Chromatin structure influences rate and spectrum of spontaneous mutations in Neurospora crassa
Abstract
Although mutation rates have been extensively studied, variation in mutation rates throughout the genome is poorly understood.
To understand patterns of genetic variation, it is important to understand how mutation rates vary. Chromatin modifications
may be an important factor in determining variation in mutation rates in eukaryotic genomes. To study variation in mutation
rates, we performed a mutation accumulation (MA) experiment in the filamentous fungus Neurospora crassa and sequenced the genomes of the 40 MA lines that had been propagated asexually for approximately 1015 
mitoses. We detected 1322 mutations in total and observed that the mutation rate was higher in regions of low GC, in domains
of H3K9 trimethylation, in centromeric regions, and in domains of H3K27 trimethylation. The rate of single-nucleotide mutations
in euchromatin was 
. In contrast, the mutation rate in H3K9me3 domains was 10-fold higher: 2.43 
. We also observed that the spectrum of single-nucleotide mutations was different between H3K9me3 and euchromatic domains.
Our statistical model of mutation rate variation predicted a moderate amount of extant genetic variation, suggesting that
the mutation rate is an important factor in determining levels of natural genetic variation. Furthermore, we characterized
mutation rates of structural variants, complex mutations, and the effect of local sequence context on the mutation rate. Our
study highlights that chromatin modifications are associated with mutation rates, and accurate evolutionary inferences should
take variation in mutation rates across the genome into account.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at https://www.genome.org/cgi/doi/10.1101/gr.276992.122.
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Freely available online through the Genome Research Open Access option.
- Received June 3, 2022.
- Accepted March 7, 2023.
This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
