Site-specific selection reveals selective constraints and functionality of tumor somatic mtDNA mutations.

ABSTRACT:

Background

Previous studies have indicated that tumor mitochondrial DNA (mtDNA) mutations are primarily shaped by relaxed negative selection, which is contradictory to the critical roles of mtDNA mutations in tumorigenesis. Therefore, we hypothesized that site-specific selection may influence tumor mtDNA mutations.

Methods

To test our hypothesis, we developed the largest collection of tumor mtDNA mutations to date and evaluated how natural selection shaped mtDNA mutation patterns.

Results

Our data demonstrated that both positive and negative selections acted on specific positions or functional units of tumor mtDNAs, although the landscape of these mutations was consistent with the relaxation of negative selection. In particular, mutation rate (mutation number in a reg

SUBMITTER: Li D 

PROVIDER: S-EPMC5704541 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature