Molecular Clocks Are Time-Dependent

If you’re a regular reader of Dienekes blog, you’d know he’s consistently raised concerns that calibrations of molecular clocks don’t quite fit the bill. Yesterday, he posted an addendum and shared a new paper in which authors advocate that molecular clock can be calibrated upon an archaeological context (not phylogeny-based) and human mtDNA estimates of dates of population and phylogenetic events should be adjusted to time-dependent mutation rate estimates.

I’m not gonna get into a rehashing of Dienekes’ post, I wouldn’t do as good of a job even if I did… but you should jump on over and read what he has to say and how he explains his criticisms of how the clock has been calibrated in the past. I want to spend some time in this post discussing some of the results of the paper he shared, “Characterizing the Time-Dependency of Human Mitochondrial DNA Mutation Rate Estimates,” in Molecular Biology and Evolution. The authors sought to establish genealogy-based estimates of the mtDNA mutation rate using both hypervariable and coding region data, they also wanted to figure out if multiple hits  affect the discrepancy between the different methods of mutation rate estimation.

So they setup new genealogy-based rates from 2,500 to 50,000 years ago using mtDNA from populations in the Canary Islands, Polynesia, Micronesia, North America, Taiwan, Indonesia, and Oceania. The populations were selected based upon relative isolation and the  available archaeological dates for the time of first human arrival, haplotypic data from neighboring regions, and indigenous haplotypes for that region.

The authors were able to calculate that the evolutionary mutation rate between approximately 2,500 and 50,000 years ago was much different than that from 50,000 to 6 million years ago. They suggest that since earlier mutation rates, ones based upon pedigrees, are not affected by the processes of
bottlenecks and selection, except for purifying selection on lethal alleles, they can’t weed out the effects demographic processes. Using their time-dependent approach they observe that molecular clock was accelerated for large Neolithic populations and is similar to the pedigree rate, but for the smaller Paleolithic hunter-gatherers it was much lower…. makes sense, as populations grow, variability accelerates.

    B. M. Henn, C. R. Gignoux, M. W. Feldman, J. L. Mountain (2008). Characterizing the Time-Dependency of Human Mitochondrial DNA Mutation Rate Estimates Molecular Biology and Evolution DOI: 10.1093/molbev/msn244

3 thoughts on “Molecular Clocks Are Time-Dependent

  1. Yeah, I remember discussing it with Feldman and Zhivotovsky in 2003 or 2004 when their data clearly showed two temporal layers of population processes, with Africa showing more activity in the more recent stratum, while America, Australia and parts of Eurasia in the older stratum. Maybe this paper will convince some of the nay-sayers that low allele diversity in America and high diversity in Africa is a matter of demography and population size and not a direct reflection of age. A good sequel to this paper would be the one revising the existing phylogenies to reflect “back migrations” into Africa caused by population expansions at 20,000, 10,000 and 5,000 years ago. Y chromosome’s YAP+ haplotypes is the first candidate that comes to mind. At the same time, America and Australasia remained isolated and didn’t experience population growth and gene flow of Old World magnitude.

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