Something from Nothing Dept.: Can a Divide-and-Conquer Strategy Climb Mt. Improbable?

Darwinian evolution from the most primitive organisms to the most advanced must have produced huge increases in functional information (see 06/12/2003 entry).  Yet finding specific genetic mechanisms for just how DNA succeeded in “climbing Mt. Improbable,” as Richard Dawkins termed it in his book of the same name, has been daunting.  In a recent paper in PNAS,¹ Austin L. Hughes meant to encourage his fellow Darwinists that explaining the origin of new function in proteins has been given a boost by recent findings.  In the body of the article, however, he appears to have conceded more than he affirmed.  He began,

Evolutionary biologists agree that gene duplication has played an important role [intelligent design term] in the history of life on Earth, providing a supply of novel genes that make it possible for organisms to adapt to new environments.  The existence of diverse multigene families, particularly in eukaryotes, provides evidence that numerous events of gene duplication followed by functional diversification have shaped [intelligent design term] genomes as we know them.  But it is less certain how this panoply of new functions actually arises, leaving room for ingenious speculation but not much rigor.  Cases where we can reconstruct with any confidence the evolutionary steps involved in the functional diversification are relatively few. (Emphasis added in all quotes.)

To switch from gloom to hope, he described an investigation by Tocchini-Valentini et al. that examined genes for tRNA endonuclease among three branches of Archaea.  Two of them contained a single gene that combined the functions of stabilization and catalysis, but a third subdivided the functions between two genes.  They feel this is an example of subfunctionalization (see 10/24/2003 entry); i.e., a case of a multi-function gene splitting sometime in evolutionary history into separate genes that carry on the original functions separately.  Hughes was glad to hear about this report, which to him was “particularly welcome as a concrete example of how new protein functions can arise.”  Yet this would seem to be merely a case of rearranging functions rather than originating new ones, i.e., of dividing without necessarily conquering.  Did he provide any examples of new functions arising by this process?
    The rest of article only elaborates on the theme of subfunctionalization.  Hughes presented various theories, by Ohno, Jensen, Orgel and others, about how gene duplication might have shared and diversified functions among ancestral genomes (see 05/15/2005 entry for another recent example).  He talked about “gene sharing,” in which a gene might produce multiple products depending on the context: i.e., an enzyme in one type of cell, but a crystallin in the eye, but this also begs the question about where the genetic information came from.  He speculated about how subfunctionalization might produce better-adapted proteins by the “Babe Ruth effect” – analogous to how the famous baseball player performed better as either a pitcher or outfielder/hitter, but not both simultaneously – yet did not prove that subfunctionalized proteins either contained more information or did a better job.
    What is more revealing in Hughes’ commentary are statements he made about evolutionary theory, evidence and proof.  Coming from someone who accepts evolution without hesitation, these remarks cast doubt on both the methodology and achievement of an evolutionary approach to genetics:

• Oh no:  He discredited the original subfunctionalization hypothesis of Susumi Ohno:
  

  The first hypothesis regarding the origin of new gene function was that of Ohno, who assumed that, after duplication, one gene copy would be entirely redundant and thus freed from all constraint…. There are a number of reasons for doubting this hypothesis  First, as the late Marianne Hughes and I showed in the case of the tetraploid frog Xenopus laevis, duplicate genes are not in general freed from all functional constraint.  Rather, purifying selection [i.e., conservation] acts to eliminate deleterious nonsynonymous (amino acid-altering) mutations even in apparently redundant gene copies.  Furthermore, there are a number of multigene families where there is evidence that positive Darwinian selection has acted to promote amino acid changes in functionally important regions of proteins.  In these families, new function clearly has not arisen as a result of random mutation alone, contrary to the prediction of Ohno’s model.

  In its place, Hughes offered the alternative hypothesis that “both functions are already present before gene duplication.”  This, however, does not explain the origin of the functions, but only their rearrangement.

• Who needs Darwin?  In a paragraph entitled “The Role of Natural Selection,” Hughes started by denying that natural selection had much to do with it:
  

  One theoretically attractive feature of their model of subfunctionalization, as pointed out by Lynch and colleagues, is that it can occur without the need for positive Darwinian selection, which is thought to be relatively rare at the molecular level.

  If daughter genes inherit just one of two functions, he says, “conservative or purifying natural selection will act against any mutation that eliminates function,” while the other fragment might accumulate mutations by genetic drift.  Again, this does not describe the origin of any new functions, but only the preservation of existing information.

• Gimme your best shot:  Hughes surveyed some of the best examples of Darwinian selection at the molecular level, explaining the “Babe Ruth effect.”  Even these, however, overlook the need for new functional information:
  

  On the other hand, some of the best-documented examples of positive Darwinian selection at the molecular level involve functional diversification among members of multigene families…. It may often be as true of molecules as it is of human beings that “a jack of all trades is master of none.”  In such cases, positive selection may actually favor the loss of one function in a bifunctional molecule if a duplicate gene is able to take up the slack.

• Dunno:  Hughes did not suggest that much is known about evolution by gene duplication, if anything; indeed, it cannot be known:
  

  In the case of archaeal tRNA endonucleases, there is no direct evidence whether drift alone gave rise to subfunctionalization or whether positive selection played a role.  These events occurred in the distant past; thus, the most convincing signal of positive selection, an accelerated rate of nonsynonymous nucleotide substitution is not obtainable, being obscured by numerous subsequent neutral changes.  However, the fact that subfunctionalization has occurred twice independently and by different pathways in the same gene family suggests that positive selection may indeed have been involved.  Perhaps, in the high-temperature environments occupied by these archaeal species, there is something less than optimal about the homotetrameric type of tRNA endonuclease, where the same polypeptide does double duty as a catalytic subunit and a spacer.

• Lessons learned:  Near the end of the article, Hughes made a remarkable admission about the predictive power of Darwinian biology.  He also makes his first mention of a mechanism for new function, but prefaces it with the word perhaps:
  

  If we have learned anything at all in a century and a half of evolutionary biology, it is that facile generalizations are dangerous.  The evolutionary process finds a way to create exceptions to every model we propose.  Thus, it seems unwise to expect that functional diversification after gene duplication follows the same pathway every time.  Sometimes, subfunctionalization may occur by drift alone.  On other occasions, as we know, positive selection is involved.  Perhaps there are even cases where a new function has arisen by Ohno’s model of resuscitation of a dead gene. 

• Somewhere in the mix:  Hughes briefly elaborated on the possibility that new function is an emergent property from the mix and match of dynamic interplays between multi-talented genes and proteins:
  

  In fact, as recent data on gene expression and protein-protein interaction networks make clear, all genes are multifunctional.  Even in its infancy, systems biology makes clear that protein functions are complex processes existing in multiple dimensions.  It thus seems a reasonable extension of Jensen’s original insight to propose that new protein functions arise as the multidimensional space of functional interactions is parceled out in new ways, new links in biological networks are formed, and old links are broken.

In his concluding paragraph, Hughes made it clear that the proof is left as an exercise:

Testing this hypothesis will require work at the interface of molecular evolutionary genetics and systems biology.  We will need to be able to understand the diversification of gene duplicates in terms of the totality of each gene’s role in cellular processes.  It is a tall order given our present knowledge, but this kind of evolutionary systems biology not only will increase our understanding of how new protein functions evolve but also will shed essential light on why biological systems work the way they do.

¹Austin L. Hughes, “Gene duplication and the origin of novel proteins,” Proceedings of the National Academy of Sciences USA, published online before print June 13, 2005, 10.1073/pnas.0503922102.

This article sounded intriguing by its title, “Gene duplication and the origin of novel proteins,” and ostensibly set out to explain how new functions arose – but it did nothing of the sort.  All Hughes could identify by observation were degradation effects.  If genes and proteins underwent subfunctionalization, the function was already operative in the ancestor, as well as the information needed to produce function.  Did he prove that the daughter products contained more information?  No.  Did he prove that subfunctionalization actually occurred, rather than being created that way?  No.  Did he give away the store?  Yes.
    Hughes illustrated for the perceptive reader that Darwinian theory is useless and bankrupt.  It has produced little else than dangerous facile generalizations with exceptions for every proposed rule.  He has cast doubt on whether natural selection, the evolutionary mechanism that made Charlie the Philosopher-King of Science, acts as anything more than a conservative process to preserve existing information.  He tossed in for free a few falsifications of his colleagues’ speculative hypotheses.  He made up a story committing the personification fallacy about molecular Babe Ruths, without proving it has any relevance to real genes and proteins.  He demonstrated that evolutionary biology is an unending series of falsified tales, and he admitted that after “a century and a half of evolutionary biology,” almost nothing is known and everything remains to be discovered, which is “a tall order given our present knowledge” (better, lack of it).  So much for the origin of novel proteins.
    We provided extensive quotes from this paper to illustrate a recurring theme in the evolutionary scientific literature: Darwinists boast much but deliver nothing, only emptiness and confusion.  Does this vain litany of excuses and leaps in the dark deserve to be enshrined as the only valid approach to science, such that no student should be allowed to criticize it or hear any alternatives?