1. Evolutionary Biology
  2. Genetics and Genomics
Download icon

The distribution of fitness effects among synonymous mutations in a gene under directional selection

  1. Eleonore Lebeuf-Taylor
  2. Nick McCloskey
  3. Susan F Bailey
  4. Aaron Hinz
  5. Rees Kassen  Is a corresponding author
  1. University of Ottawa, Canada
  2. Clarkson University, United States
Research Article
  • Cited 6
  • Views 3,417
  • Annotations
Cite this article as: eLife 2019;8:e45952 doi: 10.7554/eLife.45952

Abstract

The fitness effects of synonymous mutations, nucleotide changes that do not alter the encoded amino acid, have often been assumed to be neutral, but a growing body of evidence suggests otherwise. We used site-directed mutagenesis coupled with direct measures of competitive fitness to estimate the distribution of fitness effects among synonymous mutations for a gene under directional selection and capable of adapting via synonymous nucleotide changes. Synonymous mutations had highly variable fitness effects, both deleterious and beneficial, resembling those of nonsynonymous mutations in the same gene. This variation in fitness was underlain by changes in transcription linked to the creation of internal promoter sites. A positive correlation between fitness and the presence of synonymous substitutions across a phylogeny of related Pseudomonads suggests these mutations may be common in nature. Taken together, our results provide the most compelling evidence to date that synonymous mutations with non-neutral fitness effects may in fact be commonplace.

Data availability

Genomic data has been deposited into the NCBI Sequence Read Archive as BioProject PRJNA515918. All other data generated during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 1, 2, and 3.

The following data sets were generated

Article and author information

Author details

  1. Eleonore Lebeuf-Taylor

    Department of Biology, University of Ottawa, Ottawa, Canada
    Competing interests
    The authors declare that no competing interests exist.
  2. Nick McCloskey

    Department of Biology, University of Ottawa, Ottawa, Canada
    Competing interests
    The authors declare that no competing interests exist.
  3. Susan F Bailey

    Department of Biology, Clarkson University, Potsdam, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2294-1229
  4. Aaron Hinz

    Department of Biology, University of Ottawa, Ottawa, Canada
    Competing interests
    The authors declare that no competing interests exist.
  5. Rees Kassen

    Department of Biology, University of Ottawa, Ottawa, Canada
    For correspondence
    rees.kassen@uottawa.ca
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5617-4259

Funding

Natural Sciences and Engineering Research Council of Canada (Discovery Grant)

  • Rees Kassen

Natural Sciences and Engineering Research Council of Canada (Canada Graduate Scholarship)

  • Eleonore Lebeuf-Taylor

Ontario Ministry of Economic Development and Innovation (Ontario Graduate Scholarship)

  • Nick McCloskey

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Christian R Landry, Université Laval, Canada

Publication history

  1. Received: February 10, 2019
  2. Accepted: July 18, 2019
  3. Accepted Manuscript published: July 19, 2019 (version 1)
  4. Version of Record published: August 13, 2019 (version 2)

Copyright

© 2019, Lebeuf-Taylor et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 3,417
    Page views
  • 400
    Downloads
  • 6
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Developmental Biology
    2. Evolutionary Biology
    Colton M Unger et al.
    Research Article Updated

    Bones in the vertebrate cranial base and limb skeleton grow by endochondral ossification, under the control of growth plates. Mechanisms of endochondral ossification are conserved across growth plates, which increases covariation in size and shape among bones, and in turn may lead to correlated changes in skeletal traits not under direct selection. We used micro-CT and geometric morphometrics to characterize shape changes in the cranium of the Longshanks mouse, which was selectively bred for longer tibiae. We show that Longshanks skulls became longer, flatter, and narrower in a stepwise process. Moreover, we show that these morphological changes likely resulted from developmental changes in the growth plates of the Longshanks cranial base, mirroring changes observed in its tibia. Thus, indirect and non-adaptive morphological changes can occur due to developmental overlap among distant skeletal elements, with important implications for interpreting the evolutionary history of vertebrate skeletal form.

    1. Evolutionary Biology
    Anjali M Prabhat et al.
    Research Article

    The evolution of bipedalism and reduced reliance on arboreality in hominins resulted in larger lower limb joints relative to the joints of the upper limb. The pattern and timing of this transition, however, remains unresolved. Here, we find the limb joint proportions of Australopithecus afarensis, Homo erectus, and Homo naledi to resemble those of modern humans, whereas those of A. africanus, Australopithecus sediba, Paranthropus robustus, Paranthropus boisei, Homo habilis, and Homo floresiensis are more ape-like. The homology of limb joint proportions in A. afarensis and modern humans can only be explained by a series of evolutionary reversals irrespective of differing phylogenetic hypotheses. Thus, the independent evolution of modern human-like limb joint proportions in A. afarensis is a more parsimonious explanation. Overall, these results support an emerging perspective in hominin paleobiology that A. afarensis was the most terrestrially adapted australopith despite the importance of arboreality throughout much of early hominin evolution.