Two patients who died from avian influenza in Vietnam had developed resistance to the antiviral drug Tamiflu, scientists are reporting today.
The cases bring to three the number of Tamiflu-resistant cases among 138 people known to have been infected with the A (H5N1) avian influenza virus, according to the World Health Organization. Of these, 71 have died.
All cases of human infection have been reported from Southeast Asia and with rare exception are believed to have resulted from contact with infected birds. All three Tamiflu-resistant cases occurred in Vietnam.
The findings, which are being reported in The New England Journal of Medicine, show that the virus can rapidly mutate in certain patients to become Tamiflu resistant. Tamiflu might need to be given in larger amounts and for longer than currently recommended for human influenza viruses, the report said. It also said Tamiflu might need to be used in combination with other drugs in some cases.
How did this happen?
Why, through evolution, the scientific breakthrough of 2005. Of course, Science focusses on big, happy stories like the comparison of the human and chimpanzee chromosomes, but avian flu sneaks in.
Also highlighted: several new instances of speciation at work, and evolution of other diseases.
I want to talk about one study that isn’t getting all the press from the big guys: sticklebacks.
In Canada, Scotland, and other northern areas, oceanic sticklebacks have moved into glacial lakes.
In some lakes, you find one species, in other lakes, you find two species. We can show that in each lake, the two species that coexist share a more recent common ancestor with each other than with any fish in other lakes. This is a massive series of parallel speciation events.
Even more remarkably, when there are two species in a lake, the two are always from two distinct types (ecomorphs), and the same distinct types occur across all the lakes. There are larger, spinier fish that use the open middle of the lake, and smaller, lither fish that hang around in the plants at the edge.
A few years back, Dolph Schluter (familiar to readers of The Beak of the Finch by Jonathan Weiner) hybridized individuals from the two strains to get something like the ancestral species, then turned them loose in artificial ponds. Half of each pond had the smaller, edge-dwelling species in it, half had only the hybrids. In the control half, the hybrids stayed the same size, while in the treatment halves, the smaller hybrids grow more slowly, while larger ones grew normally. This indicates that competition drives the two ecomorphs apart. The fact that the pattern repeats indicates that the same event happened dozens of times, in Canada, Japan, Ireland and Scotland.
Because it’s such a striking example of speciation at work, there’s a lot of research that’s been done on the mechanism at work in this change.
In a paper published this year in Science, researchers including Schluter show that the same gene has been under intense selection in sticklebacks in Canada, Europe and Japan.
Gene predictions show that the marker at the peak of linkage disequilibrium is located within intron 2 of the stickleback Ectodysplasin (Eda) gene. EDA is a member of the tumor necrosis family of secreted signaling molecules and, in mammals, is required for proper development of a number of ectodermal derivatives (e.g., teeth, hair, and sweat glands) and dermal bones (21, 22). Previous studies have shown that a mutation in the Ectodysplasin receptor (Edar) gene in medaka (Oryzias latipes) causes loss of most scales (23), which are elements of the dermal skeleton (24). Many elements of the dermal skeleton in fishes, including scales and the dermal lateral plates of sticklebacks, have likely evolved from a common ancestral element (24). The position of Eda at the peak of linkage disequilibrium in the stickleback candidate interval and the known role of EDA signaling in scale formation suggested that changes in the Eda locus may underlie the molecular basis of plate morph evolution in sticklebacks.
To translate, they figured out exactly where on the chromosome the changes were happening. The gene involved is conserved across vertebrates, influencing not only scale growth, but hair, teeth, and sweat glands in mammals.
The researchers then looked at sequence differences for that gene and for other genes. Figure A shows the locations sampled. Red labels indicate the normal fish, blue are the specialized fish.
Figure B shows a phylogeny for only the gene suspected of controlling the lower scale count. You can see that fish of similar phenotype are more similar for that gene, with the exception of one population from Japan.
However, when you look at 25 randomly chosen nuclear genes. You get a clear geographic split, with spatially closer species closer on the phylogeny and no clear pattern to the distribution of the morphs.
This, of course, is exactly what you expect. Looking at random genes means that any selection ought to be random in the cumulative effect, while looking at the gene which controls the phenotype should reveal exactly this pattern if parallel evolution is happening.
It’s fascinating biology. The sort of speciation (or incipient speciation, depending how you define things) we see here is somewhat unexpected, because it happens while both species are in contact with each other. If this sort of thing is common, it opens up interesting intersections of evolution and ecological theory.
Either way, it reveals one way that evolution is predictable and has repeated itself many times in different places.