The mutation rate in the human mtDNA control region.

Area of Science:

• Genetics
• Human Population Genetics
• Mitochondrial DNA

Background:

• The mitochondrial DNA (mtDNA) control region mutation rate is crucial for human population history studies.
• Previous estimates of this mutation rate vary significantly, spanning two orders of magnitude.
• Direct pedigree-based assessments are essential for accurate mutation rate calibration.

Purpose of the Study:

• To re-estimate the mtDNA control region mutation rate using a large Icelandic pedigree cohort.
• To provide a more accurate calibration for human population history.
• To investigate discrepancies between pedigree-based and phylogenetic mutation rate estimates.

Main Methods:

• Sequencing of the mtDNA control region in 272 individuals from 26 Icelandic pedigrees.
• Analysis of 705 mtDNA transmission events to observe base substitutions.
• Statistical analysis to estimate mutation rates and confidence intervals.

Main Results:

• An estimated mtDNA mutation rate of 0.0043 per generation (95% CI: 0.00088-0.013) or 0.32 per site per million years (95% CI: 0.065-0.97).
• The estimated rate is intermediate compared to previous pedigree-based studies but higher than phylogenetic estimates.
• Data on insertion/deletion mutation rates, heteroplasmy, and Icelandic genealogy reliability were also obtained.

Conclusions:

• The study provides a robust, intermediate mtDNA mutation rate based on a large pedigree dataset.
• Discrepancies with phylogenetic estimates warrant further investigation into potential biases.
• Findings enhance the reliability of using Icelandic genealogy for genetic studies and population history.