Longitudinal change in mitochondrial heteroplasmy exhibits positive selection for deleterious variants.

ABSTRACT: A common feature of human aging is the acquisition of somatic mutations, and mitochondria are particularly prone to mutation due to their inefficient DNA repair and close proximity to reactive oxygen species, leading to a state of mitochondrial DNA heteroplasmy^1,2. Cross-sectional studies have demonstrated that detection of heteroplasmy increases with participant age³, a phenomenon that has been attributed to genetic drift^4-7. In this first large-scale longitudinal study, we measured heteroplasmy in two prospective cohorts (combined n=1405) at two timepoints (mean time between visits, 8.6 years), demonstrating that deleterious heteroplasmies were more likely to increase in variant allele fraction (VAF). We further demonstrated that increase in VAF was assoc

SUBMITTER: Kuiper LM 

PROVIDER: S-EPMC10996716 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature