Mammalian mitochondrial DNA (mtDNA) is inherited principally down the maternal line, but the mechanisms involved are not fully understood. Females harboring a mixture of mutant and wild-type mtDNA (heteroplasmy) transmit a varying proportion of mutant mtDNA to their offspring. In humans with mtDNA disorders, the proportion of mutated mtDNA inherited from the mother correlates with disease severity^{1, 2, 3, 4}. Rapid changes in allele frequency can occur in a single generation^{5, 6}. This could be due to a marked reduction in the number of mtDNA molecules being transmitted from mother to offspring (the mitochondrial genetic bottleneck), to the partitioning of mtDNA into homoplasmic segregating units, or to the selection of a group of mtDNA molecules to re-populate the next generation. Here we show that the partitioning of mtDNA molecules into different cells before and after implantation, followed by the segregation of replicating mtDNA between proliferating primordial germ cells, is responsible for the different levels of heteroplasmy seen in the offspring of heteroplasmic female mice.

1. Mitochondrial Research Group, Newcastle University, Newcastle NE2 4HH, UK.
2. Virginia Bioinformatics Institute, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061, USA.
3. Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
4. Division of Biology, City of Hope, 1500 E. Duarte Rd., Duarte, California 91010, USA.
5. The Murdoch Children's Research Institute & Department of Paediatrics (University of Melbourne), Royal Children's Hospital, Parkville, Melbourne, Victoria 3052, Australia.
6. Institute of Human Genetics, Newcastle University, Newcastle NE2 4HH, UK.
7. Present address: Department of Zoology, The University of Melbourne, Victoria 3010, Australia.

Correspondence to: Patrick F Chinnery^1,6 e-mail: p.f.chinnery@ncl.ac.uk

MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated.

NPG Journals

by Subject Area

• Chemistry

  • Chemistry
  • Drug discovery
  • Biotechnology
  • Materials
  • Methods & Protocols

• Clinical Practice & Research

  • Cancer
  • Cardiovascular medicine
  • Dentistry
  • Endocrinology
  • Gastroenterology & Hepatology
  • Methods & Protocols
  • Pathology & Pathobiology
  • Urology

• Earth & Environment

  • Earth sciences
  • Evolution & Ecology

• Life sciences

  • Biotechnology
  • Cancer
  • Development
  • Drug discovery
  • Evolution & Ecology
  • Genetics
  • Immunology
  • Medical research
  • Methods & Protocols
  • Microbiology
  • Molecular cell biology
  • Neuroscience
  • Pharmacology
  • Systems biology

• Physical sciences

  • Physics
  • Materials

by A - Z Index