The impact of Fisher's reproductive compensation on raising equilibrium frequencies of semidominant, nonlethal mutations under mutation/selection balance

Hastings, Ian ORCID: https://orcid.org/0000-0002-1332-742X (2023) 'The impact of Fisher's reproductive compensation on raising equilibrium frequencies of semidominant, nonlethal mutations under mutation/selection balance'. G3: Genes, Genomes, Genetics, Vol 14, Issue 1, jkad231.

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Abstract

Fisher's reproductive compensation (fRC) occurs when a species’ demography means the death of an individual results in increased survival probability of his/her relatives, usually assumed to be full sibs. This likely occurs in many species, including humans. Several important recessive human genetic diseases cause early foetal/infant death allowing fRC to act on these mutations. The impact of fRC on these genetic conditions has been previously calculated and shown to be substantial as quantified by ω, the fold increase in equilibrium frequencies of the mutation under fRC compared with its absence, i.e. ω = 1.22 and ω = 1.33 for autosomal and sex-linked loci, respectively. However, the impact of fRC on the frequency of the much larger class of semidominant, nonlethal mutations is unknown. This is calculated here as ω = 2 − h*s for autosomal loci and ω up to 2 for sex-linked loci where h is dominance (varied between 0.05 and 0.95) and s is selection coefficient (varied between 0.05 and 0.9). These results show that the actions of fRC can almost double the equilibrium frequency of deleterious mutations with low values of h and/or s (noting that “low” is s∼0.05 to 0.1). It is noted that fRC may act differentially across the genome with genes expressed early in life being fully exposed to fRC while those expressed later in life may be unaffected; this could lead to systematic differences in deleterious allele frequency across the genome.

Item Type:	Article
Subjects:	QU Biochemistry > Genetics > QU 460 Genomics. Proteomics
Faculty: Department:	Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI):	https://doi.org/10.1093/g3journal/jkad231
Depositing User:	Clare O'Neill
Date Deposited:	28 Nov 2023 14:32
Last Modified:	16 Feb 2024 15:39
URI:	https://archive.lstmed.ac.uk/id/eprint/23562

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