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Brian Charlesworth

Publications and source records attributed to Brian Charlesworth.

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The rights and wrongs of rescaling in population genetics simulations

Computer simulations of complex population genetic models are an essential tool for making sense of the large-scale datasets of multiple genome sequences from a single species that are becoming increasingly available. A widely used approach for reducing computing time is to simulate populations that are much smaller than the natural populations that they are intended to represent, by using parameters such as selection coefficients and mutation rates whose products with the population size correspond to those of the natural populations. This approach has come to be known as rescaling, and is justified by the theory of the genetics of finite populations. Recently, however, there have been criticisms of this practice, which have brought to light situations in which it can lead to erroneous conclusions. This paper reviews the theoretical basis for rescaling, and relates it to current practice in population genetics simulations. It shows that some population genetic statistics are scaleable while others are not. Additionally, it shows that there are likely to be problems with rescaling when simulating large chromosomal regions, due to the non-linear relation between the physical distance between a pair of separate nucleotide sites and the frequency of recombination between them. Other difficulties with rescaling can arise in connection with simulations of selection on complex traits, and with populations that reproduce partly by self-fertilization or asexual reproduction. A number of recommendations are made for good practice in relation to rescaling.

q-bio.PE

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

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.

q-bio.PE