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Insufficient evidence for non-neutrality of synonymous mutations

Nature volume 616, pages E8–E9 (2023)Cite this article

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The Original Article was published on 08 June 2022

arising from X. Shen et al. Nature https://www.nature.com/articles/s41586-022-04823-w (2022)

Many lines of evidence accumulated over decades of research have shown that, because they do not lead to sequence changes in proteins, synonymous mutations are much less likely than nonsynonymous ones to have biological effects1, although exceptions exist2,3,4. In a recent paper5, Shen et al. claimed that most synonymous mutations in the coding regions of 21 yeast genes were deleterious. We argue that, owing to technical issues with the experimental design and replication, this claim is not supported by the data reported by Shen et al.5.

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Fig. 1: Schematic of the approach taken by Shen et al. for strain creation.

Data availability

Data discussed are from Shen et al.5.

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Authors and Affiliations

  1. Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA

    Leonid Kruglyak & Joshua S. Bloom

  2. Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA, USA

    Leonid Kruglyak & Joshua S. Bloom

  3. Howard Hughes Medical Institute, Chevy Chase, MD, USA

    Leonid Kruglyak & Joshua S. Bloom

  4. Cluster of Excellence on Cellular Stress Responses in Age-associated Diseases (CECAD), University of Cologne, Cologne, Germany

    Andreas Beyer & Jan Grossbach

  5. Institute for Genetics, Faculty of Mathematics and Natural Sciences, University of Cologne, Cologne, Germany

    Andreas Beyer & Jan Grossbach

  6. Institute for Medical Engineering and Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA

    Tami D. Lieberman & Christopher P. Mancuso

  7. Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA

    Tami D. Lieberman & Christopher P. Mancuso

  8. Department of Biology, University of Utah, Salt Lake City, UT, USA

    Matthew S. Rich

  9. Department of Genetics, Stanford University, Stanford, CA, USA

    Gavin Sherlock

  10. Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA, USA

    Craig D. Kaplan

Authors
  1. Leonid Kruglyak
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  2. Andreas Beyer
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  3. Joshua S. Bloom
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  4. Jan Grossbach
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  9. Craig D. Kaplan
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Contributions

All of the authors discussed and conceived the response. L.K. and C.D.K. wrote initial draft with feedback from all of the authors. G.S. and M.S.R. conceived the figure with comments and feedback from all of the authors. L.K. and C.D.K. revised the manuscript in consultation with all of the authors.

Corresponding authors

Correspondence to Leonid Kruglyak or Craig D. Kaplan.

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Kruglyak, L., Beyer, A., Bloom, J.S. et al. Insufficient evidence for non-neutrality of synonymous mutations. Nature 616, E8–E9 (2023). https://doi.org/10.1038/s41586-023-05865-4

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Comments

Commenting on this article is now closed.

  1. Jianzhi Zhang

    We thank Kruglyak and colleagues for their critique of Shen et al. (2022). We are performing additional experiments to address their concerns and will reply after the completion of these experiments.

  2. Ditipriya Chakraborty

    love this topic if you wish you can visit our website https://www.creativeauthor.....

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