Authors: Lee Altenberg
Publish Date: 2010/08/25
Volume: 73, Issue: 6, Pages: 1227-1270
Abstract
A model of mutation rate evolution for multiple loci under arbitrary selection is analyzed Results are obtained using techniques from Karlin Evolutionary Biology vol 14 pp 61–204 1982 that overcome the weak selection constraints needed for tractability in prior studies of multilocus event modelsA multivariate form of the reduction principle is found reduction results at individual loci combine topologically to produce a surface of mutation rate alterations that are neutral for a new modifier allele New mutation rates survive if and only if they fall below this surface—a generalization of the hyperplane found by Zhivotovsky et al Proc Natl Acad Sci USA 91 1079–1083 1994 for a multilocus recombination modifier Increases in mutation rates at some loci may evolve if compensated for by decreases at other loci The strength of selection on the modifier scales in proportion to the number of germline cell divisions and increases with the number of loci affected Loci that do not make a difference to marginal fitnesses at equilibrium are not subject to the reduction principle and under fine tuning of mutation rates would be expected to have higher mutation rates than loci in mutationselection balanceOther results include the nonexistence of ‘viability analogous Hardy–Weinberg’ modifier polymorphisms under multiplicative mutation and the sufficiency of average transmission rates to encapsulate the effect of modifier polymorphisms on the transmission of loci under selection A conjecture is offered regarding situations like recombination in the presence of mutation that exhibit departures from the reduction principle Constraints for tractability are tight linkage of all loci initial fixation at the modifier locus and mutation distributions comprising transition probabilities of reversible Markov chains
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