The latest round of vigorous debate in evolutionary biology has been featured in Science by reporter Elizabeth Pennisi, and it deals with the role of cis-regulatory sequences in evolution. cis what?, you might say. A cis regulatory sequence is a piece of DNA that is located outside of a gene proper (typically upstream of it), but located next to it on a chromosome. The cis element does not code for a protein or enzyme, unlike the gene itself, but rather alters the timing (during development) and place (which tissue) the gene itself gets expressed. cis is in opposition to another type of regulation of gene activity, known as trans, where a molecule produced in one part of the nucleus (by a particular sequence of DNA) affects the regulation of a gene far away, on a different part of the genome.
cis-regulatory sequences have received much attention lately, for instance by evolutionary biologist Sean Carroll of the University of Wisconsin-Madison, who is one of the leading researchers on so called “evo-devo” (evolutionary developmental biology). In 2005, Carroll wrote an influential paper in PLoS Biology, in which he argued that the action of cis-regulatory elements is crucial to morphological evolution in animals (though why only morphological? What about physiology, biochemistry, or other aspects of the phenotype?). The implication is that cis-regulatory evolution may be directly involved with the origin of several major “phenotypic novelties,” the sort of structures whose detailed explanation is one of the holy grails of evolutionary biology.
Just like in any good controversy, though, there is a group of people pushing for new ideas and another one playing the part of the intellectual conservative, resisting the change and declaring that what is being trumpeted as new is either already known or not much of a big deal. Sure enough, in 2007 the journal Evolution published a response to Carroll’s paper, co-authored by Jerry Coyne (University of Chicago) and Hopi Hoekstra (Harvard). Coyne, incidentally, has appeared in the role of the skeptic several times lately, most recently in another piece by Pennisi in Science, the one commenting on the so-called “Altenberg 16” meeting which I organized in Austria this summer (more on that meeting will soon appear in Nature magazine, again featuring Jerry as the counterpoint, in that case to my own positions).
Coyne and Hoekstra’s paper, according to Pennisi and some comentators, was sharply worded (indeed, Hoekstra herself regretted the strong language in the Science interview), and the Scientific American’s web site recently hosted an article by Carroll and colleagues that led to an interesting exchange (in the comments section) between Carroll and some readers (Coyne did not participate). However much the verbiage may have bruised egos or raised hairs, of course, the real controversy is about the empirical evidence and its interpretation: are cis-regulatory sequences that important in morphological evolution or not?
In part the answer depends on what one means by “important.” We do not have reliable data about the frequency of evolutionary changes triggered by mutations in cis-regulators vs. standard protein-coding genes, and it is unlikely that a large unbiased sample of enough genomes will be available any time soon to settle the matter in that sense. Then again, “importance” in biology is hardly a matter of sheer numbers: some evolutionarily relevant phenomena happen very rarely, and yet they are arguably very important in the sense that they affect the subsequent course of life’s history on the planet in remarkable ways. Think of impacts of extraterrestrial bodies and their link to mass extinction: sure, they happen once every several tens or even hundreds of millions of years, but the one at the end of the Cretaceous helped wipe out the dinosaurs and arguably led to the rapid ecological takeover of mammals.
In the cis dispute, Carroll brings up what I think is in fact compelling evidence that cis-regulation does play a crucial role in morphological evolution, at least some of the time. Coyne’s response is to demand more direct (less correlational) evidence before jumping to conclusions, and he has a point too. The reality is probably somewhere in the middle, as my colleague Gunter Wagner (one of the Altenberg 16) told Science: “There are clearly well-worked-out examples where microevolutionary changes can be traced back to cis-regulatory changes.” Greg Wray (another middle ground voice of reason, and yet another Altenberg 16 co-conspirator) said “I think we are on the threshold of a very exciting time.”
There are two points to be taken from this story, I think. First, social scientists ought to do serious studies of the role of personality in scientific disputes (it has probably been done already). Why is it, for instance, that people like Jerry Coyne tend to find themselves very often defending the conservative position, while people like, hum, me, find themselves on the other side of the barricade? Obviously, some of the times the conservatives will be right, at other times the progressives will be, so finding yourself more frequently than not in one category must have to do more with your psychology than with whether you tend to be right or not.
The second point, however, is about how science makes progress: we need both the Sean Carrolls and the Jerry Coynes of the world, not just because they make science more personal and, frankly, exciting, but because it is the tension between ideas that drives the whole enterprise. Some scientific controversies get settled by the data, others remain in permanent suspension because pertinent data isn’t forthcoming, and yet others change in nature over time because people shift conceptual framework and therefore come to think about old issues in new ways. This is entirely different from pseudosciences like intelligent design, where controversy undermines the ideological message, and where empirical facts have nothing to do with it. Of course, a psychological study of the creationist mind would also be fascinating, I can see the title of an fMRI paper already: “This is your brain on creationism”...