Purifying Selection against Pathogenic Mitochondrial DNA in Human T Cells

N Engl J Med. 2020 Oct 15;383(16):1556-1563. doi: 10.1056/NEJMoa2001265. Epub 2020 Aug 12.


Many mitochondrial diseases are caused by mutations in mitochondrial DNA (mtDNA). Patients' cells contain a mixture of mutant and nonmutant mtDNA (a phenomenon called heteroplasmy). The proportion of mutant mtDNA varies across patients and among tissues within a patient. We simultaneously assayed single-cell heteroplasmy and cell state in thousands of blood cells obtained from three unrelated patients who had A3243G-associated mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes. We observed a broad range of heteroplasmy across all cell types but also found markedly reduced heteroplasmy in T cells, a finding consistent with purifying selection within this lineage. We observed this pattern in six additional patients who had heteroplasmic A3243G without strokelike episodes. (Funded by the Marriott Foundation and others.).

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • DNA, Mitochondrial / genetics*
  • Genome, Mitochondrial
  • Humans
  • Leukocytes, Mononuclear
  • MELAS Syndrome / genetics
  • Male
  • Middle Aged
  • Mutation*
  • Polymorphism, Genetic*
  • T-Lymphocytes*


  • DNA, Mitochondrial