Chromatin structure influences rate and spectrum of spontaneous mutations in Neurospora crassa

Abstract
While 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 experiment in the filamentous fungus Neurospora crassa, and sequenced the genomes of the 40 MA lines that had been propagated asexually for approximately 1015 [1003, 1026] 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 2.46 [2.19, 2.77] × 10-10. In contrast, the mutation rate in H3K9me3 domains was tenfold higher: 2.43 [2.25, 2.62] × 10-9. 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.
Main Authors
Format
Articles Research article
Published
2023
Series
Subjects
Publication in research information system
Publisher
Cold Spring Harbor Laboratory
The permanent address of the publication
https://urn.fi/URN:NBN:fi:jyu-202305253253Use this for linking
Review status
Peer reviewed
ISSN
1088-9051
DOI
https://doi.org/10.1101/gr.276992.122
Language
English
Published in
Genome Research
Citation
  • Villalba de la Peña, M., Summanen, P. A. M., Liukkonen, M., & Kronholm, I. (2023). Chromatin structure influences rate and spectrum of spontaneous mutations in Neurospora crassa. Genome Research, 33(4), 599-611. https://doi.org/10.1101/gr.276992.122
License
CC BY 4.0Open Access
Funder(s)
Research Council of Finland
Funding program(s)
Academy Research Fellow, AoF
Akatemiatutkija, SA
Research Council of Finland
Additional information about funding
This study was supported by a grant from the Academy of Finland (no. 321584) to IK.
Copyright© 2023 Villalba de la Peña et al.; Published by Cold Spring Harbor Laboratory Press

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