A gene-based model of fitness and its implications for genetic variation: linkage disequilibrium.

ABSTRACT: A widely used model of the effects of mutations on fitness (the "sites" model) assumes that heterozygous recessive or partially recessive deleterious mutations at different sites in a gene complement each other, similarly to mutations in different genes. However, the general lack of complementation between major effect allelic mutations suggests an alternative possibility, which we term the "gene" model. This model assumes that a pair of heterozygous deleterious mutations in trans behave effectively as homozygotes, so that the fitness of trans-heterozygotes are lower than those of cis-heterozygotes. We examine the properties of the two different models, using both analytical and simulation methods. We show that the gene model predicts positive linkage disequilibrium (LD) between deleteriou

SUBMITTER: Johri P 

PROVIDER: S-EPMC12606437 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature