Effect of collapsed duplications on diversity estimates: what to expect

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• dc.contributor.author Hartasánchez Frenk, Diego Andrés, 1982-
• dc.contributor.author Brasó-Vives, Marina, 1990-
• dc.contributor.author Heredia Genestar, José María, 1985-
• dc.contributor.author Pybus Oliveras, Marc, 1985-
• dc.contributor.author Navarro i Cuartiellas, Arcadi, 1969-
• dc.date.accessioned 2019-11-20T08:48:31Z
• dc.date.available 2019-11-20T08:48:31Z
• dc.date.issued 2018
• dc.description.abstract The study of segmental duplications (SDs) and copy-number variants (CNVs) is of great importance in the fields of genomics and evolution. However, SDs and CNVs are usually excluded from genome-wide scans for natural selection. Because of high identity between copies, SDs and CNVs that are not included in reference genomes are prone to be collapsed-that is, mistakenly aligned to the same region-when aligning sequence data from single individuals to the reference. Such collapsed duplications are additionally challenging because concerted evolution between duplications alters their site frequency spectrum and linkage disequilibrium patterns. To investigate the potential effect of collapsed duplications upon natural selection scans we obtained expectations for four summary statistics from simulations of duplications evolving under a range of interlocus gene conversion and crossover rates. We confirm that summary statistics traditionally used to detect the action of natural selection on DNA sequences cannot be applied to SDs and CNVs since in some cases values for known duplications mimic selective signatures. As a proof of concept of the pervasiveness of collapsed duplications, we analyzed data from the 1,000 Genomes Project. We find that, within regions identified as variable in copy number, diversity between individuals with the duplication is consistently higher than between individuals without the duplication. Furthermore, the frequency of single nucleotide variants (SNVs) deviating from Hardy-Weinberg Equilibrium is higher in individuals with the duplication, which strongly suggests that higher diversity is a consequence of collapsed duplications and incorrect evaluation of SNVs within these CNV regions.
• dc.description.sponsorship This work has been supported by Ministerio de Ciencia e Innovación, Spain (BFU2015-68649-P, MINECO/FEDER, UE), the Direcció General de Recerca, Generalitat de Catalunya (2014SGR1311 and 2014SGR866), the Spanish National Institute of Bioinformatics (PT13/0001/0026) of the Instituto de Salud Carlos III, grant MDM-2014-0370 through the “María de Maeztu” Programme for Units of Excellence in R&D to UPF’s Department of Experimental and Health Sciences; a grant to D.A.H. from Conacyt; and by the Fondo Europeo de Desarrollo Regional (FEDER) and the Fondo Social Europeo (FSE).
• dc.format.mimetype application/pdf
• dc.identifier.citation Hartasánchez DA, Brasó-Vives M, Heredia-Genestar JM, Pybus M, Navarro A. Effect of collapsed duplications on diversity estimates: what to expect. Genome Biol Evol. 2018; 10(11):2899-2905. DOI 10.1093/gbe/evy223
• dc.identifier.doi http://dx.doi.org/10.1093/gbe/evy223
• dc.identifier.issn 1759-6653
• dc.identifier.uri http://hdl.handle.net/10230/42904
• dc.language.iso eng
• dc.publisher Oxford University Press
• dc.relation.ispartof Genome Biol Evol. 2018; 10(11):2899-2905
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2015-68649-P
• dc.rights © The Author(s) 2018. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Copy number variation
• dc.subject.keyword Neutrality statistics
• dc.subject.keyword Interlocus gene conversion
• dc.title Effect of collapsed duplications on diversity estimates: what to expect
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion