Correcting for purifying selection: an improved human mitochondrial molecular clock.

Area of Science:

• Genetics
• Evolutionary Biology
• Anthropology

Background:

• Existing molecular clocks for human mitochondrial DNA (mtDNA) are limited, often excluding the control region or using problematic linear models.
• Purifying selection has a modest effect on the mtDNA coding region, necessitating a refined calibration approach.

Purpose of the Study:

• To develop an improved molecular clock for dating human mtDNA by incorporating the entire genome.
• To establish a time-dependent mutation rate for human mtDNA, validated against independent evidence.
• To provide new estimates for human migration timings, particularly the Out-of-Africa dispersal and settlement of the Americas.

Main Methods:

• Construction of a worldwide phylogeny using over 2000 complete human mtDNA genomes.
• Calibration of the molecular clock against the human-chimpanzee divergence time.
• Validation of the corrected mutation rate using archaeological data from the Canary Islands, Remote Oceania, Europe, and the Americas.

Main Results:

• A novel, time-dependent mutation rate for the entire human mtDNA genome was established.
• The corrected clock aligns archaeological and genetic data for the settlement of the Americas around 15,000 years ago.
• The Out-of-Africa dispersal is dated to 55-70 kya, preceding current archaeological records.

Conclusions:

• The improved molecular clock offers more accurate dating for human mtDNA evolution and migration.
• The findings highlight a temporal gap between genetic evidence for early human dispersal and archaeological findings.
• New estimates for mtDNA control region mutation rates and positional mutation rates were provided, crucial for phylogenetic analyses.