Not So Many Pathways: Response to Carl Zimmer and Joseph Thornton

Michael Behe

The science writer Carl Zimmer posted an invited reply on his blog from Joseph Thornton of the University of Oregon to my recent comments about Thornton’s work. This is the second of several posts addressing it. References will appear in the last post.
Now to Professor Thornton’s reply. He writes at length but makes just two substantive points: 1) that neutral mutations occur and can serendipitously help a protein evolve some function (“[Behe] ignores the key role of genetic drift in evolution”); and 2) that just because a protein may not be able to evolve a particular function one way does not mean that it, or some other kind of protein, can’t evolve the function another way (“nothing in our results implies that, if selection were to favor the ancestral function again, the protein could not adapt by evolving a different, convergent, underlying basis for the function”).
I’ll start with the second point since I can just quote myself to answer it. I wrote in one of my previous posts on Thornton’s work:

Another point worth driving home in this post concerns the frequently encountered argument that, well, just because one kind of protein can’t develop a useful binding site or selectable property easily doesn’t mean that some other kind of cellular protein can’t. (In keeping with their Darwinian framework, Bridgham et al (2009) seem to allude to this.) After all, there are thousands to tens of thousands of kinds of proteins in a typical cell. If one of them is ruled out, the reasoning goes, many more possibilities remain.
This argument, however, is specious. For any given evolutionary task, the number of proteins in the cell which are candidates for helpful mutations is almost always very limited. For example, as I discussed in EOE, out of thousands of malaria proteins, mutations in only a handful are helpful to the parasite in its fight against chloroquine, and only one is really effective — the mutations in the PfCRT protein. Ditto for the human proteins that can mutate to help resist malaria — there’s just a handful. In the case of the hormone receptors discussed by Bridgham et al (2006), one can note that, out of ten thousand vertebrate proteins, the one that gave rise to a new steroid hormone receptor was an already-existing steroid hormone receptor. This should be quite surprising to folks who believe the many-proteins argument, because the steroid receptor was outnumbered 10,000 to 1 by other protein genes, yet it won the race to duplicate and form a new functional receptor. If all things were equal, we should be very surprised by that. But of course not all things are equal. The reason the receptor duplicated to give rise to a closely-related receptor is because no other protein in the cell is likely to be able to do so in a reasonable amount of evolutionary time.

(Professor Thornton’s post gives no indication that he read this; he certainly gave no response to it.) If the most likely candidate protein has difficulty evolving to yield a given function by the most likely candidate route, there may (or may not) be another, less likely route, or a handful of other less likely candidate proteins that could do so, but there is certainly not a huge reservoir of possibilities, as Thornton seems to think. And, for those who believe this all depends on blind luck, most of the time things should not turn out well at all.
Now let’s contrast Thornton’s blog reply to me with what he wrote in his paper. In the blog he writes: “nothing in our results implies that, if selection were to favor the ancestral function again, the protein could not adapt by evolving a different, convergent, underlying basis for the function.” Yet in his paper he wrote:

There may be other potentially permissive mutations, of unknown number, that could compensate for the restrictive effect of group W and allow the ancestral conformation to be restored. Reversal by such indirect pathways could be driven by selection, however, only if these other mutations, unlike those we studied, could somehow relieve the steric clashes and restore the lost stabilizing interactions … and also independently restore the ancestral function when helix 7 is in its radically different derived conformation. Whether or not mutations that could achieve these dual ends exist, reversal to the ancestral conformation would require a considerably more complex pathway than was necessary before the ratchet effect of W evolved.

Professor Thornton is playing games. The strongly-emphasized point of his paper was to show exactly what I discussed in my posts: the extreme improbability (not “impossibility,” which is for suckers — one can’t prove a negative in science) of re-acquiring the ancestral structure/ function, either by direct or indirect reversal.

Michael J. Behe

Senior Fellow, Center for Science and Culture
Michael J. Behe is Professor of Biological Sciences at Lehigh University in Pennsylvania and a Senior Fellow at Discovery Institute’s Center for Science and Culture. He received his Ph.D. in Biochemistry from the University of Pennsylvania in 1978. Behe's current research involves delineation of design and natural selection in protein structures. In his career he has authored over 40 technical papers and three books, Darwin Devolves: The New Science About DNA that Challenges Evolution, Darwin’s Black Box: The Biochemical Challenge to Evolution, and The Edge of Evolution: The Search for the Limits of Darwinism, which argue that living system at the molecular level are best explained as being the result of deliberate intelligent design.