The approach to mutation–selection balance in an infinite asexual population, and the evolution of mutation rates

A method is described for calculating the dynamics of the distribution of fitness in an infinite asexual population which is subject to unconditionally deleterious mutations with independent effects. This method is applied to the problem of calculating the frequency of a mutator subpopulation, at equilibrium between mutation and indirect selection due to association with deleterious mutations. Many mutator alleles are produced by loss–of–function mutations in polymerase or mismatch repair genes. Previous calculations have ignored the fact that this creates a flux of higher fitness individuals into the mutator subpopulation. This flux raises the mean fitness of the mutator subpopulation, and when this factor is taken into account, the frequency of the mutator may be more than an order of magnitude greater than recent theoretical work has suggested.

[1]  R. A. Fisher,et al.  The Genetical Theory of Natural Selection , 1931 .

[2]  K. Atwood,et al.  Selective mechanisms in bacteria. , 1951, Cold Spring Harbor symposia on quantitative biology.

[3]  M. Kimura.  A stochastic model concerning the maintenance of genetic variability in quantitative characters. , 1965, Proceedings of the National Academy of Sciences of the United States of America.

[4]  M. Kimura,et al.  The mutational load with epistatic gene interactions in fitness. , 1966, Genetics.

[5]  M. Kimura,et al.  The average number of generations until extinction of an individual mutant gene in a finite population. , 1969, Genetics.

[6]  E. Leigh,et al.  Natural Selection and Mutability , 1970, The American Naturalist.

[7]  T. Ohta.  Slightly Deleterious Mutant Substitutions in Evolution , 1973, Nature.

[8]  P. Painter.  Mutator genes and selection for the mutation rate in bacteria. , 1975, Genetics.

[9]  J. Haigh.  The accumulation of deleterious genes in a population--Muller's Ratchet. , 1978, Theoretical population biology.

[10]  M. Kimura.  Model of effectively neutral mutations in which selective constraint is incorporated. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[11]  M. Gross,et al.  Incidence of mutator strains in Escherichia coli and coliforms in nature. , 1981, Mutation research.

[12]  L. Chao,et al.  COMPETITION BETWEEN HIGH AND LOW MUTATING STRAINS OF ESCHERICHIA COLI , 1983, Evolution; international journal of organic evolution.

[13]  M. Turelli.  Heritable genetic variation via mutation-selection balance: Lerch's zeta meets the abdominal bristle. , 1984, Theoretical population biology.

[14]  Thomas B. L. Kirkwood,et al.  Accuracy in molecular processes : its control and relevance to living systems , 1986 .

[15]  W. G. Hill,et al.  Quantitative genetic variability maintained by mutation-stabilizing selection balance in finite populations. , 1988, Genetical research.

[16]  J Ninio,et al.  Transient mutators: a semiquantitative analysis of the influence of translation and transcription errors on mutation rates. , 1991, Genetics.

[17]  T. Ohta.  THE NEARLY NEUTRAL THEORY OF MOLECULAR EVOLUTION , 1992 .

[18]  J. Drake.  General antimutators are improbable. , 1993, Journal of molecular biology.

[19]  A. Kondrashov.  MODIFIERS OF MUTATION-SELECTION BALANCE - GENERAL-APPROACH AND THE EVOLUTION OF MUTATION-RATES , 1995 .

[20]  N. Barton.  Linkage and the limits to natural selection. , 1995, Genetics.

[21]  W. L. Payne,et al.  High Mutation Frequencies Among Escherichia coli and Salmonella Pathogens , 1996, Science.

[22]  Michael Lynch,et al.  Estimate of the genomic mutation rate deleterious to overall fitness in E. coll , 1996, Nature.

[23]  R. Lenski,et al.  Evolution of high mutation rates in experimental populations of E. coli , 1997, Nature.

[24]  F. Taddei,et al.  To be a mutator, or how pathogenic and commensal bacteria can evolve rapidly. , 1997, Trends in microbiology.

[25]  P. Keightley,et al.  Genomic mutation rates for lifetime reproductive output and lifespan in Caenorhabditis elegans. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[26]  F. Taddei,et al.  Role of mutator alleles in adaptive evolution , 1997, Nature.

[27]  K. Dawson.  Evolutionarily stable mutation rates. , 1998, Journal of theoretical biology.

[28]  J. Drake,et al.  Rates of spontaneous mutation. , 1998, Genetics.

[29]  K. Dawson.  The dynamics of infinitesimally rare alleles, applied to the evolution of mutation rates and the expression of deleterious mutations. , 1999, Theoretical population biology.

[30]  R George,et al.  An exploration of the sequence of a 2.9-Mb region of the genome of Drosophila melanogaster: the Adh region. , 1999, Genetics.

[31]  P. Keightley,et al.  New estimates of the rates and effects of mildly deleterious mutation in Drosophila melanogaster. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[32]  T. Johnson.  Beneficial mutations, hitchhiking and the evolution of mutation rates in sexual populations. , 1999, Genetics.

[33]  Hervé Le Nagard,et al.  Mutators, population size, adaptive landscape and the adaptation of asexual populations of bacteria. , 1999, Genetics.

[34]  A. D. Peters,et al.  High frequency of cryptic deleterious mutations in Caenorhabditis elegans. , 1999, Science.