Genome-wide analysis of mutations in mutant lineages selected following fast-neutron irradiation mutagenesis of Arabidopsis thaliana
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AbstractIonizing radiation has long been known to induce heritable mutagenic change in DNA sequence. However, the genome-wide effect of radiation is not well understood. Here we report the molecular properties and frequency of mutations in phenotypically selected mutant lines isolated following exposure of the genetic model flowering plant Arabidopsis thaliana to fast neutrons (FNs). Previous studies suggested that FNs predominantly induce deletions longer than a kilobase in A. thaliana. However, we found a higher frequency of single base substitution than deletion mutations. While the overall frequency and molecular spectrum of fast-neutron (FN)-induced single base substitutions differed substantially from those of "background" mutations arising spontaneously in laboratory-grown plants, G:C>A:T transitions were favored in both. We found that FN-induced G:C>A:T transitions were concentrated at pyrimidine dinucleotide sites, suggesting that FNs promote the formation of mutational covalent linkages between adjacent pyrimidine residues. In addition, we found that FNs induced more single base than large deletions, and that these single base deletions were possibly caused by replication slippage. Our observations provide an initial picture of the genome-wide molecular profile of mutations induced in A. thaliana by FN irradiation and are particularly informative of the nature and extent of genome-wide mutation in lines selected on the basis of mutant phenotypes from FN-mutagenized A. thaliana populations.
CitationBelfield EJ, Gan X, Mithani A, Brown C, Jiang C, et al. (2012) Genome-wide analysis of mutations in mutant lineages selected following fast-neutron irradiation mutagenesis of Arabidopsis thaliana. Genome Research 22: 1306-1315. doi:10.1101/gr.131474.111.
PublisherCold Spring Harbor Laboratory Press
PubMed Central IDPMC3396371
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- The rate and molecular spectrum of spontaneous mutations in Arabidopsis thaliana.
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- Issue date: 2010 Jan 1
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- Issue date: 2017
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- Issue date: 2015 Apr
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- Issue date: 2014 Nov
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- Authors: O'Neill CM, Baker D, Bennett G, Clarke J, Bancroft I
- Issue date: 2011 Dec
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