On the utility of evolution in experimental biology and medicine

A recurring theme amongst ID antievolutionists holds that evolution really doesn’t contribute useful directions or concepts in the realm of biology or medicine. Philip Skell regurgitates the theme in a recent commentary in Forbes magazine:

“Examining the major advances in biological knowledge, one fails to find any real connection between biological history and the experimental designs that have produced today’s cornucopia of knowledge of how the great variety of living organisms perform their functions. It is our knowledge of how these organisms actually operate, not speculations about how they may have arisen millions of years ago, that is essential to doctors, veterinarians, farmers and other practitioners of biological science.”

And later:

“The essence of the theory of evolution is the hypothesis that historical diversity is the consequence of natural selection acting on variations. Regardless of the verity it holds for explaining biohistory, it offers no help to the experimenter–who is concerned, for example, with the goal of finding or synthesizing a new antibiotic, or how it can disable a disease-producing organism, what dosages are required and which individuals will not tolerate it. Studying biohistory is, at best, an entertaining distraction from the goals of a working biologist.”

The blogosphere (and probably print media) are replete with summaries and specific cases that show Skell’s assertions to be a crock. This essay summarizes one such example. I have chosen this one because it refutes, specifically, the claim that an understanding of the evolutionary history of an organism “offers no help to the experimenter–who is concerned, for example, with the goal of finding or synthesizing a new antibiotic, or how it can disable a disease-producing organism”. It also ties Skell’s uninformed comments in with another subject that causes ID antievolutionists much consternation – the origins and evolution of organelles.

My response

There’s been a bit of a kerfluffle about a suggestion (challenge) made by a Discovery Institute associate to a professor of biology at the University of Vermont.  The first paragraph:

“Dear Professor Gotelli,

I saw your op-ed in the Burlington Free Press and appreciated your support of free speech at UVM. In light of that, I wonder if you would be open to finding a way to provide a campus forum for a debate about evolutionary science and intelligent design. The Discovery Institute, where I work, has a local sponsor in Burlington who is enthusiastic to find a way to make this happen. But we need a partner on campus. If not the biology department, then perhaps you can suggest an alternative.”

There have been a variety of “responses” to this challenge floating around the blogosphere.  Gotelli himself responded thusly:

Behe and the limits of evolution

Intelligent Design proponent Michael Behe has recently taken Ken Miller to task for the latters rough handling of another ID proponent’s handling of some concepts in evolution.  I don’t intend to add to the back and forth between the two (or three?) of them here.  Rather, I thought I would use one of Behe’s closing remarks as an excuse to repost a (slightly-modified) Panda’s Thumb essay that pertains to one of Behe’s newer calling cards – the so-called “Edge of Evolution”.

In the last paragraph of his response to Miller, Behe says:

“It’s pertinent to remember here the central point of The Edge of Evolution. We now have data in hand that show what Darwinian processes can accomplish, and it ain’t much.”

Actually, as the following essay clearly shows, Darwinian processes can do much more than Behe suggests.  Enjoy.

Axe (2004) and the evolution of enzyme function

[Preface - the subject of protein evolution pops up on a regular basis in ID circles.  Recently, William Dembski mentioned the study alluded to in the title of this essay as an improved argument/piece of evidence for intelligent design.  Specifically, Dembski said:

"(2) The challenge for determining whether a biological structure exhibits CSI is to find one that’s simple enough on which the probability calculation can be convincingly performed but complex enough so that it does indeed exhibit CSI. The example in NFL ch. 5 doesn’t fit the bill. The example from Doug Axe in ch. 7 of THE DESIGN OF LIFE (www.thedesignoflife.net) is much stronger."

"The example from Doug Axe in ch. 7 of THE DESIGN OF LIFE" would appear to be Axe's 2004 paper in the Journal of Molecular Biology, the subject of my first ever essay on The Panda's Thumb.  Since I have been a bit remiss in re-posting older essays here, I thought I would use this excuse to put this here.  It's "published" without change, so as to maintain some sort of continuity.  As always, enjoy.]

Douglas Axe recently (well, sort of) published an article in the Journal of Molecular Biology entitled “Estimating the Prevalence of Protein Sequences Adopting Functional Enzyme Folds” (Axe, J Mol Biol 341, 1295-1315, 2004). In his discussion of the experimental observations, Dr. Axe mentions some numbers that are likely to generate much discussion amongst Intelligent Design advocates and critics. For example, Stephen Meyer (2004) cites Axe at a key point in the argument in his recent article advocating Intelligent Design, “The Origin of Biological Information and the Higher Taxonomic Categories,” much discussed in previous Panda’s Thumb threads (here).

“Axe (2004) has performed site directed mutagenesis experiments on a 150-residue protein-folding domain within a B-lactamase enzyme. His experimental method improves upon earlier mutagenesis techniques and corrects for several sources of possible estimation error inherent in them. On the basis of these experiments, Axe has estimated the ratio of (a) proteins of typical size (150 residues) that perform a specified function via any folded structure to (b) the whole set of possible amino acids sequences of that size. Based on his experiments, Axe has estimated his ratio to be 1 to 10^77. Thus, the probability of finding a functional protein among the possible amino acid sequences corresponding to a 150-residue protein is similarly 1 in 10^77.”

More recently, Dembski cited Axe in his Expert Witness Report for the Dover trial (see this).

“Recent research by Douglas Axe (see Appendix 3) provides such evidence in the form of a rigorous experimental assessment of the rarity of function-bearing protein sequences. By addressing this problem at the level of single protein molecules, this work provides an empirical basis for deeming functional proteins and systems of functional proteins to be unequivocally beyond Darwinian explanation.”

Given that this subject is often raised by ID proponents (such as this), and that the Biologic Institute (where Axe works) has made some news accounts, it seems appropriate to review Axe’s work. The purpose of this PT blog entry is to try and lay out the study cited above (Axe DD, J Mol Biol 341, 1295-1315, 2004) in a form that is accessible to most interested parties, and to discuss a larger context into which this work might be placed. Needless to say, the grand pronouncements being made by the ID camp are not warranted.

Is macroevolution impossible to study (Part 2)?

The plant kingdom is many things – the basis of agriculture and civilization, a natural laboratory with a stupefying capability in organic synthesis, a source of untold numbers of pharmaceuticals, antimicrobials, herbals, and other chemical playthings, a fascinating range of biological form and function, and an eminently accessible subject for studies of evolution. Along the lines of the last two bullets, one of the more interesting aspects of plants is the range of growth habits that may be adopted. Among these are two sets of contrasting characteristics – annual or perennial, and herbaceous or woody. Differences in these characteristics are among the bases for classification of plant species. For this reason, but also because accompanying morphological differences can be quite considerable, evolutionary changes that involve transitioning between these states are macroevolutionary. Thus, it stands to reason that studying the means by these characteristics evolve amounts to experimental analysis of macroevolution, and understanding the underlying mechanisms constitutes an explanation of macroevolutionary processes.

It is in this light that a recent report deserves some attention. This report, by Melzer et al., describes studies of the functioning of two regulators of flowering in the herbaceous annual Arabidopsis thaliana. These proteins, called SOC1 and FUL, had been known for some time to be involved in the regulation of flowering. Melzer et al. constructed double mutants deficient in the expression of these two proteins, with the intent of understanding the physiological significance of interactions between these two proteins, associations discovered using the so-called yeast two-hybrid assay. Amazingly, soc1 ful double mutants were dramatically different – they had a more woody growth habit, and they behaved like perennials when it comes to reproduction. The abstract from the paper follows this paragraph. The bottom line that is in keeping with the title of the essay – not only can this particular macroevolutionary process be studied experimentally, it can be understood and the corresponding macroevolutionary process recapitulated in a controlled setting.

The abstract:

Plants have evolved annual and perennial life forms as alternative strategies to adapt reproduction and survival to environmental constraints. In isolated situations, such as islands, woody perennials have evolved repeatedly from annual ancestors1. Although the molecular basis of the rapid evolution of insular woodiness is unknown, the molecular difference between perennials and annuals might be rather small, and a change between these life strategies might not require major genetic innovations2, 3. Developmental regulators can strongly affect evolutionary variation4 and genes involved in meristem transitions are good candidates for a switch in growth habit. We found that the MADS box proteins SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1) and FRUITFULL (FUL) not only control flowering time, but also affect determinacy of all meristems. In addition, downregulation of both proteins established phenotypes common to the lifestyle of perennial plants, suggesting their involvement in the prevention of secondary growth and longevity in annual life forms.

The citation:

Melzer S, Lens F, Gennen J, Vanneste S, Rohde A, Beeckman T. 2008. Flowering-time genes modulate meristem determinacy and growth form in Arabidopsis thaliana. Nature Genetics, published online: 9 November 2008 | doi:10.1038/ng.253

Is macroevolution impossible to study?

Once again, the Discovery Institute is playing word games with educational systems, trying to give legal protection to religion-based incompetence.  I refer, of course, to the ongoing debate about standards in Texas, and the insidious influence that the DI is wielding.

As Wesley Elsberry notes in his summary of the alleged weaknesses of evolutionary theory, an oft-repeated mantra rears its head yet again.  This ID tenet holds that macroevolution is either not possible, or cannot be observed, or cannot be studied (or any combination of the these).  Apparently, Board of Education member Ken Mercer is of the opinion that macroevolution has not been observed.

Protocells, the origins of life, and the RNA World

This essay is a bit less formal than many I’ve posted here, more of an indulgence than the cut-and-dried stuff I’ve been posting about polyadenylation. It is essentially a repost of an essay I posted on the old ARN boards many years ago. I’m moved to this by a recent a recent article in PNAS. The overall context is the origin of life, and some of the different arguments and perspectives that are brought to the table in ev/cre debates.

As a segue, the abstract of the PNAS article:

“Life is that which replicates and evolves. The origin of life is also the origin of evolution. A fundamental question is when do chemical kinetics become evolutionary dynamics? Here, we formulate a general mathematical theory for the origin of evolution. All known life on earth is based on biological polymers, which act as information carriers and catalysts. Therefore, any theory for the origin of life must address the emergence of such a system. We describe prelife as an alphabet of active monomers that form random polymers. Prelife is a generative system that can produce information. Prevolutionary dynamics have selection and mutation, but no replication. Life marches in with the ability of replication: Polymers act as templates for their own reproduction. Prelife is a scaffold that builds life. Yet, there is competition between life and prelife. There is a phase transition: If the effective replication rate exceeds a critical value, then life outcompetes prelife. Replication is not a prerequisite for selection, but instead, there can be selection for replication. Mutation leads to an error threshold between life and prelife.”

Polyadenylation, histone mRNAs, and the evolution of irreducible complexity

As if on cue, a new study reinforces some ideas I discussed in another essay.  This report from Joan Steitz’ lab shows that both CPSF73 and CPSF100 contribute important residues for the endonuclease responsible for maturation of histone mRNAs*.  The abstract:

“In eukaryotes, the process of messenger RNA 3′-end formation involves endonucleolytic cleavage of the transcript followed by synthesis of the poly(A) tail. The complex machinery involved in this maturation process contains two proteins of the metallo-beta-lactamase (MBL) superfamily, the 73 and 100 kDa subunits of the cleavage and polyadenylation specificity factor (CPSF). By using an in vitro system to assess point mutations in these two mammalian proteins, we found that conserved residues from the MBL motifs of both polypeptides are required for assembly of the endonuclease activity that cleaves histone pre-mRNAs. This indicates that CPSF73 and CPSF100 act together in the process of maturation of eukaryotic pre-messenger RNAs, similar to other members of the MBL family, RNases Z and J, which function as homodimers.”

The functional and evolutionary implications are fascinating.  Of particular note are the possible roles that gene duplication may have played in the origins of the eukaryotic polyadenylation complex (recall that CPSF73 and CPSF100 are themselves related at the sequence level, and are both metallo-beta-lactamase family members), and the functional similarities with bacterial metallo-beta-lactamase nucleases.  It is also interesting to see how a shared core (CPSF) has assumed different functions, through interactions with different “accessory factors”.  (The notion that U7 and CstF are “accessory factors” is a bit unconventional, to be sure.)  And of course, in keeping with one theme of this blog, the implications that this emerging story has for the origins and evolution of irreducibly complex systems are considerable.

The citation:

Nikolay G Kolev, Therese A Yario, Eleni Benson, Joan A Steitz (2008). Conserved motifs in both CPSF73 and CPSF100 are required to assemble the active endonuclease for histone mRNA 3′-end maturation EMBO reports, 9 (10), 1013-1018 DOI: 10.1038/embor.2008.146

*  astute readers may recall that cell-cycle-regulated histone mRNAs are not polyadenylated.  Instead, they have distinctive structures at their 3’ ends, which are formed by a complex that includes the snRNP U7.  It turns out that many of the additional proteins that act in concert with U7 are identical to subunits of the polyadenylation complex.  CPSF73 and CPSF100 are two of these; the scaffolding protein symplekin is another.

Giardia lamblia, polyadenylation, and irreducible complexity

Several of the introductory essays in this blog have dealt with aspects of polyadenylation and the complex that mediates this process.  As shown in this figure and as discussed (in part) here and here, the complex is sizeable and possesses a number of activities, including some that seem superfluous.  However, genetic studies in yeast indicate that virtually every subunit of the core complex is essential – for viability and for pre-mRNA processing and polyadenylation in vitro and in vivo.  Biochemical and/or immunological depletion studies reveal a similar scenario in mammals, and a less-expansive set of studies suggests that a similar rule of thumb will apply in plants.  The bottom line of all of this is that almost all of the subunits of the polyadenylation complex seem to be essential.  In the vernacular of a proponent of intelligent design, the polyadenylation complex would seem to be irreducibly complex.

It is in this context that the recently-completed genome of the parasitic organism Giardia lamblia enters the fray.  Last year, the complete sequence of G. lamblia, some 12 million base pairs, was determined and analyzed.  The authors of the study published in Science noted a number of interesting things – a preponderance of genes encoding protein kinases, evidence for substantial horizontal gene flow from bacteria and archaebacteria, and a streamlined core gene expression machinery (transcription and RNA processing).  This streamlining is especially notable in the case of the polyadenylation machinery.  Remarkably, of all the subunits pictured in this figure, genes for only three* can be found in G. lamblia (see the figure that follows this paragraph).

One person’s junk is another’s treasure

In previous essays (here and here), we learned that genes encoding new proteins can and do, often, arise de novo in the course of evolution, contradicting one of the central tenets of ID proponents.  The means by which these genes arise are many.  One of these, suggested by Cai at al. (the subject of one of the earlier essays), involved the adaptation of a gene encoding an evolutionarily-conserved non-coding RNA via the appearance, by mutation, of appropriate translation initiation and termination (“start” and “stop”) codons.  This mechanism represents an intersection of sorts between the subject of protein evolution and another matter of discussion on these blogs, namely the existence, evolution, and “function” of junk DNA.  In this essay, I review a 2007 study by Debrah Thompson and Roy Parker (“Cytoplasmic decay of intergenic transcripts in Saccharomyces cerevisiae”, Mol. Cell. Biol. 27, 92-101) that adds a great deal of clarity to this mode of gene and protein evolution.