The rights and wrongs of rescaling in population genetics simulations

TL;DR

This paper examines the theoretical foundations and practical issues of rescaling in population genetics simulations, highlighting when it is valid and when it can lead to errors.

Contribution

It clarifies which population genetic statistics are scaleable and discusses potential pitfalls of rescaling in complex scenarios, offering guidelines for best practices.

Findings

Some genetic statistics are scaleable while others are not.

Rescaling can cause errors in large chromosomal region simulations.

Problems may arise in modeling selection on complex traits and certain reproductive modes.

Abstract

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.