Estimating the fitness effects of new mutations in the wild yeast Saccharomyces paradoxus
File(s)
Published version
Author(s)
Koufopanou, V
Lomas, S
Tsai, IJ
Burt, A
Type
Journal Article
Abstract
The nature of selection acting on a population is in large measure determined by the distribution of fitness effects of new mutations. In this study, we use DNA sequences from four closely related clades of Saccharomyces paradoxus and Saccharomyces cerevisiae to identify and polarize new mutations and estimate their fitness effects. By progressively restricting the analyses to narrower categories of sites, we further seek to characterize sites with predictable mutational effects, that is, unconditionally deleterious, neutral or beneficial. Consistent with previous studies on S. paradoxus, we have failed to find evidence for mutations with beneficial effects, even in regions that were divergent in two outgroup clades, perhaps a consequence of the relatively unchallenged, predominantly asexual and highly inbred lifestyle of this species. On the other hand, there is abundant evidence of deleterious mutations, varying in severity of effect from strongly deleterious to very mild, particularly in regions conserved in the outgroup taxa, indicating a history of persistent purifying selection. Narrowing the analysis down to individual amino acids reduces further the range of effects: for example, mutations changing cysteine are predicted to be nearly always strongly deleterious, whereas those changing arginine, serine, and tyrosine are expected to be nearly neutral. The proportion of mutations with deleterious effects for a particular amino acid is correlated with long-term stasis of that amino acid among highly divergent sequences from a variety of organisms, showing that functionality of sites tends to persist through the diversification of clades and that our findings are also relevant to longer evolutionary times and other taxa.
Date Issued
2015-06-16
Date Acceptance
2015-06-11
Citation
Genome Biology and Evolution, 2015, 7 (7), pp.1887-1895
ISSN
1759-6653
Publisher
Oxford University Press
Start Page
1887
End Page
1895
Journal / Book Title
Genome Biology and Evolution
Volume
7
Issue
7
Copyright Statement
© The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000358800500004&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Evolutionary Biology
Genetics & Heredity
purifying selection
derived allele frequency
deleterious mutations
fitness effects of mutations
ADAPTIVE MOLECULAR EVOLUTION
DROSOPHILA-MELANOGASTER
CAENORHABDITIS-ELEGANS
DELETERIOUS MUTATIONS
POPULATION GENOMICS
SELECTION
GENETICS
GENES
SIZE
Alleles
Amino Acids
Codon
Evolution, Molecular
Genetic Fitness
Models, Genetic
Mutation
Nucleotides
Phylogeny
Polymorphism, Genetic
Saccharomyces
Developmental Biology
0604 Genetics
0603 Evolutionary Biology
Publication Status
Published