University of California evolutionary biologist John Avise has penned a book, Inside the Human Genome: A Case for Non-Intelligent Design, and gotten it published by a top academic publishing house, Oxford University Press. Avise, a member of the National Academy of Sciences, has for decades been a leading researcher in evolutionary and ecological genetics. He has written hundreds of research articles and over a dozen books. Clearly he has an impressive scientific mind.

Which makes it all the more astonishing that his new book shows all the intellectual savvy of a typical late-night college dormroom bull session. As his subtitle announces, Avise is anxious to show that, despite the claims of certain renegade biochemists, the molecular features of the human genome discovered by science in the recent past show no traces of intelligent design. They are chaotic, haphazard, a mess. Any designer with the smarts of at least, oh, say, John Avise, would have done a much better job.

Avise tries to steal three bases on a bunt. He claims that both [Darwinian] evolution and intelligent design can explain the functional parts of the genome, but only evolution can explain the dysfunctional parts (because a beneficent God would not have made those). So he points to what he deems to be poor design and, voila!, that proves the most intricate, functional molecular machines arose by random mutation and natural selection. No actual separate demonstration of that is thought necessary. In fact, Avise makes only the most cursory attempt to address the scientific argument for ID. His chapter 5 is in large part devoted to answering (after a fashion) my Darwin’s Black Box. Yet in the chapter Avise’s only attempt to explain one of my book’s examples of irreducible complexity is to cite Liu and Ochman’s (2007) dubious endeavor to tag all bacterial flagellar genes as descendants of one amazing prodigy gene. The rest of the chapter is pretty much hand waving.

Avise’s main theme is that genes can break, leading to genetic diseases. He has a figure outlining human chromosome 2 and the regions of this chromosome to which various diseases map, such as abetalipoproteinemia and Waardenburg syndrome. A nearby table lists genetic metabolic diseases compiled in Mendelian Inheritance in Man. His whole argument can pretty much be summed up in one brief quote: “Lesch-Nyhan syndrome hardly seems like the kind of outcome that would be countenanced by a loving all-powerful Diety [sic].” (p. 64) In other words, the theological argument from evil — the same argument Darwin gave when he proclaimed that no beneficent God would allow wasp larvae to feed on the living bodies of caterpillars.

Well, it does not follow that, because the parts of my car can break, the car was not designed. Nor does it follow that the Ford motor company is evil. Of course Avise is making a brief against a “loving all-powerful” entity, which does not describe Ford. Yet, beginning with the Book of Job, throughout history philosophers and theologians have wrestled with the problem of evil. I’m no theologian, so I can’t rigorously evaluate those arguments. But Avise is no theologian either and, despite writing an entire book that revolves around the problem of evil, he doesn’t even attempt to engage those philosophical arguments.

The bottom line is, if you’re the kind of person who thinks that because some people smell bad due to a certain genetic disease (trimethylaminuria, p. 64) it follows that Darwinian processes made the eye, this is the book for you. Other folks will conclude that the academic standards of Oxford University Press have slipped a few notches.

Reference

Liu,R. and Ochman,H. 2007. Stepwise formation of the bacterial flagellar system. Proc. Natl. Acad. Sci. U. S. A 104:7116-7121.

The science writer Carl Zimmer posted an invited replyhttp://tinyurl.com/yhpm3t7 on his blog from Joseph Thornton of the University of Oregon to my recent comments about Thornton’s work. This is the last of four posts addressing it. References appear at the bottom of this post.

At the end of his post Thornton waxes wroth.

Behe’s argument has no scientific merit.  It is based on a misunderstanding of the fundamental processes of molecular evolution and a failure to appreciate the nature of probability itself.  There is no scientific controversy about whether natural processes can drive the evolution of complex proteins.  The work of my research group should not be misintepreted by those who would like to pretend that there is.

Well, now. I’ll leave it to the reader of my previous replies to Thornton to decide whether she thinks they have scientific merit, and whether it is I or he who misunderstands the disputed facets of molecular evolution. As for “the nature of probability itself” and “no scientific controversy”, I will briefly address those here.

To illustrate his own grasp of probability Professor Thornton talks baseball.

[Behe] supposes that if each of a set of specific evolutionary outcomes has a low probability, then none will evolve.  This is like saying that, because the probability was vanishingly small that the 1996 Yankees would finish 92-70 with 871 runs scored and 787 allowed and then win the World Series in six games over Atlanta, the fact that all this occurred means it must have been willed by God.

Let me first say that, as a devout fan of the Philadelphia Phillies, I would never think that a Yankees title was intended by the deity. (Bought by George Steinbrenner, perhaps, but certainly not “willed by God”.) That aside, I don’t think Thornton’s analogy captures the evolutionary problem. The example he chose posits a fully functioning team for a very specific game, baseball, performing within the parameters it was designed to — hitting the ball, playing defense, winning and losing games. Even the 1962 Mets did all those things (in somewhat different proportions). Yet the problem for the steroid receptor proteins Thornton’s lab designed was to work at all. To do so they needed to have the correct tools (the right amino acid residues) oriented in the right directions. So let’s change his example a bit. Instead of asking if the Yankees would have won the title with a different number of runs, let’s ask if they would have won if their batters lay down on the ground instead of standing when at bat. And let’s ask if they would have won if they swung towels instead of wooden bats. And if their pitchers threw the ball in random directions. And if their fielders all huddled together in left field, or ran away from a hit ball instead of towards it. I’ll bet even Professor Thornton would be surprised if they won under those circumstances.

Which of those strange behaviors would the imaginary Yankees have to change to win a Series title? — All of them. And how long would it likely take if each season they randomly changed one behavior a bit (say, fielders ran in a direction 173 degrees from a hit ball instead of 180 degrees straight away from it)? — Very, very long. The bottom line is this: it is Thornton who, frankly, doesn’t understand probability applied to evolutionary possibilities. His set of conceivable examples is severely restricted to ones that simply have to work, or that lead inexorably in the direction he wants them to go, without comprehending that there is no evolutionary law that says anything has to work, or that the best current innovation has to lead along a path to something even better. The remarkable thing is that his own admirable laboratory research illustrates this, but he is too enthralled by Darwinian theory to see it.

As for “no scientific controversy”, even a brief excursion into the history of science shows many uncontroversial, widely-accepted theories that were in fact wrong. There was no scientific controversy in the 19^th century about the existence of the ether, or the adequacy of Newton’s laws. And, if one relies on science journals for her entire perspective, there is no controversy today about whether undirected natural processes can account for the origin of life. Yet neither can any scientist today detail a plausible theory of the origin of life. So the bare question of whether some idea is or is not controversial within the scientific community is itself simply a sociological question, not a scientific one. And when the idea is defended so weakly by someone as intelligent as Professor Thornton, it would seem that sociology is pretty much all the idea has going for it.

References

1. Bridgham, J.T., Ortlund, E.A., and Thornton, J.W. 2009. An epistatic ratchet constrains the direction of glucocorticoid receptor evolution.Nature 461:515-519. http://tinyurl.com/yj582bm
2. Bridgham, J.T., Carroll, S.M., and Thornton, J.W. 2006. Evolution of hormone-receptor complexity by molecular exploitation. Science312:97-101. http://tinyurl.com/yfkcwpr
3. Ohno, S. 1970. Evolution by gene duplication. Springer-Verlag, Berlin, Germany.
4. Behe, M.J. and Snoke, D.W. 2004. Simulating evolution by gene duplication of protein features that require multiple amino acid residues. Protein Sci. 13:2651-2664. http://tinyurl.com/yjngprl

The science writer Carl Zimmer posted an invited replyhttp://tinyurl.com/yhpm3t7 on his blog from Joseph Thornton of the University of Oregon to my recent comments about Thornton’s work. This is the third of several posts addressing it. References will appear in the last post.

Now back to Thornton’s first point, the role of neutral mutations (which he sometimes labels “permissive” mutations). At several places in his post Thornton implies I’m unaware of the possibilities opened up by genetic drift:

“Behe’s discussion of our 2009 paper in Nature is a gross misreading because it ignores the importance of neutral pathways in protein evolution…. Behe’s first error is to ignore the fact that adaptive combinations of mutations can and do evolve by pathways involving neutral intermediates…. As Fig. 4 in our paper shows, there are several pathways back to the ancestral sequence that pass only through steps that are neutral or beneficial with respect to the protein’s functions.”

My interest in evolution by neutral mutation, however, is a matter of public record. It is an old idea that if a gene for a protein duplicates (3), then multiple mutations can accumulate in a neutral fashion in the “spare” gene copy, even if those mutations would be severely deleterious if they occurred in a single-copy gene. Four years ago David Snoke and I wrote a paper entitled “Simulating evolution by gene duplication of protein features that require multiple amino acid residues” (4) where we investigated aspects of that scenario. The bottom line is that, although by assumption of the model anything is possible, when evolution must pass through multiple neutral steps the wind goes out of Darwinian sails, and a drifting voyage can take a very, very long time indeed. But don’t just take my word for it — listen to Professor Thornton (1):

“To restore the ancestral conformation by reversing group X, the restrictive effect of the substitutions in group W must first be reversed, as must group Y. Reversal to w and y in the absence of x, however,does nothing to enhance the ancestral function; in most contexts, reversing these mutations substantially impairs both the ancestral and derived functions. Furthermore, the permissive effect of reversing four of the mutations in group W requires pairs of substitutions at interacting sites. Selection for the ancestral function would therefore not be sufficient to drive AncGR2 back to the ancestral states of w and x, because passage through deleterious and/or neutral intermediates would be required; the probability of each required substitution would be low, and the probability of all in combination would be virtually zero.” (my emphasis)

Let’s quote that last sentence again, with emphasis: “Selection for the ancestral function would therefore not be sufficient … because passage through deleterious and/or neutral intermediates would be required; the probability of each required substitution would be low, and the probability of all in combination would be virtually zero.” If Thornton himself discounts the power of genetic drift when it suits him, why shouldn’t I?

In his blog response to me Professor Thornton wants to emphasize that selection-plus-drift can sometimes lead from one nearby function to another, as it did in his work on the ancestral MR-like to the GR-like receptor transition. (2) But I and virtually everyone else already thought that was true. That’s why at the time I called those results (perhaps impolitely, but accurately) “piddling”. A surprise it was not. In his 2009 paper investigating the reverse transition, however, Thornton wants to emphasize (because it is unexpected) that in some cases selection-plus-drift can not lead (with anything like reasonable probability) even to a very similar function. Now that was surprising to me and apparently to many other folks.

The immediate, obvious implication (which he clearly wants to keep far away from) is that the 2009 results render problematic even pretty small changes in structure/function for all proteins — not just the ones he worked on. (Thornton himself is betting on this: “We predict that future investigations, like ours, will support a molecular version of Dollo’s law: as evolution proceeds, shifts in protein structure-function relations become increasingly difficult to reverse whenever those shifts have complex architectures….”) (1) So how, other than begging the question, are we now to know that even the small differences we see in related protein systems came about by random mutation/selection (and, yes, drift)? Quite simply, we can’t. Yet if even small changes are problematic, then larger changes will be prohibitive, and very big changes essentially unattainable. Thanks to Thornton’s impressive work, we can now see that the limits to Darwinian evolution are more severe than even Ihad supposed.

The science writer Carl Zimmer posted an invited replyhttp://tinyurl.com/yhpm3t7 on his blog from Joseph Thornton of the University of Oregon to my recent comments about Thornton’s work. This is the first of several posts addressing it. References will appear in the last post.

I must say, it never ceases to amaze me how otherwise-very-smart folks like Zimmer and Thornton fail to grasp pretty simple points when it comes to problems for Darwinian mechanisms. Let me start slowly with a petty complaint in Carl Zimmer’s intro to the post. Zimmer is annoyed that I think Thornton’s latest work is “great”, yet I thought his previous work published a few years ago was “piddling”. “Why the change of heart?”, wonders Zimmer.

It’s really not that hard to understand. Here’s a little analogy to illustrate. Suppose some company claimed they could build a super-crane (tip of the hat to Daniel Dennett) which could hoist a whole mountain using a novel technology. Though untested, the great majority of the relevant engineering community was serenely confident it would work as advertised. In a carefully-devised, initial, “proof-of-principle” experiment, a laboratory at the University of Oregon demonstrated that the crane-technology could lift a smooth pebble. The work was published in Science, accompanied by a breathless editorial and a story in the New York Times. In a subsequent careful study published several years later in Nature, however, the same lab unexpectedly showed that if a pebble were even somewhat rough, the crane-technology would not lift it. Since mountains tend to be rough, too, if a super-crane wouldn’t move a rough pebble, then it certainly wouldn’t lift a mountain.

Of course, the initial work, although technically well-done, can fairly be called “piddling” compared to the promised capacity of the crane. The subsequent work, again technically well-done, was “great” because it demonstrated formidable difficulties for the technology at a very basic level that no one — not even (ahem…) the few skeptics — had expected. (I hate to be so pedantic, but unfortunately it seems necessary on this topic.)

A new paper from Richard Lenski’s group has appeared in Nature http://tinyurl.com/ygtcflq and has garnered a fair amount of press attention (for example, herehttp://tinyurl.com/yh7nqht ). Some people asked me for my thoughts about it.

The new paper continues the grand experiment that Lenski has been publishing about lo these many years — allowing a culture of the bacterium E. coli to continuously grow and evolve under his close observation. The only really new thing reported is a technical improvement — these days one can have the entire genome of E. coli “re-sequenced” (that is, determine the sequence of the entire DNA of the particular E. coli you’re working with) done for an affordable cost. (There are companies which will do it for a fee.) So Lenski and collaborators had the whole genomes — each and every nucleotide — sequenced of the E. coli that they have been growing for the past twenty years. Since they froze away portions of their bacterial culture at different times along the way, they now have the exact sequences of the evolving culture at many time points, from inception to 2000 generations to 10,000 to 40,000. Thus they can know exactly which mutations appeared when — an almost-complete paper trail. Very very cool!

From that information they identify a couple score of mutations which they say are likely beneficial ones. That is almost certainly true, but what they don’t emphasize is that many of the beneficial mutations are degradative — that is, they eliminate a gene or its protein’s function. About half of the mutations they initially identified in previous work, but some they report here for the first time. They don’t discuss what the new ones do (they may not yet know), but odds are high that most of them also are degradative, causing proteins either to stop working or to work less well. In any event, there is no indication that any of these are on their way to building some complex new system.

Interestingly, in this paper they report that the E. colistrain became a “mutator”. That means it lost at least some of its ability to repair its DNA, so mutations are accumulating now at a rate about seventy times faster than normal. Lenski had reportedhttp://tinyurl.com/yge8dx4 years earlier that a number of other lines of the evolving population (they started with 12 separate cultures) had become mutators, too. So it seems that loss of ability to repair DNA is a common occurrence under these conditions.

Lenski is a very good self-promoter (no criticism intended; that’s a good thing — scientists have to interest other people in their work), and he always accentuates the positive. So if a gene is blasted to bits by a mutation, he talks cheerfully about how it is a beneficial change that helps the bacterium grow faster. One has to dig hard into the data to see that the bacterium is losing genetic info. In press coverage for this paper, he avows a “new dynamic relationship was established” in the bacterium’s evolution, and one has to read the details of the paper to find out that this is due to a degradative mutation that compromises its normal ability to repair its DNA.

Despite his understandable desire to spin the results his way, Lenski’s decades-long work lines up wonderfully with what an ID person would expect — in a huge number of tries, one sees minor changes, mostly degradative, and no new complex systems. So much for the power of random mutation and natural selection. For his work in this area we should be very grateful. It gives us solid results to point to, rather than having to debate speculative scenarios.

References

Barrick, J.E., Yu, D.S., Yoon, S.H., Jeong, H., Oh, T.K., Schneider, D., Lenski, R.E., and Kim,J.F. 2009. Genome evolution and adaptation in a long-term experiment with Escherichia coli. Nature, doi:10.1038/nature08480.

Sniegowski, P.D., Gerrish, P.J., and Lenski, R.E. 1997. Evolution of high mutation rates in experimental populations of E. coli. Nature 387:703-705

Nature has recently published an interesting paper which places severe limits on Darwinian evolution. The manuscript, from the laboratory of Joseph Thornton at the University of Oregon, is entitled “An epistatic ratchet constrains the direction of glucocorticoid receptor evolution”. ( http://tinyurl.com/yeq2cy8 ) The work is interpreted by its authors within a standard Darwinian framework, but the results line up very well with arguments I made in The Edge of Evolution. ( http://tinyurl.com/yba6vba ) This is the last of three posts discussing it.

Bridgham et al (2009) are interested in the reversibility of evolution, and discuss their results in terms of something called “Dollo’s law.” Louis Dollo, an early 20^thcentury paleobiologist, was interested in discerning phylogenies. He maintained that one could always distinguish ancestral forms from descendant forms. Stephen Jay Gould (1970) commented that Dollo’s “law” was not an empirical observation, but rather a postulate which he felt was necessary to properly construct phylogenies. Over the years the meaning of “Dollo’s law” transmogrified. In modern usage, the phrase has come to mean that complex traits, once lost, do not re-evolve in the same lineage. For example, whales do not re-evolve gills, even though they are aquatic creatures who descended from fish, because gills are a lost, complex trait in that lineage.

Dollo’s law is taken with a grain of salt by many biologists, and apparent exceptions to the law have been noted (cited in Bridgham et al 2009). Nonetheless, although Dollo’s law isn’t very reliable at the organismal level, maybe it can do better at the molecular level. Bridgham et al (2009) wanted to test that idea:

Evolutionary reversibility represents a strong test of the importance of contingency and determinism in evolution. If selection is limited in its ability to drive the reacquisition of ancestral forms, then the future outcomes available to evolution at any point in time must depend strongly on the present state and, in turn, on the past. Ready reversibility, in contrast, would indicate that natural selection can produce the same optimal form in any given environment, irrespective of history. The evolutionary reversibility of a protein can be evaluated at three levels: molecular sequence, protein function, and the structural/mechanistic underpinnings for that function. The latter is most relevant to understanding the roles of contingency and determinism in evolution. … True reversal, involving restoration of the ancestral phenotype by the ancestral structure-function relations, would indicate that the forms of functional proteins can evolve deterministically, irrespective of contingent historical events.

After experimentally supporting the claim that a GR-like protein would be very unlikely to revert to an MR-like ancestral form by Darwinian means, they concluded:

We predict that future investigations, like ours, will support a molecular version of Dollo’s law: as evolution proceeds, shifts in protein structure-function relations become increasingly difficult to reverse whenever those shifts have complex architectures, such as requiring conformational changes or epistatically interacting substitutions.

I think the experimental work of Bridgham et al (2009) is great, and I think their interpretive reasoning is fine as far as it goes. But it is severely pinched by their Darwinian framework; their results point to much more.

Just as for some general laws of physics, there is nothing inherently time-asymmetric about generic random mutation and selection. So there should be nothing particularly special about evolving back in history versus forward. The only thing that would be “special” about going back is that you can (potentially) know which way you had come, so you can see if the steps can be retraced, as Bridgham et al (2009) did. However, the huge roadblock that the authors discovered for one homologous protein converting to another by Darwinian processes did not have to be in the past — the roadblock could as easily have been in the future. If the GR-like protein had come first in history, then no MR-like protein would likely have arisen by Darwinian means. In that case, however, there would have been no question even raised by investigators about the reversibility of that evolutionary path, because the “path” would not exist — it would have been blocked at the start, in the forward direction. Questions do not arise about hypothetical pathways that would have to pass through brick walls.

The old, organismal, time-asymmetric Dollo’s law supposedly blocked off just the past to Darwinian processes, for arbitrary reasons. A Dollo’s law in the molecular sense of Bridgham et al (2009), however, is time-symmetric.  A time-symmetric law will substantially block both the past and the future, for well-understood reasons: Natural selection fits a protein to a current, not any future (nor any previous), task; thus it tends strongly to restrict other potential structures/functions.  The very same considerations (“shifts in protein structure-function relations”, “epistatically interacting substitutions”, and so on) that frustrate the reacquisition of complex molecular features will tend strongly to stymie their acquisition in the first place, because no potential protein component would ever be without a prior history of selection. A time-symmetric Dollo’s law turns the notion of “pre-adaptation” on its head. The law instead predicts something like “pre-sequestration”, where proteins that are currently being used for one complex purpose are very unlikely to be available for either reversion to past functions or future alternative uses.

Yet here we are, with complex life all around us and in us. If a time-symmetric Dollo’s law were really such a big roadblock, how did life come to be? Here is where their Darwinian framework most seriously blinkers their vision. Bridgham et al (2009) aimed to test “the importance of contingency and determinism in evolution”. But chance and necessity are not the only things that exist. There are also mind and plan. In fact, in their own work the authors themselves reconstructed the ancestral protein from the descendant protein, easily overcoming the hurdle that they realized would block a Darwinian process. Their own minds directed events that chance and necessity never could.

References

Bridgham,J.T., Ortlund,E.A., and Thornton,J.W. 2009. An epistatic ratchet constrains the direction of glucocorticoid receptor evolution. Nature 461:515-519.

Bridgham,J.T., Carroll,S.M., and Thornton,J.W. 2006. Evolution of hormone-receptor complexity by molecular exploitation. Science 312:97-101.

Gould,S.J. 1970. Dollo on Dollo’s law: irreversibility and the status of evolutionary laws. J. Hist. Biol. 3:189-212.

Nature has recently published an interesting paper which places severe limits on Darwinian evolution. The manuscript, from the laboratory of Joseph Thornton at the University of Oregon, is entitled “An epistatic ratchet constrains the direction of glucocorticoid receptor evolution”. ( http://tinyurl.com/yeq2cy8 ) The work is interpreted by its authors within a standard Darwinian framework, but the results line up very well with arguments I made in The Edge of Evolution. ( http://tinyurl.com/yba6vba )This is the second of several posts discussing it.

Using clever synthetic and analytical techniques, Bridgham et al (2009) show that the more recent hormone receptor protein that they synthesized, a GR-like protein, can’t easily revert to the ancestral structure and activity of an MR-like protein because its structure has been adjusted by selection to its present evolutionary task, and multiple amino acid changes would be needed to switch it back. That is a very general, extremely important point that deserves much more emphasis. In all cases — not just this one — natural selection is expected to hone a protein to suit its current activity, not to suit some future, alternate function. And that is a very strong reason why we should not expect a protein performing one function in a cell to easily be able to evolve another, different function by Darwinian means. In fact, the great work of Bridgham et al (2009) shows that it may not be do-able for Darwinian processes even to produce a protein performing a function very similar to that of a homologous protein.

Before reading their paper even I would have happily conceded for the sake of argument that random mutation plus selection could convert an MR-like protein to a GR-like protein and back again, as many times as necessary. Now, thanks to the work of Bridgham et al (2009), even such apparently minor switches in structure and function are shown to be quite problematic. It seems Darwinian processes can’t manage to do even as much as I had thought.

(As an aside into the circus world of popular-level debates on Darwinism, the work of Bridgham et al (2009) nicely shows the fallacy of the anti-ID retort that, say, a mousetrap is not irreducibly complex because, if the catch and holding bar are removed, parts of it can still be used as a tie clip. The same principle that holds for cellular machinery would hold for all machinery. Something that was shaped by selection to work as a tie clip would not look like an ancestor of a mousetrap, or easily be converted to one by random changes plus selection. If you look at images of tie clips on the internet, none of them resemble mousetraps — except for those purposely designed by folks who were arguing against irreducible complexity.)

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.

The bottom line is that, for a given evolutionary task, at best only a handful of proteins will likely be helpful to evolve, at worst none may help. To calculate the probability of, say, a helpful protein-protein interaction developing in response to any particular selective pressure, it’s mistaken to gratuitously multiply odds by the total number of proteins in a cell. Combined with the point made by Bridgham et al (2009), that even tiny structural/functional changes may not be achievable by random mutation/ selection, these considerations pretty much squelch the likelihood of Darwinian processes doing much of significance during evolution.

References

Bridgham,J.T., Ortlund,E.A., and Thornton,J.W. 2009. An epistatic ratchet constrains the direction of glucocorticoid receptor evolution. Nature 461:515-519.

Bridgham,J.T., Carroll,S.M., and Thornton,J.W. 2006. Evolution of hormone-receptor complexity by molecular exploitation. Science 312:97-101.

Nature has published an interesting paper recently which places severe limits on Darwinian evolution. This is the first of several posts discussing it.

The manuscript, from the laboratory of Joseph Thornton at the University of Oregon, is entitled “An epistatic ratchet constrains the direction of glucocorticoid receptor evolution”. ( http://tinyurl.com/yeq2cy8 ) The work is interpreted by its authors within a standard Darwinian framework. Nonetheless, like the important work over the years of Michigan State’s Richard Lenski on laboratory evolution of E. coli, which has shown trillions of bacteria evolving under selection for tens of thousands of generations yielding just broken genes and minor changes, the new work demonstrates the looming brick wall which confronts unguided evolution in at least one system. And it points strongly to the conclusion that such walls are common throughout all of biology.

In the paper Bridgham et al (2009) continue their earlier work on steroid hormone receptor evolution. Previously they had constructed in the laboratory a protein which they inferred to be the ancestral sequence of two modern hormone receptors abbreviated GR and MR (Bridgham et al 2006). They then showed that if they changed two amino acid residues in the inferred ancestral receptor protein into ones which occur in GR, they could change its binding specificity somewhat in the direction of modern GR’s specificity. (All the work was done on molecules in the laboratory. No measurements were made of the selective value of the changes in real organisms in nature. Thus any relevance to actual biology is speculative.) They surmised that a gene duplication plus sequence diversification could have given rise to MR and GR. As I wrote in a comment at the time ( http://www.discovery.org/a/3415 ), that was interesting work, and the conclusion was reasonable, but the result was exceedingly modest and well within the boundaries that an intelligent design proponent like myself would ascribe to Darwinian processes. After all, the starting point was a protein which binds several steroid hormones, and the ending point was a slightly different protein that binds the same steroid hormones with slightly different strengths. How hard could that be?

Well, it turns out that Darwinian evolution can have a lot of trouble accomplishing even that simple task, or at least its opposite. In the new paper the authors try the reverse experiment. They begin with the more modern hormone receptor (which is more restrictive in the steroids it binds) and ask whether a Darwinian process could get the ancestral activity back (which is more permissive). Their answer is no, it couldn’t. They show that a handful of amino acid residues in the more recent receptor would first have to be changed before it could act as the ancestral form is supposed to have done, and that is very unlikely to occur. In other words, the new starting point is also a protein which binds a steroid hormone, and the new desired ending point is also a slightly different protein that binds steroid hormones. How hard could that be? But it turns out that Darwinian processes can’t reach it, because several amino acids would have to be altered before the target activity kicked in.

A number of points can be drawn from this fine work:

• The central point of The Edge of Evolution was tat if several amino acids of a protein must be changed before a certain selective effect is available, then that is effectively beyond the reach of Darwinian processes. Bridgham et al (2009) confirm that conclusion. (As an aside, it would make a good project for a sociologist of science to ask why the same conclusion is met with howls of protest when presented by a Darwinian skeptic such as myself, but garners praise when presented by someone else.)
• There is no reason to think the protein studied by Bridgham et al (2009) is unusual in its difficulty of developing a binding site for even a relatively closely-related substance. In fact, in the absence of strong opposing data, that should be the default, reasonable assumption.
• That same reasonable assumption counts strongly against any two unrelated proteins easily developing a binding site for each other.
• That reasonable assumption therefore negates all woolly Darwinian evolutionary scenarios where critical protein binding sites are assumed without justification to pop up when needed (such as, say, in the building of multiprotein structures like the cilium or flagellum).
• Thus the work strongly supports the conclusion of Edge that Darwinian processes are highly unlikely to have built the complex molecular machinery of the cell.

References

Bridgham,J.T., Ortlund,E.A., and Thornton,J.W. 2009. An epistatic ratchet constrains the direction of glucocorticoid receptor evolution. Nature 461:515-519.

Bridgham,J.T., Carroll,S.M., and Thornton,J.W. 2006. Evolution of hormone-receptor complexity by molecular exploitation. Science 312:97-101.

In a new segment, http://bloggingheads.tv/diavlogs/22300 , Bloggingheads chief Robert Wright and Bloggingheads correspondent George Johnson go on for 75 minutes about the trauma of a pair of heretics (me and Paul Nelson, on separate segments) appearing on their site. I would urge everyone who doesn’t have pressing matters to attend to, such as the need to wash your hair, to tune in for the full time. It’s really fascinating in its way to see two grown men in such a hand-wringing lather. It’s also fascinating to see that neither of them in 75 minutes offers a reason for the correctness of their own views, or the wrongness of ours. The closest they come is when George Johnson invokes the hoary “methodological naturalism.”

One little segment was particularly rich. Johnson is faint with indignation that, in a post commenting on Bloggingheads originally pulling my interview with John McWhorter, I put up the well-known picture of Joseph Stalin standing with a group of people and a second photo in which one poor bloke’s image had been removed. Why, lamented Johnson, I was comparing poor Bloggingheads to a murderous regime! These ID folks revel in their supposed persecution!

In that post my only remark concerning the picture (which appeared at the end) was “Below is a time-lapse picture of my Bloggingheads interview. I’m the guy on the right.” (That is, the fellow who had disappeared.) Now, it may be that George Johnson has never heard the phrase “tongue-in-cheek”; if so he should look it up. Otherwise he may be confused that the guy on the right actually doesn’t look like me, and that the interview wasn’t really filmed next to a Russian river. Interestingly, at one point when he was explaining why he had the interview put back up, Robert Wright said that if you take down an interview that had been put up, why, it looks “like you’re trying to re-write history.” Well, now, what picture might someone post if he was trying to illustrate Wright’s astute point?