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Publication type: Journal Article
Document type: Full Paper

Year: 2014

Author(s): Burgstaller, JP; Johnston, IG; Jones, NS; Albrechtová, J; Kolbe, T; Vogl, C; Futschik, A; Mayrhofer, C; Klein, D; Sabitzer, S; Blattner, M; Gülly, C; Poulton, J; Rülicke, T; Piálek, J; Steinborn, R; Brem, G

Title: MtDNA segregation in heteroplasmic tissues is common in vivo and modulated by haplotype differences and developmental stage.

Source: Cell Rep. 2014; 7(6):2031-2041



Authors Vetmeduni Vienna:

Brem Gottfried
Burgstaller Jörg
Itze-Mayrhofer Corina
Klein Dieter
Kolbe Thomas
Rülicke Thomas
Steinborn Ralf
Vogl Claus
Weigelsperger Sonja

Vetmed Research Units
Biomodels Austria
Institute of Laboratory Animal Science
Institute of Animal Breeding and Genetics, Unit of Molecular Genetics
Institute of Animal Breeding and Genetics, Unit of Reproductive Biology
VetCore


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.

Keywords Pubmed: Amino Acid Sequence
Animals
DNA, Mitochondrial/genetics*
Disease Models, Animal
Haplotypes
Humans
Mice
Models, Genetic
Molecular Sequence Data


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