Comparison of the Full Distribution of Fitness Effects of New Amino Acid Mutations Across Great Apes

TY - JOUR

T1 - Comparison of the Full Distribution of Fitness Effects of New Amino Acid Mutations Across Great Apes

AU - Castellano, David

AU - Macià, Moisès Coll

AU - Tataru, Paula

AU - Bataillon, Thomas

AU - Munch, Kasper

N1 - Copyright © 2019, Genetics.

PY - 2019

Y1 - 2019

N2 - The distribution of fitness effects (DFE) is central to many questions in evolutionary biology. However, little is known about the differences in DFEs between closely related species. We use more than 9,000 coding genes orthologous one-to-one across great apes, gibbons, and macaques to assess the stability of the DFE across great apes. We use the unfolded site frequency spectrum of polymorphic mutations (n = 8 haploid chromosomes per population) to estimate the DFE. We find that the shape of the deleterious DFE is strikingly similar across great apes. We confirm that effective population size (Ne ) is a strong predictor of the strength of negative selection, consistent with the Nearly Neutral Theory. However, we also find that the strength of negative selection varies more than expected given the differences in Ne between species. Across species, mean fitness effects of new deleterious mutations co-varies with Ne , consistent with positive epistasis among deleterious mutations. We find that the strength of negative selection for the smallest populations: bonobos and western chimpanzees, is higher than expected given their Ne This may result from a more efficient purging of strongly deleterious recessive variants in these populations. Forward simulations confirm that these findings are not artefacts of the way we are inferring Ne and DFE parameters. All findings are replicated using only GC-conservative mutations, thereby confirming that GC-biased gene conversion is not affecting our conclusions.

AB - The distribution of fitness effects (DFE) is central to many questions in evolutionary biology. However, little is known about the differences in DFEs between closely related species. We use more than 9,000 coding genes orthologous one-to-one across great apes, gibbons, and macaques to assess the stability of the DFE across great apes. We use the unfolded site frequency spectrum of polymorphic mutations (n = 8 haploid chromosomes per population) to estimate the DFE. We find that the shape of the deleterious DFE is strikingly similar across great apes. We confirm that effective population size (Ne ) is a strong predictor of the strength of negative selection, consistent with the Nearly Neutral Theory. However, we also find that the strength of negative selection varies more than expected given the differences in Ne between species. Across species, mean fitness effects of new deleterious mutations co-varies with Ne , consistent with positive epistasis among deleterious mutations. We find that the strength of negative selection for the smallest populations: bonobos and western chimpanzees, is higher than expected given their Ne This may result from a more efficient purging of strongly deleterious recessive variants in these populations. Forward simulations confirm that these findings are not artefacts of the way we are inferring Ne and DFE parameters. All findings are replicated using only GC-conservative mutations, thereby confirming that GC-biased gene conversion is not affecting our conclusions.

KW - DFE

KW - beneficial mutations

KW - compensatory evolution

KW - deleterious mutations

KW - effective population size

KW - epistasis

UR - http://www.scopus.com/inward/record.url?scp=85074553077&partnerID=8YFLogxK

U2 - 10.1534/genetics.119.302494

DO - 10.1534/genetics.119.302494

M3 - Journal article

C2 - 31488516

SN - 1943-2631

VL - 213

SP - 953

EP - 966

JO - Genetics

JF - Genetics

IS - 3

ER -