Mitochondrial genetic diversity may be influenced by natural selection, undermining its utility for population genetics research
By Charles Choi | April 28, 2006
One of the most widely used markers in population genetics, mitochondrial genetic diversity, does not accurately reflect the size and history of a population, according to a report in this week'sScience. This suggests natural selection may be acting on mitochondrial DNA (mtDNA), the authors note.
"This result opens questions -- what is mtDNA adapting to?" co-author Nicolas Galtier at the University of Montpellier in France told The Scientist.
MtDNA is widely believed to be nearly evolutionary neutral. Therefore, mitochondrial genetic diversity should increase as a species' population size increases, and looking at mtDNA diversity should enable researchers to infer whether a species is advancing or declining.
In the present study, the researchers assembled a database dedicated to sequence polymorphism by scanning GenBank and EMBL-Bank. To check its reliability, they compared the resulting information on the nuclear DNA of 417 species and the mtDNA of 1,683 species with allozyme data for 912 species, focusing on whether taxa with larger populations demonstrated higher diversity.
The authors intuited that average diversity should be higher in invertebrates than vertebrates, as well as higher in marine and small organisms, relative to terrestrial and larger organisms, respectively. Using nuclear DNA and allozyme data, the researchers saw that the average diversity of invertebrate taxa was four times higher than that of vertebrates -- the expected pattern. However, mitochondrial genetic diversity failed to reflect differences in expected average population size, instead staying remarkably similar across taxa.
Galtier and his colleagues suggest the pattern of diversity in mitochondria could be explained by natural selection. Some beneficial mutations can mute variation in linked loci, a process called "hitchhiking" that mtDNA is especially prone to because of its relative lack of recombination. The larger a population gets, the more opportunities there are to accumulate adaptive mtDNA mutations. More adaptive mutations could freeze more hitched loci, the authors reasoned, perhaps explaining why mtDNA diversity remained similar across taxa, regardless of population size.
Indeed, the authors found that 58% of amino acid substitutions appear adaptive in invertebrate mtDNA, compared to 12% in vertebrates, supporting their notion that the rate of adaptive evolution is proportional to population size. Natural selection pressures mitochondria could experience might include "the genomic conflict between mitochondrial and nuclear DNA," Galtier noted.
"It's really surprising to see so much adaptive evolution going on. You wouldn't expect it of mitochondria, which are so involved in central metabolism," Adam Eyre-Walker at the University of Sussex in England, who did not participate in this study, told The Scientist.
These findings "raise some very interesting questions," David Foltz at Louisiana State University in Baton Rouge, who did not participate in this study, told The Scientist. Follow-up should involve examining mtDNA diversity at lower taxonomic levels, to determine if population size has any effect, and investigating the role of life history factors such as mode of reproduction or generation time, he added.
David Rand of Brown University in Rhode Island, also not a co-author, described the paper as "a strong indictment of the use of mtDNA as a neutral marker." Still, he said he was concerned that the new study ignored rare polymorphisms, which would bias results toward positive selection. "It would be useful to repeat the analyses with all polymorphisms included to see if the difference between invertebrates and vertebrates is upheld."
Interestingly, humans do not display the same pattern Galtier and his colleagues found, Eyre-Walker noted -- suggesting humans may have such a small population that adaptive evolution in the mitochondrial genome is very rare. "If you can find species like ours that likely have not undergone much adaptive evolution in their mitochondria, such as (the) other great apes, then it'd be interesting to look for a correlation between diversity and population size," Eyre-Walker said.
Charles Q. Choi
Links within this article
E. Bazin et al. "Population size does not influence mitochondrial genetic diversity in animals." Science, April 28, 2006.
D. Steinberg, "Genetic variation illuminates murky human history," The Scientist, July 24, 2000.
D. Steinberg, "How did natural selection shape human genes?" The Scientist, May 10, 2004.