A comprehensive representation of selection at loci with multiple alleles that allows complex forms of genotypic fitness

TL;DR

This paper introduces a flexible analytical framework for modeling selection at multiallelic loci, accommodating complex fitness interactions and diverse genetic scenarios, thereby extending classical population genetics theory beyond biallelic assumptions.

Contribution

It provides the first comprehensive expression for the force of selection at multiallelic loci with complex fitness functions, enhancing understanding of genetic diversity's role in evolution.

Findings

Framework supports arbitrary number of alleles and fitness forms

Enables analysis of frequency-dependent and heterozygote advantage scenarios

Facilitates more realistic modeling of genetic diversity in populations

Abstract

Genetic diversity is central to the process of evolution. Both natural selection and random genetic drift are influenced by the level of genetic diversity of a population; selection acts on diversity while drift samples from it. At a given locus in a diploid population, each individual carries only two alleles, but the population as a whole can possess a much larger number of alleles, with the upper limit constrained by twice the population size. This allows for many possible types of homozygotes and heterozygotes. Moreover, there are biologically important loci, for example those related to the MHC complex, the ABO blood types, and cystic fibrosis, that exhibit a large number of alleles. Despite this, much of population genetic theory, and data analysis, are limited to considering biallelic loci. However, to the present, what is lacking is a flexible expression for the force of selection that allows an arbitrary number of alleles (and hence an arbitrary number of heterozygotes), along with a variety of forms of fitness. In this work, we remedy this absence by giving an analytical representation of the force of selection that emphasises the very different roles played by the diversity of the population, and the fitnesses of different genotypes. The result presented facilitates our understanding and applies in a variety of different situations involving multiple alleles. This includes situations where fitnesses are: additive, multiplicative, randomly fluctuating, frequency-dependent, and it allows fitnesses which involve explicit gene interactions, such as heterozygote advantage.