A1 Journal article (refereed)
Chromatin structure influences rate and spectrum of spontaneous mutations in Neurospora crassa (2023)

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

JYU authors or editors

Publication details

All authors or editors: Villalba de la Peña, Mariana; Summanen, Pauliina A. M.; Liukkonen, Martta; Kronholm, Ilkka

Journal or series: Genome Research

ISSN: 1088-9051

eISSN: 1549-5469

Publication year: 2023

Publication date: 15/03/2023

Volume: 33

Issue number: 4

Pages range: 599-611

Publisher: Cold Spring Harbor Laboratory

Publication country: United States

Publication language: English

DOI: https://doi.org/10.1101/gr.276992.122

Publication open access: Openly available

Publication channel open access: Partially open access channel

Publication is parallel published (JYX): https://jyx.jyu.fi/handle/123456789/87189

Web address of parallel published publication (pre-print): https://www.biorxiv.org/content/10.1101/2022.03.13.484164v4

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.

Keywords: epigenetics; genomics; fungi; genetics; genome; mutations

Free keywords: fungi; mutation accumulation; genomics; epigenetics; H3K9 trimethylation; H3K27 trimethylation

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Ministry reporting: Yes

Reporting Year: 2023

Preliminary JUFO rating: 3