Purifying selection against pathogenic mitochondrial DNA in human T cells
Authors
- M.A. Walker
- C.A. Lareau
- L.S. Ludwig
- A. Karaa
- V.G. Sankaran
- A. Regev
- V.K. Mootha
Journal
- New England Journal of Medicine
Citation
- N Engl J Med 383 (16): 1556-1563
Abstract
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.