title: Purifying selection, drift, and reversible mutation with arbitrarily high mutation rates.
abstract: Some species exhibit very high levels of DNA sequence variability; there is also evidence for the existence of heritable epigenetic variants that experience state changes at a much higher rate than sequence variants. In both cases, the resulting high diversity levels within a population (hyperdiversity) mean that standard population genetics methods are not trustworthy. We analyze a population genetics model that incorporates purifying selection, reversible mutations, and genetic drift, assuming a stationary population size. We derive analytical results for both population parameters and sample statistics and discuss their implications for studies of natural genetic and epigenetic variation. In particular, we find that (1) many more intermediate-frequency variants are expected than under standard models, even with moderately strong purifying selection, and (2) rates of evolution under purifying selection may be close to, or even exceed, neutral rates. These findings are related to empirical studies of sequence and epigenetic variation.
authors.affiliation: Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FL, United Kingdom Brian.Charlesworth@ed.ac.uk.
authors.forename: Brian
authors.initials: B
authors.lastname: Charlesworth
authors.affiliation: Theoretical Sciences Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore 560064, India.
authors.forename: Kavita
authors.initials: K
authors.lastname: Jain
mesh_terms: D000465:Algorithms; D019143:Evolution, Molecular; D040961:Genetic Drift; D005828:Genetics, Population; D008957:Models, Genetic; D009154:Mutation; D059645:Mutation Rate; D012641:Selection, Genetic
keywords: epigenetic variation; hyperdiversity; purifying selection; rate of substitution; site frequency spectrum