Large-scale genetic analysis reveals mammalian mtDNA heteroplasmy dynamics and variance increase through lifetimes and generations

Joerg P. Burgstaller (), Thomas Kolbe, Vitezslav Havlicek, Stephanie Hembach, Joanna Poulton, Jaroslav Piálek, Ralf Steinborn, Thomas Rülicke, Gottfried Brem, Nick S. Jones () and Iain G. Johnston ()
Additional contact information
Joerg P. Burgstaller: Biotechnology in Animal Production
Thomas Kolbe: Biomodels Austria, University of Veterinary Medicine Vienna
Vitezslav Havlicek: University of Veterinary Medicine
Stephanie Hembach: Biotechnology in Animal Production
Joanna Poulton: University of Oxford
Jaroslav Piálek: Institute of Vertebrate Biology of the Czech Academy of Sciences
Ralf Steinborn: University of Veterinary Medicine Vienna
Thomas Rülicke: University of Veterinary Medicine Vienna
Gottfried Brem: Biotechnology in Animal Production
Nick S. Jones: Imperial College London
Iain G. Johnston: University of Birmingham

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: Abstract Vital mitochondrial DNA (mtDNA) populations exist in cells and may consist of heteroplasmic mixtures of mtDNA types. The evolution of these heteroplasmic populations through development, ageing, and generations is central to genetic diseases, but is poorly understood in mammals. Here we dissect these population dynamics using a dataset of unprecedented size and temporal span, comprising 1947 single-cell oocyte and 899 somatic measurements of heteroplasmy change throughout lifetimes and generations in two genetically distinct mouse models. We provide a novel and detailed quantitative characterisation of the linear increase in heteroplasmy variance throughout mammalian life courses in oocytes and pups. We find that differences in mean heteroplasmy are induced between generations, and the heteroplasmy of germline and somatic precursors diverge early in development, with a haplotype-specific direction of segregation. We develop stochastic theory predicting the implications of these dynamics for ageing and disease manifestation and discuss its application to human mtDNA dynamics.

Date: 2018
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-018-04797-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04797-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-04797-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().