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The impact of Fishers Reproductive Compensation on raising equilibrium frequencies of semi-dominant, non-lethal mutations under mutation/selection balance.

Hastings, I. M.

2021-11-23 genetics
10.1101/2021.11.19.469230 bioRxiv
Show abstract

Fishers reproductive compensation (fRC) occurs when a species demography means the death of an individual allows increased survival 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 calculated and shown to be substantial as quantified by {omega}, the fold increase in equilibrium frequencies of the mutation under fRC compared to its absence i.e. {omega}=1.22 and {omega}=1.33 for autosomal and sex-linked loci, respectively. However, the impact of fRC on the frequency of the much large class of semi-dominant, non-lethal mutations is unknown. This is calculated here by a mixture of simulation and algebra and shown that {omega}=2-h*s and {omega}{approx}2-0.19s-0.85h*s for autosomal and sex-linked loci respectively 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 equilibrium frequency of mutations with low values of h and/or s. The dynamics of fRC acting on this type of mutation are also identified and discussed.

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