The Joint Impact of Deleterious Mutations, Dominance, and Gene Flow on Linked Neutral Variation in Structured Populations

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The Joint Impact of Deleterious Mutations, Dominance, and Gene Flow on Linked Neutral Variation in Structured Populations

Authors

Lesturgie, P.; Blanckaert, A.; Sousa, V. C.

Abstract

Most species are geographically structured, leaving characteristic signatures in neutral regions of the genome. These signatures can be distorted when neutral regions are linked to deleterious mutations. In such regions, purifying selection can reduce genetic diversity through Background Selection (BGS) or, for recessive mutations, increase diversity through Associative Overdominance (AOD). While the effect of BGS and AOD are well characterized in panmictic populations, their effects remain largely unexplored in structured populations. Here, we investigated an Isolation with Migration model using forward simulations across a range of migration, selection, dominance, and recombination parameters. We first used a genotype-based approach to quantify the effects of deleterious mutations on standard summary statistics ({pi}, Dxy, FST, DAFi). We then showed that an Ancestral Recombination Graph-based approach, tracking tree sequences from a sample of one diploid per deme, recovers the same patterns while directly relating genetic variation to the underlying coalescent processes. When recombination is sufficiently low, we found a BGS-driven regime for weakly co-dominant mutations, characterized by lower diversity and increased genetic differentiation (FST). For recessive mutations, we first identified an AOD-driven regime, characterized by increased diversity and lower FST values followed by a transition to a subsequent BGS-driven regime. Genealogies were similarly impacted by deleterious mutations: BGS shrunk coalescent times and produces a shift towards lineage sorting topologies, while AOD stretched coalescent times and produces a shift toward incomplete lineage-sorting topologies. These patterns were weakened by gene flow, with FST and topologies remaining close to expected under neutrality, while diversity and coalescence times remained robust to demography. Our results provide clear evidence of BGS, AOD, and of their transition in a structured model with gene flow. Importantly, these processes leave distinct and interpretable signatures on gene trees, highlighting the potential of ARG-based approaches for inferring linked selection and dominance in structured populations.

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