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Weakest link epistasis and the geometry of genetic load

Labourel, F.; Bansept, F.; McCandlish, D. M.

2025-12-09 evolutionary biology
10.64898/2025.12.08.693057 bioRxiv
Show abstract

Because natural selection must optimise multiple traits at once, previous work has suggested that phenotypic dimensionality can substantially worsen the equilibrium fitness defect of a population relative to the phenotypic optimum. However, it remains unclear how conclusions drawn from classical theoretical phenotype-fitness maps extend to models grounded in explicit biological mechanisms. Here we introduce weakest-link epistasis (WLE), a framework in which fitness is determined by the least-fit phenotypic component, an extreme form of diminishing returns epistasis. We show that in this framework, increasing dimensionality amplifies the load in a manner comparable to, but surprisingly not more than, Fishers geometric model (FGM). Building on this similarity, we demonstrate why genetic load is often invariant across different rules for combining trait-specific fitness components into an overall organismal fitness. We explore these ideas by considering the family of models where the organismal fitness is determined based on the{ell} p-norm of the vector of trait-specific fitness defects, a framework that includes both FGM and WLE, but also captures a continuum of genetic architectures, ranging from generalist to specialist regimes. Altogether, our approach proposes a new perspective on the geometry of adaptive landscapes, and may help provide quantitative insight into the cost of complexity.

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