Germline de novo mutation rates on exons versus introns in humans
Rodriguez-Galindo, Miguel (Centre de Regulació Genòmica)
Casillas Viladerrams, Sònia (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Weghorn, Donate (Universitat Pompeu Fabra)
Barbadilla Prados, Antonio (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")

Date:	2020
Abstract:	A main assumption of molecular population genetics is that genomic mutation rate does not depend on sequence function. Challenging this assumption, a recent study has found a reduction in the mutation rate in exons compared to introns in somatic cells, ascribed to an enhanced exonic mismatch repair system activity. If this reduction happens also in the germline, it can compromise studies of population genomics, including the detection of selection when using introns as proxies for neutrality. Here we compile and analyze published germline de novo mutation data to test if the exonic mutation rate is also reduced in germ cells. After controlling for sampling bias in datasets with diseased probands and extended nucleotide context dependency, we find no reduction in the mutation rate in exons compared to introns in the germline. Therefore, there is no evidence that enhanced exonic mismatch repair activity determines the mutation rate in germline cells. Evidence that somatic mutation rates in introns exceed those in exons challenges the molecular evolution tenet that mutation rate and sequence function are independent. Here, authors analyze germline de novo mutations and reveal no evidence for mutation rate differences between exons and introns.
Grants:	Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-1379 Agencia Estatal de Investigación CGL2017-89160P
Note:	Altres ajuts: Fundació La Caixa: LCF/BQ/DR19/11740019
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Computational models ; Molecular evolution ; Genetic variation ; Mutagenesis
Published in:	Nature communications, Vol. 11 (July 2020) , art. 3304, ISSN 2041-1723

DOI: 10.1038/s41467-020-17162-z
PMID: 32620809

9 p, 1.4 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Biotecnologia i de Biomedicina (IBB)
Articles > Research articles
Articles > Published articles