Purifying selection, drift and reversible mutation with arbitrarily high mutation rates

TL;DR

This paper develops a population genetics model that accounts for high mutation rates, purifying selection, and genetic drift, revealing increased intermediate variants and potential for rapid evolution, impacting studies of genetic and epigenetic diversity.

Contribution

It introduces an analytical model incorporating high mutation rates and reversible mutations, extending standard population genetics theory to hyperdiverse populations.

Findings

More intermediate frequency variants than standard models predict

Evolution rates can approach or surpass neutral rates under purifying selection

Implications for interpreting genetic and epigenetic variation studies

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 (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.