Purifying selection against pathogenic mitochondrial DNA in human T cells


  • M.A. Walker
  • C.A. Lareau
  • L.S. Ludwig
  • A. Karaa
  • V.G. Sankaran
  • A. Regev
  • V.K. Mootha


  • New England Journal of Medicine


  • N Engl J Med 383 (16): 1556-1563


  • 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.