Mitochondrial haplotype and mito-nuclear matching drive somatic mutation and selection throughout aging.

ABSTRACT: Mitochondrial genomes co-evolve with the nuclear genome over evolutionary timescales and are shaped by selection in the female germline. Here, we investigate how mismatching between nuclear and mitochondrial ancestry impacts the somatic evolution of the mt-genome in different tissues throughout aging. We used ultra-sensitive Duplex Sequencing to profile ~2.5 million mt-genomes across five mitochondrial haplotypes and three tissues in young and aged mice, cataloging ~1.2 million mitochondrial somatic and ultra low frequency inherited mutations, of which 81,097 are unique. We identify haplotype-specific mutational patterns and several mutational hotspots, including at the Light Strand Origin of Replication, which consistently exhibits the highest mutation frequency. We show that rodents exhi

SUBMITTER: Serrano IM 

PROVIDER: S-EPMC10028854 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature