Sunday, November 22, 2009

From Best to Worst?: (Another) Reevaluation of mtDNA as a Molecular Marker

ResearchBlogging.orgOnce the golden child of molecular phylogenetic and phylogeographic analyses, mtDNA has taken a beating over the past five years. There is a bit of irony to this backlash: many of the features that were once thought to make mtDNA a particularly desirable marker (e.g., lack of recombination, maternal inheritance, low effective population size), are now being cited as contributors to its worst problems, introgression and discordance with species boundaries being two of the most serious. Although discussion of these problems isn't hard to come by (1, 2), Galtier et al.'s recent review in Molecular Ecology is a particularly insightful contribution.

Galtier et al. use a myth-busting review of the recent literature to investigate three widespread claims about mtDNA: strict clonal evolution (lack of recombination), selective neutrality, and constant mutation rate. Galtier et al.'s take on clonal evolution provides one of few encouraging findings: although numerous recent studies recover within-species homoplasy that may be interpreted as evidence for recombination, Galtier et al. suggest that this apparent homoplasy may also result from mutational hot-spots.

The suggestion that mtDNA is selectively neutral is an assumption that is most in need of a good thrashing, and Galtier et al. are happy to oblige. After a brief discussion of the powerful evidence for selection and selective sweeps, Galtier et al. provide a nice discussion of both the possible causes for these phenomena and their far-reaching implications. The last paragraph of this section sums things up rather nicely: "Whatever the underlying causes of the patterns [of selection] observed, these studies demonstrate that the withinspecies level of mtDNA diversity per se is not a good marker of population size and species health, as observed both at the metazoa and mammalian levels. Nonequilibrium processes apparently dominate. The classical interpretation of genetic diversity as the product of mutation rate by population size, as expected at mutation-drift equilibrium, is strongly questionable as far as mtDNA data are concerned."

Finally, Galtier et al. provide evidence - primarily from Nabholz et al.'s (2008) recent reviews (1, 2) - that rates of mtDNA evolution are widely variable, both within and among taxa. They conclude suggesting: "The molecular clock, therefore, is certainly not a tenable assumption as far as mtDNA is concerned. Nonclock- like evolution is common, and the departure from homogeneous rates can be very strong."

Conspicuously absent from Galtier et al.'s review is a discussion of the feature of mtDNA that has most challenged recent phylogenetic and phylogeographic studies: introgression. Perhaps Galtier et al. viewed this as a topic already addressed by other reviews, but the mechanisms underling mtDNA introgression remain poorly understood and this topic too would have benefitted from Galtier et al.'s insight.

At the end of the day, Galtier et al. take a rather dire view of mtDNA as a molecular marker, suggesting that its primary value is in its cheapness. Although I have a bit more charitable view, I certaintly hope that Galtier et al.'s review will succeed in opening more eyes to the diversity of problems confronting interpretation of mtDNA.

GALTIER, N., NABHOLZ, B., GLÉMIN, S., & HURST, G. (2009). Mitochondrial DNA as a marker of molecular diversity: a reappraisal Molecular Ecology, 18 (22), 4541-4550 DOI: 10.1111/j.1365-294X.2009.04380.x


Kevin Zelnio said...

I apologize in advance that is not a comment on the content, which I thoroughly enjoyed since I get into pissing matches with my boss over his blinding use of COI for everything. I've been a long time reader and enjoy posts such as these, discussing peer reviewed literature.

Have you heard about ResearchBlogging? We aggregate blog posts on peer-reviewed by using the DOI of a journal article. This aggregation is read by many people subscribing to various channels on RSS feed and we now have customizable widgets that posts appear on.

I am an admin for the site and am happy to answer any questions, just email me. It would be fantastic to have more high quality blogs like Dechronization on there. We have nearly 1000 excellent science blogs already! The goal is to encourage discussion of peer-reviewed literature in the public realm where everyone can participate and learn.

Liam Revell said...

What are the varied possible "mechanisms underling mtDNA introgression?" Obviously, incongruence between the estimated gene genealogy and the phylogeny can have multiple causes. However, it seems to me that mtDNA introgression should only come from one source - hybridization. Maybe there are many interesting phenomena associated with mtDNA introgression (such as selective sweeps of introgressed haplotypes, and what not), or perhaps I'm missing the point entirely. Please elaborate.

Glor said...

The mechanisms I was speaking of are those that might explain why mtDNA appears to introgress more readily than other molecular markers. Although this marker's small effective population size and lack of recombination seem to play an important role, the potential importance of phenomena like selective sweeps and asymmetric hybridization remain poorly understood (IMO).

Thanks for the suggestion. I actually signed up for researchblogging over a year ago, but never got in the habit of registering posts. I'll kick things off with this post!

Liam Revell said...

Rich. Interesting . . . .

Glor said...

More on mtDNA, and how it violated simple null assumptions in population genetics in Wares's paper just published in Evolution. The final word from Wares "many researchers in the fields of molecular ecology and phylogeography routinely apply tests such as DT while assuming neutrality so that demographic inferences about their populations can be made. It is clear that without full consideration of the evolutionary history of a population, such demographic inference can be inaccurate or misleading. In the case of the results shown here, the generality of negative DT values suggests that inference of population history from such tests will require more sophisticated evaluation, and additional genomic data."

Glor said...

...and another example of the potential powerful influence of natural selection on mtDNA haplotypes: mothers' curse.

sergios-orestis kolokotronis said...

Now that you mention cytonuclear incompatibility, I recall Engelstädter & Charlat's 2006 paper, where they model the spread and impact of spiteful cytotypes on population dynamics. Very interesting how they advance on Hamilton's spite concept.

Engelstädter J, Charlat S. (2006) Outbreeding selects for spiteful cytoplasmic elements. Proc Biol Sci 273(1589):923-929.

Hamilton WD. (1970) Selfish and spiteful behaviour in an evolutionary model. Nature 228:1218-1220.

These are all aspects we're very interested in at Mitochondrial DNA, so if anybody has a paper they'd like to send our way, do let me or Rob DeSalle know.