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Reconstructing past changes in locus-specific recombination rates

BACKGROUND: Recombination rates vary at the level of the species, population and individual. Now recognized as a transient feature of the genome, recombination rates at a given locus can change markedly over time. Existing inferential methods, predominantly based on linkage disequilibrium patterns,...

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Detalles Bibliográficos
Autores principales: Cox, Murray P, Holland, Barbara R, Wilkins, Matthew C, Schmid, Jan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3605148/
https://www.ncbi.nlm.nih.gov/pubmed/23442125
http://dx.doi.org/10.1186/1471-2156-14-11
Descripción
Sumario:BACKGROUND: Recombination rates vary at the level of the species, population and individual. Now recognized as a transient feature of the genome, recombination rates at a given locus can change markedly over time. Existing inferential methods, predominantly based on linkage disequilibrium patterns, return a long-term average estimate of past recombination rates. Such estimates can be misleading, but no analytical framework to infer recombination rates that have changed over time is currently available. RESULTS: We apply coalescent modeling in conjunction with a suite of summary statistics to show that the recombination history of a locus can be reconstructed from a time series of genetic samples. More usefully, we describe a new method, based on n-tuple dataset subsampling, to infer past changes in recombination rate from DNA sequences taken at a single time point. This subsampling strategy can correctly assign simulated loci to constant, increasing and decreasing recombination models with an accuracy of 84%. CONCLUSIONS: While providing an important stepping-stone to determining past recombination rates, n-tuple subsampling still exhibits a moderate error rate. Theoretical limitations indicated by coalescent theory suggest that highly accurate inference of past recombination rates will remain challenging. Nevertheless, we show for the first time that reconstructing historic recombination rates is possible in principle.