This is the third in a series of posts responding to the extended critique of Darwin Devolves by Richard Lenski at his blog, Telliamed Revisited. Professor Lenski is perhaps the most qualified scientist in the world to analyze the arguments of my book. He is the Hannah Distinguished Professor of Microbial Ecology at Michigan State University, a MacArthur (“Genius Award”) Fellow, and a member of the National Academy of Sciences with hundreds of publications. He also has a strong interest in the history and philosophy of science. His own laboratory evolution work is a central focus of the book. I am very grateful to Professor Lenski for taking time to assess Darwin Devolves. His comments will allow interested readers to quickly gauge the relative strength of arguments against the book’s thesis.
I have already addressed several of the issues that Lenski has raised at his blog in his third post on Darwin Devolves, “Is the LTEE Breaking Bad?,” in my responses (here, here, and here) to the review by my Lehigh colleagues, because they cited his work frequently. Nonetheless, repetition is a fine teaching tool. So here I will again speak to those issues and also address a few others.
In “Is the LTEE Breaking Bad?” Lenski agrees that the beneficial mutations seen in his Long Term Evolution Experiment are overwhelmingly degradative or loss-of-function ones. Even so, that does not concern him because “the LTEE represents an ideal system in which to observe degradative evolution.” Beneficial degradative changes are only to be expected there, it seems.
The LTEE was designed (intelligently, in my opinion!) to be extremely simple in order to address some basic questions about the dynamics and repeatability of evolution, while minimizing complications. It was not intended to mimic the complexities of nature, nor was it meant to be a test-bed for the evolution of new functions. The environment in which the bacteria grow is extremely simple. …
Indeed, the LTEE environment is so extremely simple that one might reasonably expect the bacteria would evolve by breaking many existing functions. That is because the cells could, without consequence, lose their abilities to exploit resources not present in the flasks, lose their defenses against absent predators and competitors, and lose their capacities to withstand no-longer-relevant extreme temperatures, bile salts, antibiotics, and more. [Emphasis in the original.]
In other words, there are many tools in the robust E. coli genomic toolbox that wouldn’t be needed in the Michigan State lab. It could lose them without immediate consequence. In fact, there may even be some benefit to losing them, either by simply saving the energy of making them, or by diverting resources to other pathways that are more heavily used in the lab environment.
Yet one inevitable consequence of losing genes is losing flexibility — while the parent bacterial strain could evolve to live in the lab environment, the mutant bacteria can’t go home again. If their environment shifted back to the more complex, more hostile one from which they had been taken, they would no longer be competitive. Thus as a strong rule we would expect situations in which any species — not just E. coli — either in the lab or in the wild, adapt by losing genes to simultaneously be limiting their ability to adapt to future environmental changes. Just as the lab E. coli is becoming more environmentally restricted as it loses more genes, the examples from the wild of the polar bear and Yersinia pestis that I cited in Darwin Devolves are, too.
As quoted above, Professor Lenski set up the LTEE to probe “basic questions about the dynamics … of evolution.” One basic dynamic that the results show with great clarity is that beneficial degradative mutations occur orders of magnitude faster than beneficial non-degradative ones. Beneficial degradative mutations such as destruction of the ribose operon occurred in about a hundred generations. On the other hand, the pokey non-degradative citrate mutation appeared only after 30,000 generations. In terms of sheer growth in the lab environment, it helped the bacteria very much more than any of the degradative ones — the citrate mutants completely took over the colony overnight. Nonetheless, the citrate mutation appeared only well after maybe a dozen mutations that degraded genes had already swept to fixation, permanently restricting the bacterial strain.
Why is that? The citrate mutation was much slower to appear, of course, because it required more exacting, less probable conditions that necessarily occur much less frequently. As a rule, all non-degradative mutations will be less frequent than degradative ones. So one very important dynamic result that the LTEE makes crystal clear is that degradative mutations arrive very rapidly, constructive ones much more slowly. In other words, any and all helpful degradative changes will have the time they need to take over a population well before the arrival of particular non-degradative changes, such as the citrate mutation.
The Significance of Citrate
Professor Lenski thinks the citrate mutation is a good example of the constructive power of evolution. Yet he considers it in isolation and overlooks the overwhelmingly degradative context surrounding that event.
To his credit, Behe does write about the lineage that evolved the ability to consume the citrate. However, he dismisses it as a “sideshow” (p. 365 [sic, actually p. 190]), because he refuses to call this new capability a gain of function. Instead, Behe writes (p. 362 [sic, actually p. 189]) that under his self-fulfilling scheme “the mutation would be counted as modification-of-function — because no new functional coded element was gained or lost, just copied.” In other words, Behe won’t count any newly evolved function as a gain of function unless some entirely new gene or control region “poofs” into existence. [Emphasis in the original.]
I didn’t mean to hurt Professor Lenski’s feelings with that “sideshow” remark about the citrate mutation. I’m more than happy to agree that it was a very interesting development in the lab evolution project. However, as I’ve written before, I called it a “sideshow” because it was preceded by many degradative mutations and succeeded by several more that enhanced its efficacy. Compared to degradative mutations, it was numerically swamped. In my view, by far the most important point is that helpful degradative mutations appear so fast compared to constructive ones that they will swarm after any change in the environment, quickly adapting an organism. That’s exactly what we should expect from the First Rule of Adaptive Evolution. If a lucky constructive mutation — occasionally, eventually — comes along, too, well, that’s nice, but it doesn’t undo the damage done by poison-pill mutations.
The LTEE is Poof-less
As for Professor Lenski’s complaint that “Behe won’t count any newly evolved function as a gain of function unless some entirely new gene or control region ‘poofs’ into existence” (boldface removed), he is incorrect. In both my Quarterly Review of Biology paper and Darwin Devolves I counted the sickle cell mutation (a single amino-acid change) of hemoglobin as gain-of-FCT (FCT stands for “Functional-Coded-elemenT), because it resulted in a new protein-protein binding site. As I explained at length in both places, I classified mutations according to their molecular effects — not their phenotypic effects — according to whether they resulted in the gain or loss of such functional coded elements as:
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 order to properly evaluate Darwin’s mechanism, one has to observe what it does at the molecular level in terms of coded genetic elements. Many careful studies document that it overwhelmingly degrades them. No new such elements were seen in the LTEE.
Over 90 Percent Degradative Qualifies as “Chiefly”
Professor Lenski tries to shield at least some of the beneficial mutations of the LTEE from being labeled as degradative.
In Darwin Devolves, Behe asserts (p. 344 [sic, actually p. 179]) that “it’s very likely that all of the identified beneficial mutations worked by degrading or outright breaking the respective ancestor genes.” He includes a footnote that acknowledges our work that suggests the fine-tuning of some protein functions, but there he writes (p. 609): “More recent investigation by Lenski’s lab suggests that mutations in a small minority (10 of 57) of selected E. coli genes may not completely break them but rather, as they put it, ‘fine-tune’ them (probably by degrading their functions).” Why does Behe assert that fine-tuning of genes occurred “probably by degrading their functions”?
Perhaps it’s because this assertion supports his claim, but more charitably I suspect the underlying reason is similar to the problematic inferences that got Behe into trouble in the case of the polar bear’s genes. That is, if one assumes the ancestral state of a gene is perfect, then there’s no room for improvement in its function, and the only possible functional changes are degradative. … It would be surprising if some proteins couldn’t be fine-tuned such that their activities were improved under the particular pH, temperature, osmolarity, and other conditions of the LTEE.
Several comments. First, the polar bear. It turns out that Lenski and his unreliable sources were grasping at straws in trying to avoid the straightforward conclusion that the degradation of the polar bear APOB protein actually helped it to tolerate a high fat diet. The same effect is seen in mice when one copy of the gene is knocked out.
Second, I agree that one should expect some fine-tuning in the LTEE. Yet, if “only” 47 of 57 beneficial mutations worked by degrading or destroying genes in the LTEE project, I would consider my argument to be quite fully vindicated. After all, I never claimed that all beneficial mutations must be degradative. The First Rule of Adaptive Evolution is probabilistic, not prescriptive.
Third, as for why I considered the remaining selected proteins to probably be degrading, the reasons can be found in Lenski’s paper itself. Three of the ten (nadR, pykF, and yijC) that met his team’s criterion for being potentially fine-tuning (having the same point mutation selected at least twice in different replicate strains) could also be selected if they suffered loss-of-function mutations, indicating that degrading the protein’s activity was beneficial. Another protein (spoT) suffered multiple different mutations, likely indicating it was being damaged at various points (which of course is much easier to do than to improve a protein). Several of the other proteins (atoC, hflB, infC, rpsD) acquired single amino acid substitutions that, I do agree, may be “fine-tuning” the proteins in the sense of marginally adjusting them to the conditions of the LTEE. However, they also nicely illustrate the difficulty of doing so, since they took tens of thousands of generations to appear, far longer than beneficial degradative mutations in other genes.
Thus, at the end of scores of thousands of generations, there is some hope that perhaps 4 of 57 beneficial mutations — fewer than 10 percent — did not degrade their respective genes. As I wrote in Darwin Devolves, “Darwin’s mechanism works chiefly by squandering genetic information for short-term gain.”
The Ant and the Grasshopper
One final, ominous point. The paper Lenski is referring to above is titled “Core Genes Evolve Rapidly in the Long-Term Evolution Experiment with Escherichia coli.” The Abstract reads in part:
We asked whether the same genes that evolve rapidly in the long-term evolution experiment (LTEE) with Escherichia coli have also diversified extensively in nature. To make this comparison, we identified ∼2000 core genes shared among 60 E. coli strains. During the LTEE, core genes accumulated significantly more nonsynonymous mutations than flexible (i.e., noncore) genes. Furthermore, core genes under positive selection in the LTEE are more conserved in nature than the average core gene.
In other words, random mutation will just as mindlessly throw away even core genes (presumably more useful under more circumstances) than noncore genes, if that affords momentary advantage. There is no planning for or anticipating the future in Darwinism. As in the fable of the ant and the grasshopper, Darwin’s mechanism is clearly the grasshopper.
In Grateful Recognition
Anyone who is interested in the topic of evolution should feel very grateful to Richard Lenski and his lab. Because of their work we can discuss the implications of real, relevant facts, rather than of unanchored speculations.