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• W3135444016 startingPage "e1009221" @default.
• W3135444016 abstract "Many complex genomic rearrangements arise through template switch errors, which occur in DNA replication when there is a transient polymerase switch to an alternate template nearby in three-dimensional space. While typically investigated at kilobase-to-megabase scales, the genomic and evolutionary consequences of this mutational process are not well characterised at smaller scales, where they are often interpreted as clusters of independent substitutions, insertions and deletions. Here we present an improved statistical approach using pair hidden Markov models, and use it to detect and describe short-range template switches underlying clusters of mutations in the multi-way alignment of hominid genomes. Using robust statistics derived from evolutionary genomic simulations, we show that template switch events have been widespread in the evolution of the great apes’ genomes and provide a parsimonious explanation for the presence of many complex mutation clusters in their phylogenetic context. Larger-scale mechanisms of genome rearrangement are typically associated with structural features around breakpoints, and accordingly we show that atypical patterns of secondary structure formation and DNA bending are present at the initial template switch loci. Our methods improve on previous non-probabilistic approaches for computational detection of template switch mutations, allowing the statistical significance of events to be assessed. By specifying realistic evolutionary parameters based on the genomes and taxa involved, our methods can be readily adapted to other intra- or inter-species comparisons." @default.
• W3135444016 created "2021-03-15" @default.
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• W3135444016 date "2021-03-02" @default.
• W3135444016 modified "2023-10-12" @default.
• W3135444016 title "Short-range template switching in great ape genomes explored using pair hidden Markov models" @default.
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• W3135444016 doi "https://doi.org/10.1371/journal.pgen.1009221" @default.
• W3135444016 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7954356" @default.
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• W3135444016 hasPublicationYear "2021" @default.
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