title: No recombination of mtDNA after heteroplasmy for 50 generations in the mouse maternal germline.
abstract: Variants of mitochondrial DNA (mtDNA) are commonly used as markers to track human evolution because of the high sequence divergence and exclusive maternal inheritance. It is assumed that the inheritance is clonal, i.e. that mtDNA is transmitted between generations without germline recombination. In contrast to this assumption, a number of studies have reported the presence of recombinant mtDNA molecules in cell lines and animal tissues, including humans. If germline recombination of mtDNA is frequent, it would strongly impact phylogenetic and population studies by altering estimates of coalescent time and branch lengths in phylogenetic trees. Unfortunately, this whole area is controversial and the experimental approaches have been widely criticized as they often depend on polymerase chain reaction (PCR) amplification of mtDNA and/or involve studies of transformed cell lines. In this study, we used an in vivo mouse model that has had germline heteroplasmy for a defined set of mtDNA mutations for more than 50 generations. To assess recombination, we adapted and validated a method based on cloning of single mtDNA molecules in the λ phage, without prior PCR amplification, followed by subsequent mutation analysis. We screened 2922 mtDNA molecules and found no germline recombination after transmission of mtDNA under genetically and evolutionary relevant conditions in mammals.
authors.affiliation: Department of Laboratory Medicine, Karolinska Institutet, S-17177 Stockholm, Sweden, Research Programs Unit - Molecular Neurology, Biomedicum Helsinki, University of Helsinki, 00290 Finland and Max Planck Institute for Biology of Ageing, D-50931 Cologne, Germany.
authors.forename: Erik
authors.initials: E
authors.lastname: Hagström
authors.forename: Christoph
authors.initials: C
authors.lastname: Freyer
authors.forename: Brendan J
authors.initials: BJ
authors.lastname: Battersby
authors.forename: James B
authors.initials: JB
authors.lastname: Stewart
authors.forename: Nils-Göran
authors.initials: NG
authors.lastname: Larsson
mesh_terms: D000818:Animals; D016477:Artifacts; D010582:Bacteriophage lambda / Q000235:genetics; D003001:Cloning, Molecular; D004272:DNA, Mitochondrial / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D016133:Polymerase Chain Reaction; D011995:Recombination, Genetic
chemical_list: D004272:DNA, Mitochondrial