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The rate and spectrum of somatic mutations can diverge from that of germline mutations. This is because somatic tissues experience different mutagenic processes than germline tissues. Here, we use nanorate sequencing (NanoSeq) to identify somatic mutations in Arabidopsis shoots with high sensitivity. We report a somatic mutation rate of 3.6x10^-8 mutations/bp, ~4-5x the germline mutation rate. Somatic mutations displayed elevated signatures consistent with oxidative damage, UV damage, and transcription-coupled nucleotide excision repair. Both somatic and germline mutations were enriched in transposable elements and depleted in genes, but this depletion was greater in germline mutations. Somatic mutation rate correlated with proximity to the centromere, DNA methylation, chromatin accessibility, and gene/TE content, properties which were also largely true of germline mutations. We note DNA methylation and chromatin accessibility have different predicted effects on mutation rate for genic and non-genic regions; DNA methylation associates with a greater increase in mutation rate when in non-genic regions, and accessible chromatin associates with a lower mutation rate in non-genic regions but a higher mutation rate in genic regions. Together, these results characterize key differences and similarities in the genomic distribution of somatic and germline mutations.
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Genome-wide analysis of cadmium-induced, germline mutations in a long-term Daphnia pulex mutation-accumulation experiment over 1,123 generations.
Germline mutations provide the raw material for all evolutionary processes and contribute to the occurrence of spontaneous human diseases and disorders. Yet despite the daily interaction of humans and other organisms with an increasing number of chemicals that are potentially mutagenic, precise measurements of chemically induced changes to the genome-wide rate and spectrum of germline mutation are lacking. A large-scale mutation-accumulation experiment was propagated in the presence and absence of an environmentally relevant cadmium concentration to quantify the influence of cadmium on germline mutation rates and spectra. Cadmium exposure dramatically changed the genome-wide rates and regional spectra of germline mutations. In comparison with those in control conditions, exposed to cadmium had a higher overall mutation rates and a lower overall mutation rate. exposed to cadmium had a higher intergenic mutation rate and a lower exonic mutation rate. The higher intergenic mutation rate under cadmium exposure was the result of an elevated intergenic rate, whereas the lower exon mutation rate in cadmium was the result of a complete loss of exonic mutations-mutations that are known to be enriched at 5-hydroxymethylcytosine. We experimentally show that cadmium exposure significantly reduced 5-hydroxymethylcytosine levels. These results provide evidence that cadmium changes regional mutation rates and can influence regional rates by interfering with an epigenetic process in the germline. We further suggest these observed cadmium-induced changes to the germline mutation rate may be explained by cadmium's inhibition of zinc-containing domains. The cadmium-induced changes to germline mutation rates and spectra we report provide a comprehensive view of the mutagenic perils of cadmium and give insight into its potential impact on human population health. https://doi.org/10.1289/EHP8932.
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- Award ID(s):
- 1922914
- PAR ID:
- 10382885
- Date Published:
- Journal Name:
- Environmental health perspectives
- Volume:
- 129
- Issue:
- 10
- ISSN:
- 0091-6765
- Page Range / eLocation ID:
- 107003
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Agashe, Deepa (Ed.)Abstract The rate at which mutations arise is a fundamental parameter of biology. Despite progress in measuring germline mutation rates across diverse taxa, such estimates are missing for much of Earth's biodiversity. Here, we present the first estimate of a germline mutation rate from the phylum Mollusca. We sequenced three pedigreed families of the white abalone Haliotis sorenseni, a long-lived, large-bodied, and critically endangered mollusk, and estimated a de novo mutation rate of 8.60 × 10−9 single nucleotide mutations per site per generation. This mutation rate is similar to rates measured in vertebrates with comparable generation times and longevity to abalone, and higher than mutation rates measured in faster-reproducing invertebrates. The spectrum of de novo mutations is also similar to that seen in vertebrate species, although an excess of rare C > A polymorphisms in wild individuals suggests that a modifier allele or environmental exposure may have once increased C > A mutation rates. We use our rate to infer baseline effective population sizes (Ne) across multiple Pacific abalone and find that abalone persisted over most of their evolutionary history as large and stable populations, in contrast to extreme fluctuations over recent history and small census sizes in the present day. We then use our mutation rate to infer the timing and pattern of evolution of the abalone genus Haliotis, which was previously unknown due to few fossil calibrations. Our findings are an important step toward understanding mutation rate evolution and they establish a key parameter for conservation and evolutionary genomics research in mollusks.more » « less
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