The distribution of fitness effects of nonsynonymous mutations varies phylogenetically across animals
13 affiliations
- 1Department of Ecology and Evolutionary Biology, University of California, Los Angeles, Los Angeles, California, United States of America
- 2Department of Integrative Biology, University of California, Berkeley, Berkeley, California, United States of America
- 3Center for Evolution and Medicine, School of Human Evolution and Social Change, Arizona State University, Tempe, Arizona, United States of America
- 4Advanced Genomics Unit, National Laboratory of Genomics for Biodiversity (Langebio), Center for Research and Advanced Studies (Cinvestav), Irapuato, Guanajuato, Mexico
- 5Department of Biological Sciences, California State University San Marcos, San Marcos, California, United States of America
- 6Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America
- 7Centro de Ciencias Genómicas, Universidad Nacional Autónoma de México (UNAM), Cuernavaca, Morelos, Mexico
- 8Bioinformatics Interdepartmental Program, University of California, Los Angeles, Los Angeles, California, United States of America
- 9Department of Ecology and Evolutionary Biology, Princeton University, Princeton, New Jersey, United States of America
- 10Conservation Genetics, San Diego Zoo Wildlife Alliance, Escondido, California, United States of America
- 11Department of Biology, Pennsylvania State University, University Park, Pennsylvania, United States of America
- 12Howard Hughes Medical Institute, Chevy Chase, Maryland, United States of America
- 13Marine Mammal and Turtle Division, Southwest Fisheries Science Center, La Jolla, California, United States of America
Abstract
The distribution of fitness effects (DFE) describes the selection coefficients of newly arising mutations and fundamentally influences population genetic processes. However, the extent and mechanisms of differences in the DFE for non-synonymous mutations have not been systematically investigated across species with divergent phylogenetic histories and ecologies. Here, we inferred the DFE in natural populations of 11 animal (sub)species, including humans, mice, fin whales, vaquitas, wolves, collared flycatchers, pied flycatchers, halictid bees, Drosophila, and mosquitoes. We found that mammals have a higher proportion of strongly deleterious mutations (defined as s≤−0.01; 22% to 47% in mammals; 0.0% to 5.4% in insects and birds) and a lower proportion of weakly deleterious mutations than insects and birds. Further, the DFE co-varies with phylogeny, such that the mean mutation effects are more similar in closely related species (Pagel’s λ = 0.84, P = 0.01). Next, we investigated whether various summary statistics of the DFE were related to variation in life-history traits across these organisms. We found some support for genome size, body mass, and long-term effective population size being correlated with the DFE. Overall, our findings are consistent with predictions derived independently from the Fisher’s Geometric Model (FGM), which defines organismal complexity as the number of phenotypes under selection. FGM predicts that mutations are more deleterious in complex organisms, while strongly deleterious mutations occur more frequently in smaller populations. Our study demonstrates strong phylogenetic signal in the evolution of a fundamental population genetics parameter, and proposes that, through mechanisms of epistasis, long-term population size and organismal complexity could be underlying variation in the DFE across animals.
The distribution of fitness effects (DFE) describes the impact of mutations on an organism’s ability to reproduce, but how and why does the DFE vary among species? This study analyzes genetic variation from 11 animal species, finding that fitness effects are influenced by phylogeny, population size and organismal complexity.
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BibTeX
@article{lin2026distribution,
title = {{The distribution of fitness effects of nonsynonymous mutations varies phylogenetically across animals}},
author = {Meixi Lin and Sneha Chakraborty and Carlos Eduardo G. Amorim and Sergio F. Nigenda-Morales and Annabel C. Beichman and Paulina G. Nuñez-Valencia and Jonathan C. Mah and Jacqueline A. Robinson and Christopher C. Kyriazis and Christian D. Huber and Andrew E. Webb and Sarah D. Kocher and Frederick I. Archer and Andrés Moreno-Estrada and Robert K. Wayne and Kirk E. Lohmueller},
journal = {PLOS Biology},
year = {2026},
month = sep,
doi = {10.1371/journal.pbio.3003976},
url = {https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003976},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The distribution of fitness effects of nonsynonymous mutations varies phylogenetically across animals
AU - Meixi Lin
AU - Sneha Chakraborty
AU - Carlos Eduardo G. Amorim
AU - Sergio F. Nigenda-Morales
AU - Annabel C. Beichman
AU - Paulina G. Nuñez-Valencia
AU - Jonathan C. Mah
AU - Jacqueline A. Robinson
AU - Christopher C. Kyriazis
AU - Christian D. Huber
AU - Andrew E. Webb
AU - Sarah D. Kocher
AU - Frederick I. Archer
AU - Andrés Moreno-Estrada
AU - Robert K. Wayne
AU - Kirk E. Lohmueller
PY - 2026
DA - 2026/09/08
JO - PLOS Biology
DO - 10.1371/journal.pbio.3003976
UR - https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003976
AB - The distribution of fitness effects (DFE) describes the selection coefficients of newly arising mutations and fundamentally influences population genetic processes. However, the extent and mechanisms of differences in the DFE for non-synonymous mutations have not been systematically investigated across species with divergent phylogenetic histories and ecologies. Here, we inferred the DFE in natural populations of 11 animal (sub)species, including humans, mice, fin whales, vaquitas, wolves, collared flycatchers, pied flycatchers, halictid bees, Drosophila, and mosquitoes. We found that mammals have a higher proportion of strongly deleterious mutations (defined as s≤−0.01; 22% to 47% in mammals; 0.0% to 5.4% in insects and birds) and a lower proportion of weakly deleterious mutations than insects and birds. Further, the DFE co-varies with phylogeny, such that the mean mutation effects are more similar in closely related species (Pagel’s λ = 0.84, P = 0.01). Next, we investigated whether various summary statistics of the DFE were related to variation in life-history traits across these organisms. We found some support for genome size, body mass, and long-term effective population size being correlated with the DFE. Overall, our findings are consistent with predictions derived independently from the Fisher’s Geometric Model (FGM), which defines organismal complexity as the number of phenotypes under selection. FGM predicts that mutations are more deleterious in complex organisms, while strongly deleterious mutations occur more frequently in smaller populations. Our study demonstrates strong phylogenetic signal in the evolution of a fundamental population genetics parameter, and proposes that, through mechanisms of epistasis, long-term population size and organismal complexity could be underlying variation in the DFE across animals. The distribution of fitness effects (DFE) describes the impact of mutations on an organism’s ability to reproduce, but how and why does the DFE vary among species? This study analyzes genetic variation from 11 animal species, finding that fitness effects are influenced by phylogeny, population size and organismal complexity.
SN - 1545-7885
ER -