Clonally expanded mtDNA point mutations are abundant in individual cells of human tissues

Ekaterina Nekhaeva, Natalya D. Bodyak, Yevgenya Kraytsberg, Sean B. McGrath, Nathalie J. Van Orsouw, Anna Pluzhnikov, Jeanne Y. Wei, Jan Vijg, Konstantin Khrapko

Research output: Contribution to journalArticlepeer-review

160 Scopus citations


Using single-cell sequence analysis, we discovered that a high proportion of cells in tissues as diverse as buccal epithelium and heart muscle contain high proportions of clonal mutant mtDNA expanded from single initial mutant mtDNA molecules. We demonstrate that intracellular clonal expansion of somatic point mutations is a common event in normal human tissues. This finding implies efficient homogenization of mitochondrial genomes within individual cells. Significant qualitative differences observed between the spectra of clonally expanded mutations in proliferating epithelial cells and postmitotic cardiomyocytes suggest, however, that either the processes generating these mutations or mechanisms driving them to homoplasmy are likely to be fundamentally different between the two tissues. Furthermore, the ability of somatic mtDNA mutations to expand (required for their phenotypic expression), as well as their apparently high incidence, reinforces the possibility that these mutations may be involved actively in various physiological processes such as aging and degenerative disease. The abundance of clonally expanded point mutations in individual cells of normal tissues also suggests that the recently discovered accumulation of mtDNA mutations in tumors may be explained by processes that are similar or identical to those operating in the normal tissue.

Original languageEnglish (US)
Pages (from-to)5521-5526
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number8
StatePublished - Apr 16 2002
Externally publishedYes


  • Aging
  • Cancer
  • Clonal expansion
  • Single cell
  • Somatic mutation

ASJC Scopus subject areas

  • General


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