Showing posts with label natural selection. Show all posts
Showing posts with label natural selection. Show all posts

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

Wednesday, April 29, 2009

The Importance of Understanding Evolution for Public Health

While lots of people are scrambling to make [good] phylogenetic trees of the new swine flu sequences in the context of other flu viruses, another paper came out in this week's PLoS Biology that presents a really powerful argument for incorporating evolution into public health. Andrew Read, of Penn State University, and others both at Penn State and at the Open University in the U.K. just published the results of their work on late-life acting (LLA) insecticides, arguing that if you understand a little bit about natural selection, you just might be able to profoundly stack the deck in the global battle against malaria. Mosquitoes as a whole, suffer a high mortality rate - according to Read et al., the figure is around 10% per day or 20-40% per gonotrophic, or egg-laying, cycle. In order to transmit malaria, a mosquito must take one blood meal from an infected person and then survive long enough to need a second one, with the interval between these events being long enough for the parasite to develop to an infective stage. Because development to the infective stage typically takes 10-14 days in malaria-endemic regions, very few infected mosquitoes live long enough to actually vector the disease. The paper argues that conventional insecticides such as DDT and pyrethroids, classes of which are "early-acting" insecticides that kill 80% of mosquitoes they come into contact with, exert tremendous selection pressure on mosquitoes to evolve resistance, because they are robbing a large proportion of the whole population of all of their fitness. Conversely, LLA insecticides, which kill mosquitoes after their first gonotrophic cycle, impose far less natural selection and thus the corresponding selection for resistance is slower to evolve. Crunching some numbers allowed Read et al. to show that an insecticide that killed mosquitoes after 2 or more gonotrophic cycles could reduce the number of malaria-infectious bites by 99.2%. Even the insecticides that took longer to kill mosquitoes still showed drastic reductions: the 4-cycle killers showed a 94.2% drop in deadly bloodmeals. Because evolution of resistance itself bears fitness costs to mosquitoes, LLA could allow for some insecticides to be "evolution proof" - i.e. the time it would take for mosquitoes to evolve resistance to these sprays would be so long as to essentially be immortal.

Hopefully this study and others like it (e.g. Wargo et al., 2007) will be carefully read by those making public health decisions - because thinking long-term - in an evolutionary sense, not just a medical sense - is absolutely critical. And if you're not a public health official, read these studies anyway - they make great examples for teaching the importance of evolution to everyday life.