Early-life viability selection targets deleterious mutations in exons

Chen, Rebecca S. ORCID: https://orcid.org/0000-0002-9364-3771; Soulsbury, Carl D.; van Oers, Kees; Hoffman, Joseph I. ORCID: https://orcid.org/0000-0001-5895-8949. 2025 Early-life viability selection targets deleterious mutations in exons. Current Biology, 35 (23). 5908-5914.e4. 10.1016/j.cub.2025.10.043

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Abstract/Summary

Understanding how deleterious mutations affect fitness is central to evolutionary and conservation biology. However, most empirical studies rely on inbreeding as a proxy for the mutation load, overlooking the substantial contribution of deleterious mutations expressed in the heterozygous state. Moreover, although mutations in coding and non-coding regions of the genome are hypothesized to have qualitatively different fitness effects and thus experience distinct selective pressures, such functional heterogeneity is often overlooked. Selection may also vary across life stages, adding a temporal dimension that is seldom captured. Using whole-genome resequencing data from the black grouse (Lyrurus tetrix), we predicted deleterious mutations using evolutionary conservation and functional predictions. We then used the resulting genomic mutation load estimates to quantify viability selection at functionally distinct genomic regions across three life-history stages: chicks, yearlings, and adults. We found that viability selection is strongest early in life and mainly targets deleterious mutations at evolutionarily conserved sites. Specifically, early-life selection predominantly acts against deleterious mutations located in exons, contrasting with our previous finding that sexual selection in this species targets deleterious mutations in regulatory regions. These results show that the fitness effects of deleterious mutations are neither temporally constant nor uniformly distributed across the genome. Instead, they reflect dynamic selection regimes that shift across both life-history stages and genomic contexts. Our findings refine our understanding of evolutionary dynamics and life-history evolution, while also informing the use of genomic fitness indicators in biological conservation.

Item Type:	Publication - Article
Digital Object Identifier (DOI):	10.1016/j.cub.2025.10.043
ISSN:	09609822
Additional Keywords:	mutation load, predicted deleterious mutations, inbreeding depression, viability selection, coding mutations, life-history evolution, conservation, genetic load
Date made live:	01 Dec 2025 16:40 +0 (UTC)
URI:	https://nora.nerc.ac.uk/id/eprint/540686

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