Human Mitochondrial Mutation Rates

In a May 1997 paper in Nature Genetics entitled A high observed substitution rate in the human mitochondrial DNA control region, Parsons et al. compared the rate of mitochondrial mutation observed in forensic blood analyses of humans against the commonly accepted rate derived from phylogenic studies.

If my understanding of biology is correct (I’m not a biologist), a phylogenic study is where you take two species (e.g., humans and chimpanzees), look at how different their mitochondrial RNA is (number of substitutions), look at how long ago their most recent comman ancestor (MRCA) lived, and calculate the substitution rate in substitutions per site per year. According to the article (they reference 6 sources), phylogenic studies give a rate of about 0.025-0.260 substitutions/site/Myear. Assuming a generation time of 20 years, this corresponds to one mutation every 600 generations, and a MRCA of the human race around 133,000 years ago.

In this study, the authors did an analysis on four sources:

• family referenced blood samples sequenced in the course of forensic casework at the Armed Forces DNA Identification Laboratory (73 mtDNA lineages, 121 generational events)
• blood samples from the “Oxford” British families (five mtDNA lineages, 32 generational events)
• DNA from CEPH pedigree cell lines (16 mtDNA lienages, 94 generational events)
• DNA from Old Order Amish pedigree cell lines (40 mtDNA lineages, 80 generational events).

These sources allowed researchers to observe the mitochondrial DNA that was passed from mothers to their children, and to look for substitutions between the generations (Mitochondrial DNA is a more useful tool than looking at “regular” DNA because “regular” DNA has a high degree of crossover, whereas mtDNA does not).

Of the 327 generational events, 10 instances of substitution were observed. This suggests a rate of substituion of 2.5/site/Myr (95% confidence is 1.2-4.0/site/Myr). This rate is 10-100x faster than the rate usually assumed in phylogenic studies and is based on real data that you can go into the lab and repeatably analyze on modern humans.

There are a few explanations for the discrepancy

1. There is a flaw in the method used in this paper
2. Evolution is happening much faster than it usually does right now (the authors review a few possible nuances on this idea, e.g., mutation rates are high but natural selection weeds out most of these mutations and only a few mutations are “durable”)
3. The assumption in phylogenic studies (e.g., chimpanzees and humans have a common ancestor) is wrong

In any case, the authors say that based on their emprical measurement of mitochondrial mutation, the mtDNA molecular clock results “in an age of the mtDNA MRCA of only ~6,500 y.a., clearly incompatible with the known age of modern humans. Even acknowledging that the MCRA of mtDNA may be younger than the MRCA of modern humans, it remains implausible to explain the known geographic distributions of mtDNA sequence variation by human migration that occured only in the last ~6,500 years.” This is roughly consistent with a chronology that could be derived from the Bible (e.g., Ussher’s Chronology)

See a related article on mitochondrial bottlenecking