Below are quoted from the article Calibrating the Mitochondrial Clock by Ann Gibbons in News this Week, Science 02 Jan 1998, Vol. 279, Issue 5347, pp. 28:
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The most widely used mutation rate for noncoding human mtDNA relies on estimates of the date when humans and chimpanzees shared a common ancestor, taken to be 5 million years ago. That date is based on counting the mtDNA and protein differences between all the great apes and timing their divergence using dates from fossils of one great ape's ancestor. In humans, this yields a rate of about one mutation every 300 to 600 generations, or one every 6000 to 12,000 years (assuming a generation is 20 years), says molecular anthropologist Mark Stoneking of Pennsylvania State University in University Park. Those estimates are also calibrated with other archaeological dates, but nonetheless yield wide margins of error in published dates. But a few studies have begun to suggest that the actual rates are much faster, prompting researchers to think twice about the mtDNA clock they depend upon.
For example, after working on the tsar's DNA, Parsons was surprised to find heteroplasmy popping up more frequently than expected in the families of missing soldiers. He and his colleagues in the United States and England began a systematic study of mtDNA from soldiers' families and Amish and British families. Like most such studies, this one compares so-called “noncoding” sequences of the control region of mtDNA, which do not code for gene products and therefore are thought to be free from natural selection.
The researchers sequenced 610 base pairs of the mtDNA control region in 357 individuals from 134 different families, representing 327 generational events, or times that mothers passed on mtDNA to their offspring. Evolutionary studies led them to expect about one mutation in 600 generations (one every 12,000 years). So they were “stunned” to find 10 base-pair changes, which gave them a rate of one mutation every 40 generations, or one every 800 years. The data were published last year in Nature Genetics, and the rate has held up as the number of families has doubled, Parsons told scientists who gathered at a recent international workshop* on the problem of mtDNA mutation rates.
Howell's team independently arrived at a similar conclusion after looking deep within the pedigree of one Australian family affected with Leber hereditary optic neuropathy, a disease caused by an mtDNA gene mutation. When the researchers analyzed mtDNA from 40 members of this family, they found that one individual carried two mutations in the control region (presumably unrelated to the disease, because it is noncoding mtDNA). That condition is known as triplasmy, because including the nonmutated sequence, he had three different mtDNA sequences in his cells.
By tracing the mutations back through the family pedigree, Howell was able to estimate that both mutations probably arose in the same woman who was born in 1861, yielding an overall divergence rate of one mutation every 25 to 40 generations. “Both of our studies came to a remarkably similar conclusion,” says Howell, whose study was published in late 1996 in the American Journal of Human Genetics. Both also warned that phylogenetic studies have “substantially underestimated the rate of mtDNA divergence.”
Several teams of evolutionists promptly went back to their labs to count mtDNA mutations in families of known pedigree. So far, Stoneking's team has sequenced segments of the control region in closely related families on the Atlantic island of Tristan da Cunha, where pedigrees trace back to five female founders in the early 19th century. But neither that study nor one of 33 Swedish families has found a higher mutation rate. “After we read Howell's study, we looked in vain for mutations in our families,” says geneticist Ulf Gyllensten of Uppsala University in Sweden, whose results are in press in Nature Genetics. More work is under way in Polynesia, Israel, and Europe.
Troubled by the discrepancy in their results, the scientists have pooled their data with a few other studies showing heteroplasmy, hoping to glean a more accurate estimate of the overall mutation rate. According to papers in press by Parsons, and Stoneking and Gyllensten, the combined mutation rate—one mutation per 1200 years—is still higher than the one mutation per 6000 to 12,000 years estimated by evolutionists, although not as fast as the rate observed by Parsons and Howell. “The fact that we see such relatively large differences among studies indicates that we have some unknown variable which is causing this,” says Gyllensten.
Because few studies have been done, the discrepancy in rates could simply be a statistical artifact, in which case it should vanish as sample sizes grow larger, notes Eric Shoubridge, a molecular geneticist at the Montreal Neurological Institute. Another possibility is that the rate is higher in some sites of the DNA than others—so-called “hot spots.” Indeed, almost all the mutations detected in Parsons and Howell's studies occur at known hot spots, says University of Munich molecular geneticist Svante Pääbo.
Also, the time span of observation plays a role. For example, because hot spots mutate so frequently, over tens of thousands of years they can revert back to their original sequences, overwriting previous mutations at that site. As a result, the long-term mutation rate would underestimate how often hot spots mutate—and the average long-term mutation rate for the entire control region would be slower than that from near-term studies of families. “The easiest explanation is that these two rates are caused by hot spots,” says Pääbo.
If so, these short-term rates need not perturb long-term studies. “It may be that the faster rate works on the short time scale and that you use the phylogenetic rate for long-term events,” says Shoubridge.
But Parsons doubts that hot spots account for all the mutations he has observed. He says that some of the difference between the long-term and short-term rates could be explained if the noncoding DNA in the control region is not entirely immune to selection pressure. The control region, for example, promotes replication and transcription of mtDNA, so any mutation that interferes with the efficiency of these processes might be deleterious and therefore selected against, reducing the apparent mutation rate.
Regardless of the cause, evolutionists are most concerned about the effect of a faster mutation rate. For example, researchers have calculated that “mitochondrial Eve”—the woman whose mtDNA was ancestral to that in all living people—lived 100,000 to 200,000 years ago in Africa. Using the new clock, she would be a mere 6000 years old.
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