title: MtDNA segregation in heteroplasmic tissues is common in vivo and modulated by haplotype differences and developmental stage.
abstract: The dynamics by which mitochondrial DNA (mtDNA) evolves within organisms are still poorly understood, despite the fact that inheritance and proliferation of mutated mtDNA cause fatal and incurable diseases. When two mtDNA haplotypes are present in a cell, it is usually assumed that segregation (the proliferation of one haplotype over another) is negligible. We challenge this assumption by showing that segregation depends on the genetic distance between haplotypes. We provide evidence by creating four mouse models containing mtDNA haplotype pairs of varying diversity. We find tissue-specific segregation in all models over a wide range of tissues. Key findings are segregation in postmitotic tissues (important for disease models) and segregation covering all developmental stages from prenatal to old age. We identify four dynamic regimes of mtDNA segregation. Our findings suggest potential complications for therapies in human populations: we propose "haplotype matching" as an approach to avoid these issues.
authors.affiliation: Biotechnology in Animal Production, Department for Agrobiotechnology, IFA Tulln, 3430 Tulln, Austria.|Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210 Vienna, Austria.
authors.forename: Joerg Patrick
authors.initials: JP
authors.lastname: Burgstaller
authors.affiliation: Department of Mathematics, Imperial College London, London SW7 2AZ, United Kingdom.
authors.forename: Iain G
authors.initials: IG
authors.lastname: Johnston
authors.affiliation: Department of Mathematics, Imperial College London, London SW7 2AZ, United Kingdom.
authors.forename: Nick S
authors.initials: NS
authors.lastname: Jones
authors.affiliation: Research Facility Studenec, Academy of Sciences of the Czech Republic, Květná 8, 60365 Brno, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Albrechtová
authors.affiliation: Biomodels Austria, University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210 Vienna, Austria.|Department for Agrobiotechnology, IFA Tulln, University of Natural Resources and Applied Life Sciences, Tulln 3430, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kolbe
authors.affiliation: Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210 Vienna, Austria.
authors.forename: Claus
authors.initials: C
authors.lastname: Vogl
authors.affiliation: Department of Statistics, University of Vienna, 1010 Vienna, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Futschik
authors.affiliation: Biotechnology in Animal Production, Department for Agrobiotechnology, IFA Tulln, 3430 Tulln, Austria.|Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210 Vienna, Austria.
authors.forename: Corina
authors.initials: C
authors.lastname: Mayrhofer
authors.affiliation: VetCore Facility for Research, University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210 Vienna, Austria.
authors.forename: Dieter
authors.initials: D
authors.lastname: Klein
authors.affiliation: VetCore Facility for Research, University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210 Vienna, Austria.
authors.forename: Sonja
authors.initials: S
authors.lastname: Sabitzer
authors.affiliation: VetCore Facility for Research, University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210 Vienna, Austria.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Blattner
authors.affiliation: Center for Medical Research, Medical University of Graz, 8010 Graz, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Gülly
authors.affiliation: Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Oxford OX3 9DU, United Kingdom.
authors.forename: Joanna
authors.initials: J
authors.lastname: Poulton
authors.affiliation: Institute of Laboratory Animal Science, University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210 Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rülicke
authors.affiliation: Research Facility Studenec, Academy of Sciences of the Czech Republic, Květná 8, 60365 Brno, Czech Republic.
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Piálek
authors.affiliation: VetCore Facility for Research, University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210 Vienna, Austria.
authors.forename: Ralf
authors.initials: R
authors.lastname: Steinborn
authors.affiliation: Biotechnology in Animal Production, Department for Agrobiotechnology, IFA Tulln, 3430 Tulln, Austria.|Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210 Vienna, Austria.
authors.forename: Gottfried
authors.initials: G
authors.lastname: Brem
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004272:DNA, Mitochondrial / Q000235:genetics*; D004195:Disease Models, Animal; D006239:Haplotypes; D006801:Humans; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data
chemical_list: D004272:DNA, Mitochondrial