Quantifying the fraction of new mutations that are recessive lethal.

Autor:	Wade EE; Department of Ecology and Evolutionary Biology, University of California-Los Angeles, Los Angeles, CA, United States.; Department of Computer Science and Engineering, Mississippi State University, Starkville, MS, United States., Kyriazis CC; Department of Ecology and Evolutionary Biology, University of California-Los Angeles, Los Angeles, CA, United States., Cavassim MIA; Department of Ecology and Evolutionary Biology, University of California-Los Angeles, Los Angeles, CA, United States., Lohmueller KE; Department of Ecology and Evolutionary Biology, University of California-Los Angeles, Los Angeles, CA, United States.; Interdepartmental Program in Bioinformatics, University of California-Los Angeles, Los Angeles, CA, United States.; Department of Human Genetics, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States.
Jazyk:	angličtina
Zdroj:	Evolution; international journal of organic evolution [Evolution] 2023 Jun 29; Vol. 77 (7), pp. 1539-1549.
DOI:	10.1093/evolut/qpad061
Abstrakt:	The presence and impact of recessive lethal mutations have been widely documented in diploid outcrossing species. However, precise estimates of the proportion of new mutations that are recessive lethal remain limited. Here, we evaluate the performance of Fit∂a∂i, a commonly used method for inferring the distribution of fitness effects (DFE), in the presence of lethal mutations. Using simulations, we demonstrate that in both additive and recessive cases, inference of the deleterious nonlethal portion of the DFE is minimally affected by a small proportion (<10%) of lethal mutations. Additionally, we demonstrate that while Fit∂a∂i cannot estimate the fraction of recessive lethal mutations, Fit∂a∂i can accurately infer the fraction of additive lethal mutations. Finally, as an alternative approach to estimate the proportion of mutations that are recessive lethal, we employ models of mutation-selection-drift balance using existing genomic parameters and estimates of segregating recessive lethals for humans and Drosophila melanogaster. In both species, the segregating recessive lethal load can be explained by a very small fraction (<1%) of new nonsynonymous mutations being recessive lethal. Our results refute recent assertions of a much higher proportion of mutations being recessive lethal (4%-5%), while highlighting the need for additional information on the joint distribution of selection and dominance coefficients. (© The Author(s) 2023. Published by Oxford University Press on behalf of The Society for the Study of Evolution (SSE).)
Databáze:	MEDLINE
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