection coefficients are often assumed to be uncorrelated, we show that even with no correlation in the nominal distribution, the resulting de novo and fixed distributions can have correlations with any combination of signs. Nonetheless, we suggest that natural systems with a finite number of beneficial mutations will frequently have the kind of nominal distribution that induces negative correlations in the fixed distribution. We apply our mathematical framework, along with population simulations, to explore joint distributions of selection coefficients and mutation rates from deep mutational scanning and cancer informatics. Finally, we consider the evolutionary implications of these joint distributions together with two additional joint distributions relevant to parallelism and the rate of adaptation.

Item Type:	Paper
Subjects:	bioinformatics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics evolution bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > mutations
CSHL Authors:	McCandlish, David Gitschlag, Bryan
Communities:	CSHL labs > McCandlish lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	October 2023
Date Deposited:	22 Nov 2023 13:30
Last Modified:	08 Jan 2024 20:57
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/41319

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