The latest issue of The Quarterly Review of Biology has a paper by intelligent-design advocate Michael Behe, “Experimental evolution, loss-of-function mutations, and “the first rule of adaptive evolution.” It’s a review of several decades’ worth of experimental evolution in microbes (viruses and bacteria), with an eye toward revealing exactly what kinds of mutations have occurred in these studies. He concludes that microbial evolution in the lab has been based largely on mutations that either 1) degrade or destroy functional elements like genes and promoter sequences, or 2) “modify” the function of pre-existing genetic elements so they do something slightly but not qualitatively different. What Behe does not observe is the evolution of “new functional elements” (see below): new genes, new coding sequences, new promoter regions, and the like.
When Behe produces a paper like this, it’s hard to resist imputing a motivation for the work. After all, the man has a long history of promoting ID, and has written two books (which I’ve reviewed—negatively—here and here [click “God in the details” at the bottom of the page]) purporting to show that a celestial hand was necessary in evolution. I’ve also caught Behe deliberately misquoting me in the service of his creationist views. I believe—and think that time will prove me right —that his intention is to show that evolution cannot provide new structures or new “information” (e.g., genes), but can only either tinker with ones already present or degrade them. Thus, to explain the evolution of truly new genetic information, one must invoke the intervention of an intelligent designer.
I think that while Behe’s summary of the results of these short-term lab experiments is generally accurate, one would be completely off the mark to extend his conclusions to evolution in general—that is, evolution as it has occurred in nature, be it in microbes or eukaryotes.
To make a long paper short, let me give the definitions Behe uses to reach his conclusion.
These are the things Behe doesn’t see arising in lab experiments:
Functional Coded elemenTs (FCTs): “An FCT is a discrete but not necessarily contiguous region of a gene that, by means of its nucleotide sequence, influences the production, processing, or biological activity of a particular nucleic acid or protein, or its specific binding to another molecule. Examples of FCTs are: promoters; enhancers; insulators; Shine-Dalgarno sequences; tRNA genes; miRNA genes; protein coding sequences; organellar targeting- or localization-signals; intron/extron splice sites; codons specifying the binding site of a protein for another molecule (such as its substrate, another protein, or a small allosteric regulator); codons specifying a processing site of a protein (such as a cleavage, myristoylation, or phosphorylation site); polyadenylation signals; and transcription and translation termination signals.”
In other other words, FCTs are new genes or new parts of genes, including those genetic changes that produce proteins with qualitatively new functions, not just a change in protein amount (e.g., changes in splicing or phosphorylation sites).
According to Behe, there are three types of adaptive genetic mutations that can be seen as differing in their effects on FCTs:
1. “Loss-of-FCT” mutations. Those are the changes that have adaptive effects by destroying or degrading an FCT. These include frame-shift mutations that render a protein inactive, or mutations that destroy a gene’s ability to bind to a transcription factor.
2. “Gain-of-FCT” mutations. These are the ones that Behe doesn’t see. He defines them as mutations “that produce a specific, new, functional coded element while adapting an organism to its environment. The construction by mutation of a new promoter, intron/exon splice site, or protein processing site are gain-of-FCT mutations. Also included in this category is the divergence by mutation of the activity of a previously duplicated coded element.” In other words, mutations in this category produce new genes, parts of genes, or confer drastic new capabilities on genes by adding new splicing sites. Also note that because almost no bacteria or viruses have introns in their cellular genes, it’s impossible to even see one class of this mutation in lab experiments on these groups.
3. “Modification-of-function” mutations. These include every adaptive mutation that doesn’t fall in the above two categories, including point mutations that affect protein structure or quantitatively affect protein quantity, gene duplications that occur without sequence divergence, rearrangements of gene order, etc. He calls these “modification of function” rather than “modification of FCT” because the functional change doesn’t have to occur by changing an FCT itself.
Now these categories are not cut and dried. For example, the “sickle-cell” mutation that, when present in one copy, protects carriers against malaria, is a point mutation in the beta hemoglobin molecule, changing a glutamic acid residue to a valine. You’d think that this would fall under class 3 (“point mutations”), but Behe considers it an adaptive gain of an FCT because the mutation causes the mutant hemoglobins to stick to each other in blood cells, somehow inhibiting the growth of the malaria parasite. And because the point mutation is thereby said to specify a “new protein binding site”, Behe puts it into class 2 (gain of FCT). Unfortunately, a lot of the single-gene mutations that Behe reviews from the experimental microbial-evolution literature work in unknown ways, so he could be missing similar cases that really fall into class 2.
Anyway, Behe reviews the last four decades of work on experimental evolution in bacteria and viruses (phage), and finds that nearly all the adaptive mutations in these studies fall into classes 1 and 3. We see very few “gain of FCT” mutations. Although this is not my field, the review seems pretty thorough to me, and the conclusions, as far as they apply to lab studies of adaptation in viruses and bacteria, seem sound. From this Behe formulates what he calls “The First Rule of Adaptive Evolution:
Break or blunt any functional coded element whose loss would yield a net fitness gain.
What this means is that if adaptation can be gained by losing gene or enzyme activity, it’s more likely to occur by a loss-of-FCT mutation than the appearance of a new FCT itself with altered and reduced function. That’s not really a “law” but a generalization from these lab experiments.
My overall conclusion: Behe has provided a useful survey of mutations that cause adaptation in short-term lab experiments on microbes (note that at least one of these—Rich Lenski’s study— extends over several decades). But his conclusions may be misleading when you extend them to bacterial or viral evolution in nature, and are certainly misleading if you extend them to eukaryotes (organisms with complex cells), for several reasons:
1. In virtually none of the experiments summarized by Behe was there the possibility of adapting the way that many bacteria and viruses actually adapt in nature: by the uptake of DNA from other microbes. Lenski’s studies of E. coli, for instance, and Bull’s work on phage evolution, deliberately preclude the presence of other species that could serve as vectors of DNA, and thus of new FCTs. This is not an idle objection, since we know that adaptation in natural populations of microbes often arises by incorporating new FCTs from other species. Pathogenicity and antibiotic resistance in bacteria, for example, arise in this way. Howard Ochman at Yale has done many studies on the acquisition of new bacterial functions by uptake of DNA from other species (and the source of the new DNA is often mysterious).
2. In relatively short-term lab experiments there has simply not been enough time to observe the accumulation of complex FCTs, which take time to build or acquire from a rare horizontal transmission event. Finding adaptation via point mutations or loss of function is much more likely. Behe admits this much, but downplays it by saying this:
After all, one certainly would not expect new genes with complex new properties to arise on such short time-scales. Although it is true that new complex gain-of-FCT mutations are not expected to occur on short time-scales, the importance of experimental studies to our understanding of adaptation lies elsewhere. Leaving aside gain-of-FCT for the moment, the work reviewed here shows that organisms do indeed adapt quickly in the laboratory—by loss-of-FCT and modification-of-function mutations. If such adaptive mutations also arrive first in the wild, as they of course would be expected to, then those will also be the kinds of mutations that are first available to selection in nature. This is a significant addition to our understanding of adaptation.
A third objection could be that the time and population scales of even the most ambitious laboratory evolution experiments are dwarfed when compared to those of nature. It is certainly true that, over the long course of history, many critical gain-of-FCT events occurred. However, that does not lessen our understanding, based upon work by many laboratories over the course of decades, of how evolution works in the short term, or of how the incessant background of loss-of-FCT mutations may influence adaptation.
What he’s saying is this: “Yes, gain of FCTs could, and likely is, more important in nature than seen in these short-term experiments. But my conclusions are limited to these types of short-term lab studies.” Well, good, but then let us not hear Behe’s ID colleagues tout these results as giving strong conclusions about microbial or eukyaryotic evolution in nature, particularly because the lab studies deliberately exclude sources of gain-of-FCT mutations that we know are important in nature.
3. Finally, Behe does not mention—and I think he should have—the extensive and very strong evidence for adaptation via gain-of-FCT mutations in eukaryotes. While that group may occasionally acquire genes or genetic elements by horizontal transfer, we know that they acquire new genes by the mechanism of gene duplication and divergence: new genes arise by duplication of old ones, and then the functions of these once-identical genes diverge as they acquire new mutations. Or, new genes can arise by unequal crossing-over between different genes, so that new genes arise by mixing bits of old ones. Behe would count both of these as type 2 mutations (“gain of FCT”). Think of all the genes that have arisen in eukaryotes in this way and gained novel function: classic examples include genes of the immune system, Hox gene families, olfactory genes, and the globin genes. And in many cases the origin of new genes via duplication or swapping of bits is untraceable because the genes originated so long ago and have diverged so greatly in sequence that their origin is obscure.
Vertebrates are thought to be the product of two whole-genome duplication events, giving rise to many genes with novel functions. This has probably happened in yeast at least once, and many plants are the results of ancient “polyploidy” events in which entire genomes were duplicated at least once. More than 40% of the genes in the human genome arose via gene duplications; this rises to more than 75% if we count those ancient rounds of whole-genome duplication. And over a third of the genes in the invertebrate Drosophila genome arose via duplication, with most of these having new functions. There are many, many papers describing and discussing the importance of duplicated genes (and regulatory elements) as a source of evolutionary novelty; see, for example, Long et al. (2003), Wray et al. (2003), and Kaessmann et al. (2009).
While Behe’s study is useful in summarizing how adaptive evolution has operated over the short term in bacteria and viruses in the lab, it’s far less useful in summarizing how evolution has happened over the longer term in bacteria or viruses in nature—or in eukaryotes in nature. In this sense it says nothing about whether new genes and gene functions have been important in the evolution of life. Granted, Behe doesn’t make such a sweeping statement—his paper wouldn’t have been published if he had—but there’s no doubt that his intelligent-design acolytes will use the paper in this way.
Finally, this paper gives ID advocates no reason to crow that a peer-reviewed paper supporting intelligent design has finally appeared in the scientific literature. The paper says absolutely nothing—zilch—that supports any contention of ID “theory.”
Behe, M. 2010. Experimental evolution, loss-of-function mutations, and “the first rule of adaptive evolution. Quart. Rev. Biol. 85:419-445.Kaessmann, H., N. Vinckenbosch, and M. Y. Long. 2009. RNA-based gene duplication: mechanistic and evolutionary insights. Nature Reviews Genetics 10:19-31.
Kaessmann, H., N. Vinckenbosch, and M. Y. Long. 2009. RNA-based gene duplication: mechanistic and evolutionary insights. Nature Reviews Genetics 10:19-31.
Long, M., E. Betran, K. Thornton, and W. Wang. 2003. The origin of new genes: Glimpses from the young and old. Nature Reviews Genetics 4:865-875.
Wray, G. A., M. W. Hahn, E. Abouheif, J. P. Balhoff, M. Pizer, M. V. Rockman, and L. A. Romano. 2003. The evolution of transcriptional regulation in eukaryotes. Molecular Biology and Evolution 20:1377-1419.