文章基本信息

标题：Substitutions of short heterologous DNA segments of intragenomic or extragenomic origins produce clustered genomic polymorphisms
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作者：Klaus Harms ; Asbjørn Lunnan ; Nils Hülter 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2016
卷号：113
期号：52
页码：15066-15071
DOI：10.1073/pnas.1615819114
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceClustered genomic polymorphisms in DNA, such as microindels and stretches of nucleotide changes, play an important role in genome evolution. Here, we report a mutation mechanism responsible for such genomic polymorphisms where short, single-stranded DNA molecules invade double-stranded DNA and replace short genomic segments. We show, in a bacterial model organism, that the genomic replacements occur with very low levels of sequence identity (microhomologies). The invading DNA can be of intagenomic or foreign origin. Genotoxic stress, horizontally taken-up DNA, or lack of genome maintenance functions increase the mutation frequency up to 7,000-fold. Bioinformatic approaches suggest that this class of mutations is widespread in prokaryotes and eukaryotes and may have a role in tumorigenesis. In a screen for unexplained mutation events we identified a previously unrecognized mechanism generating clustered DNA polymorphisms such as microindels and cumulative SNPs. The mechanism, short-patch double illegitimate recombination (SPDIR), facilitates short single-stranded DNA molecules to invade and replace genomic DNA through two joint illegitimate recombination events. SPDIR is controlled by key components of the cellular genome maintenance machinery in the gram-negative bacterium Acinetobacter baylyi. The source DNA is primarily intragenomic but can also be acquired through horizontal gene transfer. The DNA replacements are nonreciprocal and locus independent. Bioinformatic approaches reveal occurrence of SPDIR events in the gram-positive human pathogen Streptococcus pneumoniae and in the human genome.
关键词：illegitimate recombination ; mutation ; microindels