An experimental evolutionist replies to Behe

My colleague Jim Bull at the University of Texas at Austin conducted several of the phage experiments that creationist Michael Behe mentions in his recent Quarterly Review of Biology paper on experimental evolution.  As you may recall, Behe reviewed short-term studies of adaptive evolution of bacteria and viruses in the laboratory, and concluded that nearly all of this adaptation resulted from either inactivation of genes or the accumulation of small changes in genes (e.g. single nucleotide substitutions in the DNA) that caused a quantitative but not qualitative change in gene activity.

Behe’s implicit conclusion was that evolution in nature—and not just in bacteria and viruses, but all species—also occurred in this way; that is, brand-new genes or genetic elements (he calls them “FCTs”) could not originate de novo by mutation and natural selection, but had to be put there by the Intelligent Designer (aka God/Jebus).  Behe did not, and could not, say this in the paper, but intelligent-design advocates certainly touted this conclusion (see here and here, for instance), and now Behe himself has said the same thing on his blog at Uncommon Descent:

. . . I was saying that, no matter what causes gain-of-FCT events to sporadically arise in nature (and I of course think the more complex ones likely resulted from deliberate intelligent design http://tinyurl.com/32n64xl), short-term Darwinian evolution will be dominated by loss-of-FCT, which is itself an important, basic fact about the tempo of evolution.

Note that here he doesn‘t limit this conclusion (which he conveniently omitted from the QRB paper) to bacteria and viruses.

I’ve criticized Behe’s paper because in nearly all the laboratory experiments the researchers deliberately left out an important source of new genes and genetic elements that applies to bacteria and viruses in nature: the uptake of DNA (via “horizontal transmission”) from other species.  The experiments reviewed by Behe. then, weren’t a good model of what would happen to evolving microbes in nature, which are in fact often known to absorb new genes from distantly-related species. Further, in eukaryotes (organisms with “true cells”) we know that evolution has involved the creation of new genes and gene-controlling regions via gene duplication and divergence. (I’ll post more on this later today).  Thus, while Behe’s conclusions are valid for his particular, limited group of laboratory studies, they simply can’t be extended willy-nilly to evolution in nature.

I sent Behe’s paper to Jim Bull (who had already read it in draft) along with my replies, and asked him to comment.  Here, for the record, is his response.  This is somewhat technical, but will be useful to those who have read Behe’s paper, and I thought it deserved to be posted for the scientific record.  (Terminology: “phages” are short for “bacteriophages,” and refer to those viruses that infect bacteria.)

I’ve been asked to comment here on the paper by Michael Behe (MB), in large part because it reviews work of mine and because it is the focus of some controversy.  I read the paper in draft form some months ago and have not re-read it, but even then it exhibited an impressive command of the experimental evolution literature, at least the literature on adaptation of whole genomes of bacteria and phages (as opposed to the ‘directed’ evolution of genes on plasmids and of naked nucleic acids).

I consider MB’s characterization of most molecular evolution in these experiments as point mutations and/or deletions to be accurate.  Indeed, as I told MB in my comments on his ms, I had made the same point in a recent book chapter.  We have not seen the evolution of much novelty in these lab experiments on bacteria and viruses, at least not the classic gene duplication followed by diversification into new functions.  There is, however, a literature on what is known as directed evolution that does document the evolution of novelty when strong selection is applied to large populations, but those studies focus on individual genes (e.g., on plasmids) or short nucleic acids (e.g., 50-base RNA molecules).

What surprises me is that anyone would consider this absence of novelty in experimental evolution studies to be surprising, given what we know both about evolution and about the nature of the experiments.  As Jerry Coyne (JC) commented recently, the organisms and conditions used for those studies are not amenable to many of the types of evolutionary mechanisms and selective conditions that we think operate in nature.  The natural environment for many microbes includes lots of  free ‘environmental’ DNA from many sources, produced when cells die and release their DNA.  In addition, phages abound in natural environments, providing a ready means of DNA transfer between different bacteria, but many bacteria are also capable of incorporating environmental DNA into their genomes.

Finally, selection is not spatially uniform in nature, so that different individuals of the same population can be exposed to a wide variety of selective conditions.  In contrast, Rich Lenski’s famous lines use a single strain of E. coli in minimal media, transfered daily to fresh media.  No phage or other species of bacteria are present.  That E. coli strain is not capable of taking up DNA from the environment (which is irrelevant in these experiments anyway, since the only DNA in that environment would be from other E, coli of the same population).

Likewise, the phages used for most of the experimental work do not easily incorporate foreign DNA.  (MB used one of my studies with T7 to criticize JC for making this claim, but even here there’s a problem: what we failed to point out in our paper, and is fatal to MB’s criticism, is the fact that T7 degrades E. coli DNA, so even if the phage did incorporate an E coli gene, it might well destroy itself in the next infection.)  Other phages used in experimental evolution studies likewise are not known to incoeporate or tolerate host DNA or RNA, with the exception of M13.

Some experiments have attempted to select new functions and shown limited success.  One by Ichiro Matsumura selected the E. coli gene encoding beta glucoronidase to degrade a different substrate (a beta galactoside).  With strong selection over several cycles, he obtained a 500-fold gain in enzyme activity on the new substrate, but it was still not enough activity to allow the bacterium to grow on that substrate.  Four point mutations were responsible for the change in activity.  This study (and there are no doubt many parallels in the directed evolution  literature) suggests that evolution of new function from an old function likely is a slow process under more natural circumstances and requires a delicate combination of environmental conditions affecting selection.  Matsumura’s result certainly supports the possibility of evolution of new function from old function, but the design did not allow divergence between two identical copies—only one copy was present in the cell.

A study by Alisha Holloway, Tim Palzkill and me attempted to select the divergence between two copies of a bacterial gene.  Two identical copies of the gene for degrading ampicillin – Bla (for beta lactamase) – were put into the same cell, each on their own plasmid, and divergence was favored by growing the bacteria on two different antibiotics (ampicillin and a cephalosporin).  This seemed to be a sure-fire way to evolve divergent functions and maintain both copies, because of two observations already published.  First, although the initial Bla could not degrade the cephalosporin, it could evolve to resist the cephalosporin with one or two point mutations.   Second, resistance to the cephalosporing came at some cost in the ability of the mutated gene to resist ampicillin.  In principle, therefore, the only way for the cell to tolerate the two drugs was to maintain one copy of Bla unaltered and evolve the other copy to resist the cephalosporin.   Yet although cephalosporin resistance evolved in one of the two copies of Bla, the other copy of Bla was still lost — the cephalosporin resistant gene still had enough resistance to amp to allow the bacteria to grow.  This study merely illustrates that the conditions favoring the maintenance of two copies undergoing evolutionary divergence are delicate.  If we had 30 examples of these kinds of studies, and all gave negative results, we might begin to question the ‘duplication-then-divergence’ model.  But we already have plenty of evidence that new functions can evolve from old (e.g., the Matsumura study, and even the evolution of cephalosporin resistance from Bla); where we don’t have much effort yet is laboratory studies of divergence between two copies of what used to be the same gene.

My own view of the MB paper is that it has done a service to the study of evolution by pointing out where the next generation of experients should focus.  We don’t yet have many studies on the long term evolution of protein novelty (to get extreme divergence), and the types of selection used are typically extreme.  Answers to these problems aren’t yet available simply because we simply have not applied much effort.  Indeed, there is still much we have yet to understand about the seemingly more mundane process of point mutation evolution in the simplest environments.  As I noted above, we do have many dozens of ‘directed evolution” studies in which various functions and activities haven been evolved from random libraries of RNA molecules, and those studies have shown that selection can be a powerful and creative force.

A h/t to Dr. Bull for providing this response.  Here’s a photo of him guarding his property, the Double Helix Ranch in Texas, where he and co-owner David Hillis breed longhorn cattle:

15 Comments

  1. NewEnglandBob
    Posted December 20, 2010 at 7:58 am | Permalink

    Terrific analysis with suggestions for future research. Thanks for sharing this.

  2. Insightful Ape
    Posted December 20, 2010 at 8:56 am | Permalink

    So where is young earth creationist Paul Nelson when you need him? He was looking for an article showing a mutation leading to gain of function.

  3. Ken Pidcock
    Posted December 20, 2010 at 9:29 am | Permalink

    Somebody with a good theoretical background should look into the evolution of extended-spectrum β-lactamases, ESBLs. Their bacterial hosts commonly carry multiple copies, from multiple families, on multiple (impressively mobile) plasmids. I’ve often thought that the loosening of selection brought about by this circumstance could be contributing to rapid evolution to carbapenemases, etc.

  4. Sigmund
    Posted December 20, 2010 at 9:44 am | Permalink

    From Behe’s comments on the DI site it appears the article was simple an exercise in finding gaps for them to stuff with Jebus. He clearly meant his article stand as a claim that novel functions arise so rarely in nature as to be unimportant in the evolution of functional elements. It must be very frustrating for Behe, working in a field like biochemistry, knowing that the rate of progress in this area of science means any gaps identified today are unlikely to stay that way for long. He is like a nineteenth century mormon leader, holding up a papyrus scroll and proclaiming it the written words of the Angel Moroni, all the while knowing that the hieroglyphic language on the Rosetta stone is slowly being translated and will, sooner or later, reveal his deception.

    • MadScientist
      Posted December 20, 2010 at 11:33 am | Permalink

      I don’t even see where there can be any gaps. It was simply a matter of “I reviewed lots of previous work done with certain restrictions an in the timelines of all those experiments there were no noted successive additive mutations which resulted in a new function encoding, but functions had been altered due to deletions.” The only conclusion I can come up with is that those experiments would have to be run much longer before anyone might have a chance to observe a new function encoded via successive additive changes to a gene. So the only thing I see of any value in the piece is that additive change in genes, with as many external factors as possible taken out, is very slow. The next step for Behe of course is to say “see, it takes so long that god must have done it or else we would be older than the universe” – but I still don’t see the gap filler there.

  5. Dominic
    Posted December 20, 2010 at 10:01 am | Permalink

    Guarding the ranch from ravenous Jebus lovers no doubt!

    Did anyone see the Bjoern Brembs ‘free will’ in drosophila article in Proceedings of the Royal Society B?
    http://brembs.net/spontaneous/

  6. KP
    Posted December 20, 2010 at 10:08 am | Permalink

    It would be interesting if we could see what the QRB referees said in their comments before the paper was accepted.

    • KP
      Posted December 20, 2010 at 10:12 am | Permalink

      Actually was Bull one of the referees or did he just give a friendly review before submission?

  7. Grendels Dad
    Posted December 20, 2010 at 3:46 pm | Permalink

    I thought the two helix were not supposed to be so symmetrical. Was the 180 degree separation too visually appealing to resist?

  8. Marella
    Posted December 20, 2010 at 5:06 pm | Permalink

    eukaryotes (organisms with “true cells”)

    Um, is this really what you mean? Shouldn’t that be ‘true nuclei’? I mean a bacterial cell is still a cell isn’t it?

  9. Torbjörn Larsson, OM
    Posted December 20, 2010 at 5:16 pm | Permalink

    In the context this Nature paper could be of interest, on mapping the evolutionary history of whole gene families across the three domains of life onto a geological timeline.

    First, the paper generates an explicit account of gene birth, transfer, duplication and loss over time. Fig 1 shows how gene family birth responded to early environmental changes, and how gene transfer and later gene duplications becomes important factors. (The last figure in the supplement details this; gene duplication is apparently important outside eukaryotes in many cases!?)

    I note for the figure and the post here that “The near absence of de novo birth in modern times probably reflects the fact that ORFan gene families (gene families found in only a single genome), which are widespread across all major prokaryotic groups, are not considered in this study. The excess of gene duplications and ORFans in modern genomes suggests that novel genes from both sources experience high turnover.” [My bold.]

    Second, and this is apparently a robust result, the paper finds an “Archaean Expansion” (AE) of the ancestral genome which coincided with a rapid diversification of bacterial lineages. This is a genomic hyperexplosion compared to the “Cambrian explosion” that creationists obsesses with!

    Tentatively this AE is correlated with the oxygenation of the atmosphere.

    [I'm a layman, but I'm not happy with the traditional rooting between the three domains which could explain the little change found before the Eukaryan-Archaean branches (see the supplement). I'm also not happy with the traditional sterane marking eukaryotes timing event which could explain the problems they have to correlate their model clock with a PhyloBayes clock (see the discussion on p 3 in the pdf doc). But the robust AE result is promising IMHO!]

    I wonder if creationists are happy if bacterial expansion overtakes eukaryote expansion as the potentially most drastic diversification event (genomically speaking) seen, a Biological Big Bang bar none.

    • Posted December 21, 2010 at 4:19 am | Permalink

      So, is this a fair summary?

      - Behe has pointed out in his review paper that significant “neutral” evolution has not been experimentally recorded.

      - Directed evolution is, however, experimentally recorded. This generally involves a few point mutations – presumably either in the regulation of already existing genes, or in slight modification to duplicated or idle genes. Since evolution in vivo takes place as a result of environmental pressures, directed evolution is the form in which we should see it take place. However, such processes in lab are “delicate”, and by inference would also be so in vivo.

      - The fact that new genetic material doesn’t appear to arise very often doesn’t matter, as if it arises somewhere else, it might have been absorbed from the environment. I have to say that to me this sounds not much more convincing as an explanation than panspermia – technically possible, but you can’t regress indefinitely, and the process itself is not convincingly explained, and raises more questions.

      The Nature paper seems to kick the actual generation of new genetic material even further out of sight. Of course, if it is placed out of sight, it is even harder to verify or falsify.

      I’m interested that someone without the apparent metaphysical baggage that surrounds the debate is happy to express appreciation for the paper as it was published. Which was presumably why the journal felt happy to publish it….

  10. SteveF
    Posted December 24, 2010 at 6:04 pm | Permalink

    Behe responds in something of a handwaving fashion:

    http://www.evolutionnews.org/2010/12/more_from_jerry_coyne042161.html

  11. will
    Posted March 20, 2012 at 9:21 am | Permalink

    Wow.
    Thanks Jim.
    Will


3 Trackbacks/Pingbacks

  1. [...] new paper; IDers already distorting Behe’s new paper; Casey Luskin distorts Behe’s paper; An experimental evolutionist replies to Behe), so there’s really no need to revisit it, other than to note the reservations I [...]

  2. [...] [...]

  3. [...] with some pointing to Behe’s omission of eukaryotic evolutionary mechanisms, others to his omission of some bacterial evolutionary mechanisms, and others taking a holistic approach to his [...]

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