Genotype by random environmental interactions gives an advantage to non-favored minor alleles

Abstract

Fixation probability, the probability that the frequency of a newly arising mutation in a population will eventually reach unity, is a fundamental quantity in evolutionary genetics. Here we use a number of models (several versions of the Moran model and the haploid Wright-Fisher model) to examine fixation probabilities for a constant size population where the fitness is a random function of both allelic state and spatial position, despite neither allele being favored on average. The concept of fitness varying with respect to both genotype and environment is important in models of cancer initiation and progression, bacterial dynamics, and drug resistance. Under our model spatial heterogeneity redefines the notion of neutrality for a newly arising mutation, as such mutations fix at a higher rate than that predicted under neutrality. The increased fixation probability appears to be due to rare alleles having an advantage. The magnitude of this effect can be large, and is an increasing function of the spatial variance and skew in fitness. The effect is largest when the fitness values of the mutants and wild types are anti-correlated across environments. We discuss results for both a spatial ring geometry of cells (such as that of a colonic crypt), a 2D lattice and a mass-action (complete graph) arrangement.