Mitochondrial DNA mosaicism in normal human somatic cells.

ABSTRACT: Somatic cells accumulate genomic alterations with age; however, our understanding of mitochondrial DNA (mtDNA) mosaicism remains limited. Here we investigated the genomes of 2,096 clones derived from three cell types across 31 donors, identifying 6,451 mtDNA variants with heteroplasmy levels of ≳0.3%. While the majority of these variants were unique to individual clones, suggesting stochastic acquisition with age, 409 variants (6%) were shared across multiple embryonic lineages, indicating their origin from heteroplasmy in fertilized eggs. The mutational spectrum exhibited replication-strand bias, implicating mtDNA replication as a major mutational process. We evaluated the mtDNA mutation rate (5.0 × 10^-8 per base pair) and a turnover frequency of 10-20 per year, which are funda

SUBMITTER: An J 

PROVIDER: S-EPMC11319206 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature