Characterizing the time dependency of human mitochondrial DNA mutation rate estimates

Area of Science:

• Evolutionary Biology
• Genetics
• Population Genetics

Background:

• A significant discrepancy exists between pedigree-based and phylogeny-based estimates of mitochondrial DNA (mtDNA) mutation rates.
• Previous studies, particularly human-chimpanzee comparisons, have yielded higher mutation rate estimates than those derived from human pedigrees.

Purpose of the Study:

• To characterize the time dependency of the human mitochondrial hypervariable region one (HVR1) mutation rate.
• To reconcile the discrepancy between different methods of estimating mtDNA mutation rates.

Main Methods:

• Generated 14 new phylogeny-based mutation rate estimates using within-human comparisons and archaeological dates.
• Analyzed both mtDNA control region (HVR1) and coding region mutation rates.
• Explored the role of multiple nucleotide hits in explaining rate discrepancies.

Main Results:

• Phylogeny-based estimates using within-human comparisons (15,000–50,000 years ago) were 2-fold lower than pedigree-based estimates.
• A rapid decay in human mtDNA mutation rate was observed between approximately 2,500 and 50,000 years ago.
• Multiple hits may explain human-chimpanzee discrepancies but not the rapid decline in within-human rate estimates.

Conclusions:

• Human mtDNA mutation rates exhibit significant time dependency, with a rapid decay in recent evolutionary history.
• Demographic processes, like serial bottlenecks, likely explain the observed rate differences.
• Existing estimates of human population and phylogenetic events based on mtDNA may require adjustment.