Selection promotes age-dependent degeneration of the mitochondrial genome.

ABSTRACT: Somatic mutations in mitochondrial genomes (mtDNA) accumulate exponentially during aging. Using single cell sequencing, we characterize the spectrum of age-accumulated mtDNA mutations in mouse and human liver and identify directional forces that accelerate the accumulation of mutations beyond the rate predicted by a neutral model. "Driver" mutations that give genomes a replicative advantage rose to high cellular abundance and carried along "passenger" mutations, some of which are deleterious. In addition, alleles that alter mtDNA-encoded proteins selectively increased in abundance overtime, strongly supporting the idea of a "destructive" selection that favors genomes lacking function. Overall, this combination of selective forces acting in hepatocytes promotes somatic accumulation of mutat

SUBMITTER: Korotkevich E 

PROVIDER: S-EPMC11463671 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature