High mitochondrial mutation rates estimated from deep-rooting Costa Rican pedigrees

Area of Science:

• Genetics
• Evolutionary Biology
• Population Genetics

Background:

• Mutation rate estimates for mitochondrial DNA hypervariable Region I (HVR-I) vary significantly.
• Previous pedigree-based studies were limited to European populations.
• Phylogenetic and pedigree-based mutation rate estimations often yield discrepant results.

Purpose of the Study:

• To investigate mitochondrial DNA HVR-I mutation rates in a mixed-origin population using deep-rooting pedigrees.
• To compare direct pedigree-based mutation rate estimates with those derived from phylogenetic analyses.
• To assess the impact of mutational hotspots and potential genealogical errors on mutation rate calculations.

Main Methods:

• Analysis of 19 deep-rooting pedigrees from a mixed-origin population in Costa Rica.
• Calculation of HVR-I mutation rates considering all mutations.
• Refined mutation rate calculation excluding mutational hotspots and potentially erroneous genealogical branches.

Main Results:

• A high HVR-I mutation rate of 1.24 × 10⁻⁶ per site per year was observed.
• This direct pedigree-based rate is at least threefold higher than estimates from phylogenies.
• Pedigree mutation rates are substantially higher than those predicted by neutral evolution models.

Conclusions:

• Direct pedigree studies reveal significantly higher mitochondrial DNA HVR-I mutation rates than phylogenetic methods.
• Discrepancies between mutation rate estimation methods persist and require further investigation.
• Both high direct estimates and lower phylogenetic estimates should inform evolutionary and demographic modeling.