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Comment
. 2023 Jul;619(7971):E57-E60.
doi: 10.1038/s41586-023-06315-x.

Reply to: Re-evaluating evidence for adaptive mutation rate variation

J Grey Monroe  1 , Kevin D Murray  2 , Wenfei Xian  2 , Thanvi Srikant  2 , Pablo Carbonell-Bejerano  2 , Claude Becker  2 , Mariele Lensink  3 , Moises Exposito-Alonso  4   5 , Marie Klein  3 , Julia Hildebrandt  2 , Manuela Neumann  2 , Daniel Kliebenstein  3 , Mao-Lun Weng  6 , Eric Imbert  7 , Jon Ågren  8 , Matthew T Rutter  9 , Charles B Fenster  10 , Detlef Weigel  11
Affiliations
Comment

Reply to: Re-evaluating evidence for adaptive mutation rate variation

J Grey Monroe et al. Nature. 2023 Jul.
No abstract available

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Potential homopolymer bleed-through sequencing errors cannot explain differences in mutation rate.
a, The proportion of variants that are potential homopolymer bleed-through errors among all mutation calls in our original study is as least as high in gene bodies as in intergenic sequences, and contrasts with the distribution of total mutation calls. kb, kilobase. b, Homopolymers and the proportion of variants that are potential homopolymer bleed-through errors in the original study are not lower in essential genes (ESN) compared to genes with environmentally conditional (CND), morphological (MRP) and cellular or biochemical (CLB) functions, and cannot explain the distribution of actual mutation calls.
Fig. 2
Fig. 2. Joint analyses of germline mutations in several published A. thaliana mutation accumulation studies align with mechanistic models of mutation bias.
a, Reduction in genic single-nucleotide germline mutation rates compared against genomic background in multiple A. thaliana datasets (Supplementary Table 1). For our original study, only new mutations from 400 mutation accumulation lines are shown; the other mutations in that paper were already described and are shown separately here. Mutation rate reduction in genic regions is eliminated in msh2 DNA repair mutants. bp, base pair. b, Mutation rates around gene bodies (grey and green lines). Black line indicates randomly selected windows based on gene lengths. c, Mutation rates in genes classified by functional category, rates of sequence evolution, patterns of expression and estimates of selection. Significance tested with χ2 test, n = 27,206 genes, with raw P values tested against α = 0.05 (unadjusted for multiple comparisons). Data show mean values for groups ± error bars reflecting 95% confidence intervals from bootstrapping. Vg, genetic variance of gene expression; 1001G, 1001 Genomes Project; LOF, loss of function; Dn, non-synonymous divergence; Ds, synonymous divergence; Pn, non-synonymous polymorphism; Ps, synonymous polymorphism; NS, not significant. d, Somatic mutations identified with very stringent criteria and using a caller specifically designed for rare somatic mutations, Strelka2, are reduced in gene bodies of wild-type plants, but not msh6 mutants. e, Left, general mechanism proposed in ref. . Right, new knowledge regarding biochemical mechanisms underlying reduced mutation rates in gene bodies established by recent discoveries in plants and synthesized in ref. . HR, homology-directed repair; MMR, mismatch repair–.
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Comment on

References

    1. Wang, L., Ho, A. T., Hurst, L. D. & Yang, S. Re-evaluating evidence for adaptive mutation rate variation. Nature10.1038/s41586-023-06314-y (2023). - PMC - PubMed
    1. Monroe JG, et al. Mutation bias reflects natural selection in Arabidopsis thaliana. Nature. 2022;602:101–105. doi: 10.1038/s41586-021-04269-6. - DOI - PMC - PubMed
    1. Liu H, Zhang J. Is the mutation rate lower in genomic regions of stronger selective constraints? Mol. Biol. Evol. 2022;39:msac169. doi: 10.1093/molbev/msac169. - DOI - PMC - PubMed
    1. Monroe, J. G. et al. Report of mutation biases mirroring selection in Arabidopsis thaliana unlikely to be entirely due to variant calling errors. Preprint at bioRxiv10.1101/2022.08.21.504682 (2022).
    1. Belfield EJ, et al. DNA mismatch repair preferentially protects genes from mutation. Genome Res. 2018;28:66–74. doi: 10.1101/gr.219303.116. - DOI - PMC - PubMed