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Report of mutation biases mirroring selection in Arabidopsis thaliana unlikely to be entirely due to variant calling errors

View ORCID ProfileJ. Grey Monroe, View ORCID ProfileKevin D. Murray, Wenfei Xian, View ORCID ProfilePablo Carbonell-Bejerano, View ORCID ProfileCharles B. Fenster, View ORCID ProfileDetlef Weigel
doi: https://doi.org/10.1101/2022.08.21.504682
J. Grey Monroe
1University of California Davis, Davis, CA 95616, USA
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  • For correspondence: gmonroe@ucdavis.edu weigel@weigelworld.org
Kevin D. Murray
2Max Planck Institute for Biology Tübingen, 72076 Tübingen, Germany
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Wenfei Xian
2Max Planck Institute for Biology Tübingen, 72076 Tübingen, Germany
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Pablo Carbonell-Bejerano
2Max Planck Institute for Biology Tübingen, 72076 Tübingen, Germany
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Charles B. Fenster
3Oak Lake Field Station, South Dakota State University, Brookings, SD 57007, USA
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Detlef Weigel
2Max Planck Institute for Biology Tübingen, 72076 Tübingen, Germany
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  • For correspondence: gmonroe@ucdavis.edu weigel@weigelworld.org
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SUMMARY

It has recently been proposed that the uneven distribution of epigenomic features might facilitate reduced mutation rate in constrained regions of the Arabidopsis thaliana genome, even though previous work had shown that it would be difficult for reduced mutation rates to evolve on a gene-by-gene basis. A solution to Lynch’s equations for the barrier imposed by genetic drift on the evolution of targeted hypomutation can, however, come from epigenomic features that are enriched in certain portions of the genome, for example, coding regions of essential genes, and which simultaneously affect mutation rate. Such theoretical considerations draw on what is known about DNA repair guided by epigenomic features. A recent publication challenged these conclusions, because several mutation data sets that support a lower mutation rate in constrained regions suffered from variant calling errors. Here we show that neither homopolymer errors nor elevated mutation rates at transposable elements are likely to entirely explain reported mutation rate biases. Observed mutation biases are also supported by a meta-analysis of several independent germline mutation data sets, with complementary experimental data providing a mechanistic basis for reduced mutation rate in genes and specifically in essential genes. Finally, models derived from the drift-barrier hypothesis demonstrate that mechanisms linking DNA repair to chromatin marks and other epigenomic features can evolve in response to second-order selection on emergent mutation biases.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted August 22, 2022.
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Report of mutation biases mirroring selection in Arabidopsis thaliana unlikely to be entirely due to variant calling errors
J. Grey Monroe, Kevin D. Murray, Wenfei Xian, Pablo Carbonell-Bejerano, Charles B. Fenster, Detlef Weigel
bioRxiv 2022.08.21.504682; doi: https://doi.org/10.1101/2022.08.21.504682
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Report of mutation biases mirroring selection in Arabidopsis thaliana unlikely to be entirely due to variant calling errors
J. Grey Monroe, Kevin D. Murray, Wenfei Xian, Pablo Carbonell-Bejerano, Charles B. Fenster, Detlef Weigel
bioRxiv 2022.08.21.504682; doi: https://doi.org/10.1101/2022.08.21.504682

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