To Build New Animals, No New Genetic Information Needed? More in Reply in Charles Marshall

Stephen C. Meyer October 7, 2013

In my previous article responding to Charles Marshall, I argued that his review of Darwin's Doubt in the journal Science ("When Prior Belief Trumps Scholarship") illustrates what has become all too common in the defense of contemporary evolutionary theory: the tendency to affirm as true what evolutionary theory requires, even if that contradicts what we know from experiment and observation about how biological systems actually work. Now I will show that in order to rebut the central argument of Darwin's Doubt, Marshall must also deny (or at least push from view) what we know about what new forms of animal life require as a condition of their existence.

In Darwin's Doubt, I argue that intelligent design provides the best explanation for the origin of the genetic (and epigenetic) information necessary to produce the novel forms of animal life that arose in the Cambrian period. To his credit, and unlike other critics of the book, Marshall addresses this, the main argument of the book, and attempts to refute it. To do so, however, he does not show that any of the main materialistic evolutionary mechanisms can produce the information necessary to build the Cambrian animals. Instead, Marshall disputes my claim that significant amounts of new genetic information (and many new protein folds) would have been necessary to build these animals. Specifically, Marshall claims that "rewiring" of dGNRs would have sufficed to produce new animals from a set of preexisting genes. As he argues:

[Meyer's] case against the current scientific explanations of the relatively rapid appearance of the animal phyla rests on the claim that the origin of new animal body plans requires vast amounts of novel genetic information coupled with the unsubstantiated assertion that this new genetic information must include many new protein folds. In fact, our present understanding of morphogenesis indicates that new phyla were not made by new genes but largely emerged through the rewiring of the gene regulatory networks (GRNs) of already existing genes.¹

Yet Marshall's understanding of how animal life originated is problematic for several reasons.

Rewiring Requires Information

First, "rewiring" genetic circuitry would require reconfiguring the temporal and spatial expression of genetic information. Such reconfiguring would entail fixing certain material states and excluding others. Thus, it would constitute an infusion of new information (in the most general theoretical sense) into the biosphere.² To see why, consider changing a wiring diagram representing a developmental gene regulatory network. Just altering the diagram representing the network to produce a new diagram representing a new network would require changing the arrangement of "nodes" (representing genes) and "edges" (representing interactions between genes and gene products). Changing the arrangement of these elements in order to produce a new network would constitute adding information into the diagram depicting the system. In the same way, changing the arrangements of genetic elements themselves in an actual network would also require informative changes to the arrangement of the network. Thus, Marshall's "rewiring" proposal does not eliminate the need for new information to build the Cambrian animals. Rather, it tacitly invokes additional information of a different, though perhaps partially non-genetic, kind.

In any case, altering the temporal and spatial expression of pre-existing genetic elements assuredly would require the addition of new taxon-specific genes or gene products, and thus, new genetic information. Indeed, experiments on dGRNs in modern representatives of the animal phyla show that different organisms use taxon-specific DNA-binding proteins to regulate the expression of genetic data files. For instance, contrary to theoretical expectations,³ the morphogen Bicoid, essential for normal anterior-posterior body plan specification in Drosophila, is found only in the cyclorrhaphan flies.⁴ Similarly, the body plan of the freshwater polyp Hydra is specified by taxonomically restricted proteins.⁵ Nor are these isolated cases. The remarkable disparity of animal morphologies at the macroscopic (i.e., anatomical or body plan) level tends to correspond to differences at other levels (i.e., the microscopic or molecular). Moreover, studies of "evo-devo" model systems have repeatedly revealed that the cell and tissue specification programs that generate distinctive animal morphologies depend upon taxon-specific regulatory factors (proteins and RNAs). As Oliveri and Davidson note:

...the specification apparatus very frequently also includes transcriptional repressors, which, within the specified spatial domain, target key regulatory genes whose expression is required for alternative regulatory states that could have been available to these cells. This is a so-called "exclusion effect," and numerous examples can be found across species...In each developmental case, the identity of the specific transcription factor that executes the repression is distinct, as are the specifically excluded target transcription factors. The design is the same, the biochemical actors diverse.⁶

Of course, building these species-specific transcription factors necessary to animal development requires genetic information. And the origin of these proteins in the first place would have required the origin of new genetic information.

Ubiquitous ORFan Genes

Second, recent genomic studies of many animals representing phyla that first arose in the Cambrian show that these animals depend upon many unique genes not present in any other taxa. Moreover, these genes perform many functions besides just specifying body plan development. These sequences, known as taxonomically restricted or "ORFan" genes, are ubiquitous in all animal life and represent 10% or more of the genomes of each species that scientists have investigated.⁷

The presence of ORFan genes in all sequenced present-day animal genomes -- and, indeed, in all life⁸ -- suggests that the genomes of Cambrian animals would have likely contained many ORFan genes as well. That, in turn, suggests that a considerable amount of new genetic information not present in simpler Precambrian organisms would have originated before or during the Cambrian radiation in order to build the unique features of the first Cambrian animals. Moreover, even if some universal Precambrian genome originally contained all the genes that later became taxonomically restricted, whatever process distributed these genes to some lineages, but not others, necessarily involved the addition of new information into the biosphere.⁹

A Telling Admission

Interestingly, in his review and especially when writing elsewhere, Marshall acknowledges the need for new genes and genetic information in order to produce the Cambrian animals. For example, in a 2006 paper entitled "Explaining the Cambrian 'Explosion' of Animals," he noted that: "Animals cannot evolve if the genes for making them are not yet in place. So clearly, developmental/genetic innovation must have played a central role in the radiation."¹⁰ Later in the same paper he argues that: "It is also clear that the genetic machinery for making animals must have been in place, at least in a rudimentary way, before they could have evolved."¹¹ Marshall insists that Hox genes, in particular, must have played a necessary causal role in producing the explosion, a point that he also makes in another paper where he explains that developmental considerations "point to the origin of the bilaterian developmental system, including the origin of Hox genes, etc., as the primary cause of the 'explosion.'"¹² While in these papers Marshall also emphasizes the importance of rewiring gene regulatory networks to generate new body plans, he clearly acknowledges that new genes would be necessary to produce new animals.

New Animals Require Many New Cell Types and Specialized Proteins

Of course, building the Metazoa (multi-cellular animals) would not have just required new Hox genes, ORFan genes, or genes for building new regulatory (DNA-binding) proteins. Instead, the evolutionary process would need to produce a whole range of different proteins necessary to building and servicing the specific forms of animal life that arose in the Cambrian period. In Darwin's Doubt I note, for example, that the first arthropods would have likely required genes for building the complex protein lysyl oxidase.¹³ Why? Because what we know from studies of modern arthropods shows that this protein is necessary to support the stout body structure of arthropod exoskeletons.¹⁴ Similarly, building Metazoa requires specialized proteins (and metabolic pathways) to produce the kind of extra-cellular matrices that allow developing animals to knit cells into tissues, tissues into organs, and organs and tissues into fully developed animals. Furthermore, different forms of complex animal life exhibit unique cell types and typically each cell type depends upon other specialized or dedicated proteins. As I wrote in Darwin's Doubt:

[new] complex animals [such as arose in the Cambrian period] require more cell types to perform their more diverse functions. Arthropods and mollusks, for example, have dozens of specific tissues and organs, each of which requires "functionally dedicated," or specialized, cell types. These new cell types, in turn, require many new and specialized proteins. An epithelial cell lining a gut or intestine, for example, secretes a specific digestive enzyme. This enzyme requires structural proteins to modify its shape and regulatory enzymes to control the secretion of the digestive enzyme itself. Thus, building novel cell types typically requires building novel proteins, which requires assembly instructions for building proteins -- that is, genetic information.¹⁵

Thus, our present observations of animals representing the phyla that first arose in the Cambrian show that these animals would have needed many specialized proteins: proteins for building extracellular matrices or exoskeletons, for facilitating adhesion, for regulating development, for building specialized tissues or structural parts of specialized organs, for servicing gut cells, for producing eggs and sperm as well as many other distinctive functions and structures of individual metazoans. Obviously, these proteins would have had to arise sometime in the history of life. Since most of the Metazoa first arose in the Cambrian explosion, it is reasonable to infer that the proteins necessary to sustain those forms of animal life also arose around that time or just before.

Begging the Central Question

Although Marshall characterizes my claim that new Cambrian animals would have required new genetic information and new protein folds as "unsubstantiated," he doesn't actually dispute the need for genetic information in order to build the proteins required by each new form of metazoan life. Instead, he only seems to dispute that all that information arose during the Cambrian explosion itself. Indeed, in both his technical publications and his review of Darwin's Doubt, Marshall simply assumes that most of the genetic information necessary to build the Cambrian animals already existed before the Cambrian explosion. In fact, he seems to presuppose the existence of what Susumu Ohno called a "pananimalian genome,"¹⁶ a nearly complete set of the genes necessary to build Cambrian animals within some phenotypically simpler, ur-metazoan ancestor. Thus, he states the new animal phyla "emerged through the rewiring of the gene regulatory networks (GRNs) of already existing genes."¹⁷ The article "The Causes of the Cambrian Explosion," which accompanies Marshall's review of my book in Science, also presupposes such a universal gene toolkit and suggests that it might have arisen 100 million years or more before the explosion of animal life in the Cambrian period.¹⁸

Nevertheless, this question-begging assumption does not solve the central problem posed by Darwin's Doubt -- that of the origin of the genetic (and epigenetic) information necessary to produce the Cambrian animals. It merely pushes the problem back several tens or hundreds of millions of years, assuming that such a universal genetic toolkit ever existed. (Marshall also makes no attempt to rebut my argument about the inability of the mutation/selection mechanism to generate new epigenetic information, a problem that has led other prominent evolutionary biologists to express skepticism about the adequacy of the neo-Darwinian mechanism.¹⁹) In any case, Marshall does not explain how the neo-Darwinian mechanism could have overcome the combinatorial search problem described in Darwin's Doubt to produce even the new genetic information necessary to build new proteins and Cambrian animals.

Readers of the book will recall my discussion, in Chapters 9 and 10, of recent mutagenesis experiments. These experiments have established the extreme rarity of functional genes and proteins among the many (combinatorially) possible ways of arranging nucleotide bases or amino acids within their corresponding "sequence spaces." Readers will also recall that the rarity of functional genes and proteins within sequence space makes it overwhelmingly more likely than not that a series of random mutation searches will fail to generate even a single new gene or protein fold within available evolutionary time. This extreme rarity also helps to explain why mathematical biologists, using standard population genetics models, are calculating exceedingly long waiting times (well in excess of available evolutionary time) for the production of new genes and proteins when producing such genes or proteins requires even a few coordinated mutations.²⁰

For these reasons, defining the Cambrian explosion as a 25 million year event, as Marshall does, instead of a 10 million year event, as many other Cambrian experts do (and as I do in Darwin's Doubt), makes no appreciable difference in solving the problem of the origin of genetic information -- such is the extreme rarity of functional bio-macromolecules within their relevant sequence spaces. Nor, for that matter, does positing the origin of a complete set of genes (that is, many more than just one) for building all the Cambrian animals 100 million years before the Cambrian explosion. That merely pushes the problem back and raises other problems such as (a) explaining exactly what selective advantage all these genes for building new animals would have had before they were actually used to build the diverse animals that arose in the Cambrian and (b) how the maintenance of this overly complex genome could have avoided exacting a huge energetic and fitness cost on its host organism, and thus the effects of purifying selection over 100 million years of evolutionary time.

In any case, the experimentally based calculations in Darwin's Doubt show that neither ten million, nor several hundred million years would afford enough opportunities to produce the genetic information necessary to build even a single novel gene or protein, let alone all the new genes and proteins needed to produce new animal forms. Indeed, neither stretch of time is sufficient to allow the mutation/selection process to search more than a tiny fraction of the relevant sequence spaces. Marshall's review does not even allude to a solution to this longstanding mathematical,²¹ and now experimentally based,²² challenge to the efficacy of the neo-Darwinian mechanism. Instead, his proposal merely presupposes the prior existence of the genetic information necessary to produce the Cambrian animals.

In my next article, I'll address Marshall's claim that the positive argument for intelligent design that I make in the book actually constitutes a wholly negative or critical "God-of-the gaps" argument.

NOTES:

(1) Charles R. Marshall, "When Prior Belief Trumps Scholarship," Science 341 (September 20, 2013): 1344.

(2) See: Claude Shannon, "A Mathematical Theory of Communication," Bell System Technical Journal 27 (1948): 370-423, 623-29.

(3) Nicolas Rasmussen, "A New Model of Developmental Constraints as Applied to the Drosophila System," Journal of Theoretical Biology 127 (1987): 271-99.

(4) David Rudel and Ralf Sommer, "The evolution of developmental mechanisms," Developmental Biology 264 (2003): 15-37; p. 25: "Phylogenetic evidence suggests that bcd may be a new innovation in the anterior positional information gene network during the evolution of Dipterans. Despite repeated attempts, it has not been possible to clone bcd homologues outside of the Cyclorraphan flies (Stauber et al., 1999). Additionally, bcd is not present in the Antennapedia complex of the flour beetle Tribolium castaneum (Brown et al., 2002). This has caused speculation that bcd may have evolved late in the evolution of the Dipterans."

(5) Konstantin Khalturin, Friederike Anton-Erxleben, Sylvia Sassmann, Jörg Wittlieb, Georg Hemmrich, Thomas C. G. Bosch, "A Novel Gene Family Controls Species-Specific Morphological Traits in Hydra," PLoS Biology 6 (2008): e278.

(6) Paolo Oliveri and Eric H. Davidson, "Built to Run, Not to Fail," Science 315 (2007): 1510-11 (emphasis added).

(7) Amanda K Gibson, Zach Smith, Clay Fuqua, Keith Clay and John K. Colbourne, "Why so many unknown genes? Partitioning orphans from a representative transcriptome of the lone star tick Amblyomma americanum," BMC Genomics 14 (2013): 135.

(8) Konstantin Khalturin, Georg Hemmrich, Sebastian Fraune, René Augustin and Thomas C.G. Bosch, "More than just orphans: are taxonomically-restricted genes important in evolution?" Trends in Genetics 25 (2009): 404-13.

(9) Marshall seems to have an idiosyncratic view of animal evolution, depicting the evolution of animals as a reductive process in which pre-existing genetic information from a universal Precambrian gene set is selectively lost to some lineages but not to others. This contrasts markedly with a more standard neo-Darwinian view in which form and information gradually accumulate over time.

(10) Charles R. Marshall, "Explaining the Cambrian 'Explosion' of Animals," Annual Reviews of Earth and Planetary Sciences 34 (2006): 355-84.

(11) Ibid.

(12) Charles R. Marshall, "Nomothetism and Understanding the Cambrian 'Explosion,'" Palaois 18: 195-96 (June, 2003).

(13) See Darwin's Doubt, p. 191.

(14) Susumu Ohno, "The notion of the Cambrian pananimalia genome," Proceedings of the National Academy of Sciences, U.S.A. 93 (1996): 8475-78.

(15) Darwin's Doubt, p. 162.

(16) Susumu Ohno, "The notion of the Cambrian pananimalia genome," Proceedings of the National Academy of Sciences, U.S.A. 93 (1996): 8475-78.

(17) Charles R. Marshall, "When Prior Belief Trumps Scholarship," Science 341 (September 20, 2013): 1344 (emphasis added).

(18) M. Paul Smith and David A. T. Harper, "Causes of the Cambrian Explosion," Science 341 (September 20, 2013): 1355-56. (Smith and Harper propose "an apparent >100-million-year gap between the evolutionary innovation and its consequences.")

(19) Gerd B. Müller and Stuart A. Newman, "Origination of Organismal Form: The Forgotten Cause in Evolutionary Theory."In: Origination of Organismal Form: Beyond the Gene in Developmental and Evolutionary Biology, Edited by Gerd B. Müller and Stuart A. Newman. Cambridge, MA: MIT Press, 2003, 7-8.

(20) See Darwin's Doubt, Chapters 9-12.

(21) Murray Eden, "Inadequacies of Neo-Darwinian Evolution as a Scientific Theory." In: Mathematical Challenges to the Neo-Darwinian Interpretation of Evolution, edited by P. S. Moorhead and M. M. Kaplan, 9-11. Wistar Institute Symposium Monograph. New York: Liss, 1967. Marcel Schützenberger, "Algorithms and the Neo-Darwinian Theory of Evolution." Also in: Mathematical Challenges to Neo-Darwinian Theory of Evolution. 73-80.

(22) John Reidhaar-Olson, and Robert Sauer. "Functionally Acceptable Solutions in Two Alpha-Helical Regions of Lambda Repressor." Proteins: Structure, Function, and Genetics 7 (1990): 306-16. Douglas D. Axe, "Estimating the Prevalence of Protein Sequences Adopting Functional Enzyme Folds," Journal of Molecular Biology 341 (2004): 1295-1315.

- See more at: http://www.evolutionnews.org/2013/10/to_build_new_an077541.html#sthash.tnah3lqz.dpuf

Paper: "Irreducible Organization" of DNA Necessary for Genetic Regulation

Casey Luskin October 11, 2013 

A new paper in the journal Cellular and Molecular Life Sciences, "Integration of syntactic and semantic properties of the DNA code reveals chromosomes as thermodynamic machines converting energy into information," argues that cellular mechanisms involved in processing genetic information make up an irreducibly complex system. The system requires genetic information, genetic machinery keyed to read that genetic information, as well as specific chromosomal organization. All of these components are necessary for what the paper calls "the organisational complexity of the genetic regulation system."

To be precise, the paper uses the term "irreducible organization" but it amounts to the same thing as biochemist Michael Behe's "irreducible complexity," and points implicitly to the same challenge to Darwinian accounts of origins.

The paper aims to critique the reductionist "Jacob-Monod paradigm," which fails to appreciate the complexity of genetic information, as well as the interaction between transcription factors and their target genes. Of course we're all familiar with genetic information in DNA being required to produce proteins. But the paper argues that in addition to the "digital information" in the primary DNA sequence, there is also "analog information" in the three-dimensional structure of chromosomes:

Recent studies have made it increasingly evident that the primary sequence of DNA in addition to the linear genetic code also provides three-dimensional information by means of spatially ordered supercoil structures relevant to all DNA transactions, including transcriptional control. In this review, we adopt the previously introduced terms "analog" and "digital" with regard to the two logically distinct types of information provided by the DNA. ... [A]ny DNA gene is a carrier of digital information by virtue of its unique base sequence. Moreover, a gene conceived as an isolated piece of linear code (no matter whether this isolation occurs at the level of transcription or posttranscriptional processing), is a discontinuous entity that can be expressed or not, thus principally consistent with an "on-or-off" logic and, therefore, belonging to digital information type. Conversely, the physicochemical properties of DNA, as exemplified by supercoiling and mechanical stiffness, are determined not by individual base pairs but by the additive interactions of successive base steps. Supercoiling is by definition a continuous parameter ranging between positive and negative values (you can have more or less of it), and so belongs to analog information type.

On top of the various forms of information in DNA, chromosomal structure is vital for gene regulation, as it helps control the interaction between transcription factors (TFs) that initiate transcription of their target genes (TGs):

several studies have proposed that the organisation of chromosomal structure on the evolutionary time scale is largely determined by the need of spatial optimisation of TF-TG interactions.

The paper then argues that the system of genetic regulation in cells is characterized by "irreducible organization":

Genetic regulation is crucial not only for sustaining the self-reproduction of a cell but also for substituting its worn-out constituents. This implies that a genetic regulation system, as a system consisting of physical elements, must be able not only to perform its primary function but also to perceive any internal changes of state so that it retains the potential, for example, to replenish its own components. In other words, it has to be self-referential. This peculiarity of organisation becomes conspicuous when compared to information coding in natural language, the syntactic and semantic properties of which provide logically different types of information. Syntax determines the structure of the rules of language and, thus, the way in which the words are assembled in sentences, whereas semantics determine the meaning of the words and so the available vocabulary. However, the structural rules of language cannot determine the meanings of the words, and nor is the vocabulary determinative for the structural rules of the language (we do not concern ourselves with any generative mechanisms relevant to the formal language theory here). Therefore, viewed as a coding system composed of two non-convertible types of information, natural language is not self-referential. By the same token, the Jacob-Monod paradigm separating the gene regulatory context from the genetic information is at variance with self-referential organisation. Notably, we do not use this term in the sense of elaborated mathematical concepts of distinction, circulation, feedback, re-entry, recursion, etc. Self-referential organisation, as we put it here, implies inter-conversion of information between logically distinct coding systems specifying each other reciprocally. Thus, the holistic approach assumes selfreferentiality (completeness of the contained information and full consistency of the different codes) as an irreducible organisational complexity of the genetic regulation system of any cell. Put another way, this implies that the structural dynamics of the chromosome must be fully convertible into its genetic expression and vice versa. Since the DNA is an essential carrier of genetic information, the fundamental question is how this self-referential organisation is encoded in the sequence of the DNA polymer.

The article even specifies that there are "Three basic components underlying the irreducible organisational complexity of any living cell" where "the organisation is essentially circular with all three basic components standing in relationship to reciprocal determination." Those three components are specified as transcriptional machinery, DNA topology, and metabolic energy. The authors are perplexed by how the "irreducible" and "circular" organization of this system arose since they admit, "we face a 'chicken or egg' dilemma -- on the one hand the TF-TG interactions are determinative for the chromosomal structure, and on the other hand this very same structure determines the regulatory interactions."

As noted, the paper recognizes that there are other types of information in DNA beyond merely the sequence of bases. What's incredible is that even though these two types of information are specified through different physical means, they nonetheless interact to regulate gene expression. The article explains that the supercoiling structure of DNA is vital to regulating gene expression, and at the same time it's not specified by the base-pair sequence. However, the base-pair sequence does interact with the supercoiling, and is more prone to "localized untwisting" to allow transcription:

In general, the regions of chromosomes that are sites for topological manipulation (such as, e.g., transcription and replication initiation sites) correlate strongly with low base stacking energies and high flexibility. Indeed, the sequences at the start sites of transcription and replication are prone to localised untwisting, whereas the termination sites -- and especially the regions between two converging translocases (be it a replisome or RNA polymerase) -- appear to easily adopt a writhed configuration acting as supercoil repositories. The emerging view is that manipulation of superhelical density and regulation of partitioning between twist and writhe is a fundamental property of both.

There are other levels of organization that have to do with the location and shape of the chromosome in time and space:

spatiotemporal integration of the analog (syntactic) and digital (semantic) properties of the chromosomal DNA code appears as a basic device coordinating the bacterial growth program. This coordination is facilitated by organising genes in a highly conserved order and orientation...

The article concludes: "chromosomes act as machines in which coordinated topological transitions operating at local (e.g. transcription initiation sites), regional (constrained superhelical domains) and global (entire chromosomes) levels specify the genetic activity."

All of this is pretty technical, but a summary sent to me by a pro-ID biologist helps explain how all of these difference levels of information are coordinated with one-another to facilitate basic cellular functions:

The authors describe the supercoiling (superhelicity) of the DNA, which affects levels of transcription in a rheostatic (analog) manner, is arranged in a gradient from the origin of replication to the terminus. Anabolic functions, which are expressed early in the cell cycle, show a preference to be on the leading strand (with regard to replication) and are organized close to the origin of replication, whereas catabolic functions are expressed late in the cell cycle, organized toward the terminal region of replication. Furthermore, the anabolic genes require high negative superhelicity for transcription, which is increased during rapid growth and therefore rapid replication of the DNA. So, during rapid growth, when anabolic functions become a limiting factor, a bottleneck if you will, the DNA replication generates more strain on the chromosome, i.e. more negative superhelicity, which is exactly the parameters for increasing anabolic functions. Brilliant.

How did these various independent levels of information become "coordinated"? Brilliance seems the best explanation for something brilliant.

http://www.evolutionnews.org/2013/10/paper_irreducib077761.html#sthash.ELI2pW4r.dpuf

Attempting to Win the Debate over Intelligent Design through Stereotyping

John G. West October 10, 2013 

stereotype... an often unfair and untrue belief that many people have about all people or things with a particular characteristic... especially: a standardized mental picture that is held in common by members of a group and that represents an oversimplified opinion, prejudiced attitude, or uncritical judgment.

Throughout history, people have used stereotypes to silence, subjugate, and dehumanize those they oppose. In American history, blacks, Jews, women, Catholics, and others have all been victims of this kind of mistreatment. Because stereotyping is so pernicious, the Society of Professional Journalists' Code of Ethics wisely instructs journalists to

Avoid stereotyping by race, gender, age, religion, ethnicity, geography, sexual orientation, disability, physical appearance or social status.

Unfortunately, when it comes to the issue of intelligent design (ID), many journalists throw their professional training out the door. Reporters who would never dream of caricaturing a woman or a gay person uncritically repeat as fact the tendentious claim that intelligent design proponents are "creationists." Reporters usually do this without even defining what creationism is, although the term is presumably meant to conjure up lurid images of (take your pick) Inherit the Wind, Bible-thumpers, witch trials, religious fundamentalism, and humans cavorting with dinosaurs a few thousand years ago.

Now I understand perfectly why opponents of intelligent design seek to caricature it with the term "creationism." They are trying to win the public debate without doing the hard work of actually rebutting the arguments offered by intelligent design proponents. Even some critics of intelligent design openly acknowledge that this is what is going on. Anti-ID historian of science Ron Numbers admitted several years ago to the Associated Press that "the creationist label is inaccurate when it comes to the ID movement," but added that critics of ID use the label because they think such claims are "the easiest way to discredit intelligent design." (To his credit, Numbers was not defending this tactic; he was simply acknowledging it.)

Reporters, of course, are supposed to be fair and impartial in their reporting, not partisans of one side of a debate. It's one thing for the critics of intelligent design to use straw-man arguments and stereotypes to smear ID proponents. It's another thing for news reporters to offer such stereotypes as a neutral description of intelligent design. Unfortunately, the cavalier and unthinking application of the term "creationist" to intelligent design proponents -- and anyone else critical of traditional Darwinian theory -- is rampant in the news media.

Consider the recent New York Times story that repeatedly invoked the terms "creationist" and "creationism" without bothering to define them, even insinuating that a scientist who accepts standard geological dating for the age of the Earth is a "creationist."

Or consider the recent article in the Muncie Star-Press in which reporter Seth Slabaugh wrongly claims that Discovery Institute is a "pro-creationism ... think tank." Come again?

As I pointed out to Slabaugh in subsequent correspondence, and in a letter to the editor published by his newspaper, Discovery Institute does not advocate creationism, nor does it favor its teaching in public schools. I highlighted for Slabaugh the following clear statements from our website:

Does Discovery Institute favor including the Bible or creationism in science classes or textbooks?

No. Discovery Institute is not a creationist organization, and it does not favor including either creationism or the Bible in biology textbooks or science classes. 

Is intelligent design theory the same as creationism?

No. Intelligent design theory is simply an effort to empirically detect whether the "apparent design" in nature acknowledged by virtually all biologists is genuine design (the product of an intelligent cause) or is simply the product of an undirected process such as natural selection acting on random variations. Creationism is focused on defending a literal reading of the Genesis account, usually including the creation of the earth by the Biblical God a few thousand years ago. Unlike creationism, the scientific theory of intelligent design is agnostic regarding the source of design and has no commitment to defending Genesis, the Bible or any other sacred text. Why, then, do some Darwinists keep trying to conflate intelligent design with creationism? It is a rhetorical strategy on the part of Darwinists who wish to delegitimize design theory without actually addressing the merits of its case. For more information read Center Director Stephen Meyer's piece "Intelligent Design is not Creationism" that appeared in The Daily Telegraph (London) or Center Associate Director's piece "Intelligent Design and Creationism Just Aren't the Same" in Research News & Opportunities.

Slabaugh responded by citing a description of intelligent design offered by the anti-ID National Academy of Sciences. The description repeatedly described intelligent design as creationist but never bothered to define the term. I countered with the definition of intelligent design provided by intelligent design proponents themselves (who presumably should have the right to define their own theory). Slabaugh then responded by citing Judge Jones's ruling in Kitzmiller v. Dover that intelligent design is tantamount to creationism (yes, Judge "Cut and Paste" Jones, who copied more than 90% of his decision virtually verbatim from plaintiffs' legal briefs, right down to the factual errors).

It seems strange to me that a reporter looks to the critics of intelligent design as neutral and authoritative sources for what intelligent design proponents believe. Would a reporter rely on a pro-life group to supply an impartial description of Planned Parenthood? Or a group of conservative medical doctors to supply a neutral description of Obamacare?

I do not want to be too hard on Mr. Slabaugh. Although clearly hostile toward intelligent design, he has quoted Discovery Institute accurately in his coverage of the intelligent design dispute at Ball State University. That is a lot more than can be said about many reporters. However, his false stereotyping of Discovery Institute as "pro-creationism" was unworthy of him; and his unwillingness to acknowledge and correct the error was frustrating.

Thinking that we might be talking past each other, I decided to ask Slabaugh a question:

Would you please provide me with your definition of creationism? Presumably you have a definition since you are using the term in your stories. I would like to be able to report this in our coverage of your reporting on Evolution News & Views.

In our subsequent correspondence, I asked Slabaugh to answer this question no fewer than three times. Each time he basically avoided answering it. I suspect he was becoming increasingly exasperated with me in the process. He finally wrote:

I've answered your question. I'm sorry you don't like the answer.  

In fact, he hadn't answered my question. So I tried one last time:

Actually, you haven't answered my question, and I don't understand why. You haven't told me your definition of creationism. You simply keep citing people who claim that intelligent design is creationism. OK, I get that -- I understand that you are calling ID creationism because you've decided to repeat as a neutral description other people's claims that ID is creationism. I disagree with what you've done, and I think it's unfair; but I understand it. However, that doesn't tell me what you think creationism itself is. It seems to me that asking for your definition of creationism is not an unreasonable request, especially since you seem intent on applying this label to intelligent design proponents and Discovery Institute.

Although you may not think so, I am actually trying to understand your position. But you are making it hard for me to do so!

Slabaugh then responded:

I'm not a dictionary. My personal opinion is creationism is a belief that supernatural forces are responsible for the origin and/or evolution of the universe, as opposed to it originating by accident or chance.

I appreciate Slabaugh's honesty, and his final willingness to provide his own definition of creationism. I thanked him for his answer, but I also asked him to think about the following: His definition of creationism basically counts as a "creationist" any traditional monotheist (Protestant, Catholic, Jewish, or Muslim). This includes the Christian scientists who say they accept modern evolutionary theory -- e.g., geneticist Francis Collins, physicist and Nobel laureate Charles Townes, and Harvard astronomer Owen Gingerich. It includes the Catholic priest and physicist who first proposed the Big Bang. It includes those who read Genesis metaphorically along with those who read it literally. And it includes about 90% of the American public.

As I explained to Slabaugh, it seems to me that any definition of creationism that lumps together so many divergent viewpoints spreads a lot more confusion than clarity. This is especially the case when the term "creationist" is commonly understood and applied by most people -- including most reporters -- in a much narrower manner. In my experience, when most people refer to "creationists" they mean Biblical literalists who think the earth was created in seven 24-hour days a few thousand years ago. A few people may also include old-earth creationists who who think the days of Genesis were lengthy periods. But rarely does someone define "creationist" to mean pretty much anyone who happens to believe in God. When a reporter uses the term in this idiosyncratic way without any explanation, I think he is engaging in stereotyping, not promoting understanding. And frankly, such an all-encompassing definition of "creationism" makes the term pretty useless and un-illuminating as a descriptor.

I also pointed out to Slabaugh that the modern theory of intelligent design does not actually claim that science can determine whether the intelligent cause active in nature is supernatural or natural. This has been a key point made by leading intelligent design proponents like Michael Behe and William Dembski since the 1990s. Intelligent design can be used as part of a larger argument for the existence of God (just as unguided evolutionary theory can be used as part of a larger argument that God is a "delusion"), but the modern scientific theory of intelligent design on its own is not an argument for the existence of God. It requires additional arguments from philosophy, history, and other disciplines to make that case.

The really discouraging thing here is not that reporters are critical of intelligent design. It is that so many of them apparently see nothing wrong with preventing intelligent design proponents from defining their own position. This is a very strange way to do journalism, and if journalists started to apply their approach to intelligent design to other topics, I think it would become manifestly clear how unfair it is. Imagine, for example, a journalist deciding to use "Marxist" as a neutral label for President Obama based on the views of certain right-wing academics and political activists. Would that be regarded as fair or impartial by most journalists? Of course not. What if a reporter redefined Marxist to mean anyone who supports more active government? Would that make applying the term to Obama in a news story more defensible? Hardly. Yet when reporters label intelligent design proponents "creationists," they are essentially doing the same thing.

What is really going on here is censorship. When reporters use as a "neutral" description of intelligent design a polemical smear invented by its critics, they are effectively silencing intelligent design proponents by not allowing them to speak for themselves. They are poisoning the well so no one will be willing to listen to the actual views expressed by intelligent design proponents. Journalists who write about intelligent design should re-read the Society of Professional Journalists' Code of Ethics, especially the provisions calling for them to "Support the open exchange of views, even views they find repugnant" and to "Give voice to the voiceless...."

Whatever a news reporter's views on intelligent design, he or she has a professional duty not to simply spread stereotypes and caricatures. That duty means nothing if it only applies to news coverage of groups and positions with which the reporter agrees. The real test of fairness for reporters is how they treat those with whom they disagree. When it comes to intelligent design, sadly, many reporters are failing the test.

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More Darwinian Degradation: Much Ado about Yeast

Michael Behe January 23, 2012 

Recently a paper by Ratcliff et al. (2012) entitled "Experimental evolution of mulitcellularity" appeared and received a fair amount of press attention, including a story in the New York Times. The authors discuss their results in terms of the origin of multicellularity on earth.

The senior author of the paper is Michael Travisano of the University of Minnesota, who was a student of Richard Lenski's in the 1990s. The paper, published in PNAS, was edited by Lenski. The gist is as follows.

The authors repeated three steps multiple times: 1) they grew single-celled yeast in a flask; 2) briefly centrifuged it; and 3) took a small amount from the bottom of the flask to seed a new culture. This selected for cells that sedimented faster than most. After a number of rounds of selection the cells sedimented much faster than the beginning cells. Examination showed that the fast-sedimenting cells formed clusters due to incomplete separation of replicating mother-daughter cells.

The cell clusters also were 10% less fit (that's quite an amount) than the beginning cells in the absence of the sedimentation selection. After further selection it was seen that some cells in clusters would "commit suicide" (apoptosis), which apparently made the clusters more brittle and allowed chunks to break off and form new clusters. (The beginning cells already had the ability to undergo apoptosis.)

It seems to me that Richard Lenski, who knows how to get the most publicity out of exceedingly modest laboratory results, has taught his student well. In fact, the results can be regarded as the loss of two pre-existing abilities: 1) the loss of the ability to separate from the mother cell during cell division; and 2) the loss of control of apoptosis.

The authors did not analyze the genetic changes that occurred in the cells, but I strongly suspect that if and when they do, they'll discover that functioning genes or regulatory regions were broken or degraded. This would be just one more example of evolution by loss of pre-existing systems, at which we already knew that Darwinian processes excel. The apparently insurmountable problem for Darwinism is to build new systems.

Literature Cited

Ratcliff, W. C., R. F. Denison, M. Borrello, and M. Travisano, 2012 Experimental evolution of multicellularity. Proc. Natl. Acad. Sci. USA doi/10.1073/pnas.1115323109

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Complexity by Subtraction Was Weird Enough; Now, Complexity by Harmful Mutations

Evolution News & Views September 2, 2013 

Get ready for a tale stranger than "Complexity by Subtraction." According to Nietzsche's famous maxim, "What does not kill me makes me stronger." That might be a good motto for a guy training for the Tough Mudder, but will it work in a bacterial cell or in a dinosaur trying to evolve flight? A paper in PNAS by Richard Lenski and his colleagues Arthur Covert III, Claus Wilke and Charles Ofria, "Experiments on the role of deleterious mutations as stepping stones in adaptive evolution," seeks to cast evolution as kind of a trampoline: organisms can bounce higher by jumping off the fitness peak (sometimes). Could it be true?

Deleterious mutations are just that: random changes that cause harm. Remember, the bacterium or other organism is not a Navy Seal running an obstacle course to get stronger by will and determination. No; its genome just got hit by a bullet. It's going down in flames. What must happen for Lenski's idea to gain traction is that a beneficial mutation, like a midair rescue helicopter, has to show up just in time -- and not only that, but take the creature up to a higher fitness peak. We read:

It might seem obvious that deleterious mutations must impede evolution. However, a later mutation may interact with a deleterious predecessor, facilitating otherwise inaccessible adaptations. Although such interactions have been reported before, it is unclear whether they are rare and inconsequential or, alternatively, are important for sustaining adaptation. We studied digital organisms  -- computer programs that replicate and evolve  -- to compare adaptation in populations where deleterious mutations were disallowed with unrestricted controls. Control populations achieved higher fitness values because some deleterious mutations acted as stepping stones across otherwise impassable fitness valleys. Deleterious mutations can thus sometimes play a constructive role in adaptive evolution. (Emphasis added.)

It might seem obvious, indeed, to anyone except a Darwinian evolutionist. Another maxim (not from Nietzsche) applies here: "If something sounds too good to be true, it probably is." There's good reason to be suspicious. This magic trick only worked in the computer. Computers are notoriously guided by programmers who would be happy to see a favored notion confirmed. In this case, there would be no PNAS paper, or funding, if it didn't work.

But Covert et al. already knew evolution is in a bind. In Sewall Wright's old "fitness landscape" scenario, organisms can get stuck on a "fitness peak" and never evolve higher. Crossing to a higher peak requires losing fitness in the valley between, where the organism will likely die. For years, evolutionists have worried about the ability of relaxed selection, neutral mutations or other mechanisms to get organisms across the valleys. These evolutionists from Michigan State and University of Texas were basically looking for new ways to help them get down so they could go up higher.

We know that humans, with intelligent planning, can go down to go up. They will risk running through fire or diving deep in water to get out of a bind. Sometimes the way out is through. Humans are very good at hurting themselves to achieve greater good in the long run: rigorous training, tearing down muscle to build it up stronger. We know all about that; but what does a bacterium, yeast cell or plant know? It knows nothing. It has no goals in mind. A deleterious mutation, if not outright lethal, will take its toll. What are the chances a beneficial "rescuing" mutation will happen along before purifying selection weeds out the unfit? If that is rare, how much rarer to get a beneficial mutation that joins forces with the deleterious mutation to make things better!

If your research goal is to prove this "could" happen, you can certainly program a computer to get it to happen. That's what these scientists did. They had a lot of faith in the potential of deleterious mutations:

Although such mutations are expected to be rare, new detrimental mutations are constantly generated, thus providing a multitude of potential stepping stones.

Ah, "potential" stepping-stones. They're all over the place! Throw rocks randomly into the lake; some of them could become potential stepping-stones. This is already sounding crazy.

Avida Again

It's unsurprising to learn that Lenski & Co. have resorted to a favorite magic kit, the evolutionary Avida program, written by philosopher Robert T. Pennock, author of the anti-ID book Tower of Babel. We've discussed this and similar algorithms many times.

Whether the "digital organisms" generated by such programs have any connection to the real world is highly unlikely, especially when human beings are rewarding them by design. The digital organisms live as long as the programmers let them. They don't have to find food. They don't have to endure the slings and arrows of outrageous fortune. Anyway, what does a logic routine in a computer have to do with building a trilobite?

Hands-On Evolution

A reading of the paper reveals investigator interference all over the place: e.g., "we disallowed double mutations to facilitate classifying each mutation as beneficial, neutral, deleterious, or lethal," they say in one place. Continuing:

Before a mutant offspring was placed into the population, its fitness was evaluated in an isolated test environment, thus taking advantage of an opportunity that exists in a computational realm but not in a biological one, namely, to measure the effect of a mutation before it impacts a population's evolution.

Convenient as this might have been for setting up this team's research, things don't work that way in the real world. Organisms respond holistically to all the influences acting them at the time. Fitness (whatever that slippery word means) in an "isolated test environment" might have nothing to do with fitness in the real world.

Tautalogy Again

Sometimes when wading through a paper like this it's helpful to jump ahead to the "Materials and Methods" section. If there's a procedural or logical flaw there, the paper is only going to arrive at a credible conclusion by sheer dumb luck.

How the did this research measure fitness? By the ability to survive and reproduce. How were the fake organisms able to survive and reproduce? Well, obviously, if they were the fit ones. Whenever fitness is defined in terms of survival, it collapses into a tautology: survivors survive because of the fitness of the fit. Here it is, under "Measuring the Fitness of Digital Organisms."

In the isolated test environment, and with additional mutations prevented, we evaluated each candidate mutant's fitness by allowing it to execute its genome. We measured two aspects of its performance: the rate at which it acquired SIPs (single-instruction processing units) and the number of instructions executed to replicate itself. The ratio of these two numbers is a close approximation to the organism's absolute fitness. If digital organism A has twice the fitness of organism B, then A will, on average, produce twice as many offspring as B in the same amount of time.

Moreover, the fit ones only showed up because the investigators prevented their death. Look at this from the Materials and Methods:

We disallowed mutations that produced unstable genotypes in all treatments, including the control treatment, because our analyses were predicated on single mutations occurring in genomes of constant length.

Too Little, Too Slow

In Chapter 10 of Darwin's Doubt, citing the work of Douglas Axe, Stephen Meyer shows that a probabilistic abyss lies between the zone of function of one protein and that of another. Degrading a functional protein leads to catastrophic loss of function. Repair systems quickly degrade nonfunctional proteins. Those that escape are eliminated by natural selection.
Initially glad to see that some deleterious mutations were rescued by subsequent beneficial ones, Lenski & Co. thought that if a little is good, more must be better. Look at this astonishing paragraph from the paper: they were "surprised" that adding more mutations didn't produce more fitness!

We were more surprised, however, that, at higher mutation rates, the use of stepping stones did not produce a measurable increase in final fitness. Previous theoretical studies have implicitly assumed that the rate of compensatory adaptation increases with the mutation rate. In that case, one would expect that deleterious mutations would be more important at higher mutation rate than at lower rates. One possible explanation for this unexpected result is that higher mutation rates drive populations toward flatter areas of the fitness landscape, with a greater proportion of mutations being neutral and thus fewer opportunities for compensatory changes. Further work will be necessary to determine whether this explanation is correct.

Only a Darwinian evolutionist could expect that shooting more random bullets into a complex system would improve it.

The Analogy Breaks Down

In Avida, the fitness of digital organisms is measured in terms of logic functions. Life, though, revolves around genes and proteins. There's no comparison. For one thing, the information content of the typical gene or protein is vastly greater than the information content of an "AND" or "NAND" or "EQU" logic gate. Proteins typically include hundreds of precisely sequenced amino acids, coded for by equal numbers of genetic alphabet letters (150 amino acids is a relatively small protein).

Moreover, a polypeptide sequence has to fold into a functional shape. A precisely ordered sequence is not enough. Without a stable fold, the polypeptide is useless, if not harmful. Just a few mutations to a working protein are often enough to destabilize the fold. An unstable protein will be targeted by proteases and destroyed; those that are not will be eliminated by "purifying selection." This has the effect of making the walls of a fitness peak steeper, and the valley deeper -- more like a cliff on the edge of an ocean filled with sharks.

In one of their experiments, the team tried to model sexual reproduction by having offspring garner bits from two "parents." Unfortunately, there was no benefit:

Given the role of deleterious mutations as stepping stones in long-term adaptation, one might then imagine that sexual populations should evolve higher fitness than asexual ones because sexual populations experience more of these potential stepping stones. However, we found no evidence of such an effect; sexual and asexual populations in the control treatments achieved comparable final fitness values (P = 0.6124, Mann-Whitney test). Thus, any potential benefits of sexual reproduction were offset by costs, including the disruption of beneficial interactions between mutations.

So even the most generous review of their work could only say it might have some applicability to microbes, but not to Cambrian animals, orchids, or humans.

How Lenski's contrived world of digital organisms inside a computer can have any relevance to living organisms is beyond imagining. Darwinian evolution only works when designers program a computer to make it work. Naturally, Lenski's lab ignored the critique of Avida published in an IEEE paper in 2009 by Ewert, Dembski and Marks.

Readers of Darwin's Doubt know that the problem for evolutionists lies not in finding isolated beneficial mutations, but in building whole new cell types, tissues, organs, body plans, and epigenetic information in one fell swoop, as seems to have happened in the Cambrian explosion. Meyer compares the unguided search for functional "stepping-stones" across the abyss with trying to traverse an ocean the size of our galaxy (p. 204).

Taxpayers, in case you were curious, can thank the National Science Foundation for funding Lenski's decade-long computer game.

Image credit: Thinh H/Flickr.

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The Spliceosome: A Dynamic Ribonucleoprotein Machine

Jonathan M. September 10, 2013 

The spliceosome has been described as one of "the most complex macromolecular machines known," "composed of as many as 300 distinct proteins and five RNAs" (Nilsen, 2003). The animation above reveals this astonishing machine at work on the precursor mRNA, cutting out the non-coding introns and splicing together the protein-coding exons.

Introns (which, unlike exons, do not code for proteins) can be of considerable length in higher eukaryotes, even spanning many thousands of bases and sometimes comprising some 90% of the precursor mRNA. In contrast, lower eukaryotes such as yeast possess fewer and shorter introns, which are typically fewer than 300 bases in length. Since introns are the non-coding segments of genes, they are removed from the mRNA before it is translated into a protein. This is not to say, of course, that introns are without important function in the cell (as I discuss here).

Comprising the spliceosome, shown at right (excerpted from Frankenstein et al., 2012)^[1] are several small nuclear ribonucleoproteins (snRNPs) -- called U1, U2, U4, U5 and U6 -- each of which contains an RNA known as an snRNA (typically 100-300 nucleotides in length) -- and many other proteins that each contribute to the process of splicing by recognizing sequences in the mRNA or promoting rearrangements in spliceosome conformation. The spliceosome catalyzes a reaction that results in intron removal and the "gluing" together of the protein-coding exons.

RNA Splicing

The first stage in RNA splicing is recognition by the spliceosome of splice sites between introns and exons. Key to this process are short sequence motifs. These include the 5' and 3' splice sites (typically a GU and AG sequence respectively); the branch point sequence (which contains a conserved adenosine important to intron removal); and the polypyrimidine tract (which is thought to recruit factors to the branch point sequence and 3' splice site). These sequence motifs are represented in the illustration below:

The U1 snRNP recognizes and binds to the 5' splice site. The branch point sequence is identified and bound by the branch-point-binding protein (BBP). The 3' splice site and polypyrimidine tract are recognized and bound by two specific components of a protein complex called U2 auxiliary factor (U2AF): U2AF35 and U2AF65 respectively.

Once these initial components have bound to their respective targets, the rest of the spliceosome assembles around them. Some of the previously bound components are displaced at this stage: For instance, the BBP is displaced by the U2 snRNP, and the U2AF complex is displaced by a complex of U4-U5-U6 snRNPs. The U1 and U4 snRNPs are also released. The first transesterification reaction then takes place, and a cut is made at the 5' splice site and the 5' end of the intron is subsequently connected to the conserved adenine found in the branch point sequence, forming the so-called "lariat" structure. This is followed by the second transesterification reaction which results in the splicing together of the two flanking exons. See this page for a helpful animation of the splicing process.

Other Important Protein Factors

Many other proteins play crucial roles in the RNA splicing process. One essential component is PRP8, a large protein that is located near the catalytic core of the spliceosome and that is involved in a number of critical molecular rearrangements that take place at the active site (for a review, see Grainger and Beggs, 2005). What is interesting is that this protein, though absolutely crucial to the RNA splicing machinery, bears no obvious homology to other known proteins.

The SR proteins, characterized by their serine/arginine dipeptide repeats and which are also essential, bind to the pre-mRNA and recruit other spliceosome components to the splice sites (Lin and Fu, 2007). SR proteins can be modified depending on the level of phosphorylation at their serine residues, and modulation of this phosphorylation helps to regulate their activity, and thus coordinate the splicing process (Saitoh et al., 2012; Plocinik et al., 2011; Zhong et al., 2009; Misteli et al., 1998). The illustration above (from here) shows the binding of SR proteins to splicing enhancer sites, which promotes the binding of U1 snRNP to the 5' splice site, and U2AF protein to the polypyrimidine tract and 3' splice site.

There are also ATPases that promote the structural rearrangements of snRNAs and release by the spliceosome of mRNA and the intron lariat. It is even thought that ATP-dependent RNA helicases play a significant role in "proofreading" of the chosen splice site, thus preventing the potentially catastrophic consequences of incorrect splicing (Yang et al., 2013; Semlow and Staley, 2012; Egecioglu and Chanfreau, 2011).

The Exon Junction Complex

The exon junction complex (EJC) is a protein complex comprised of several protein components (RNPS1, Y14, SRm160, Aly/REF and Magoh) left behind near splice junctions by the splicing process (Hir and Andersen, 2008). Their function is to mark the transcript as processed, and thus ready for export from the nucleus to the cytoplasm, and translation at the ribosome. The EJC is typically found 20 to 24 nucleotides upstream of the splice junction.

The EJC also plays an important role in nonsense mediated decay, a surveillance system used in eukaryotes to destroy transcripts containing premature stop codons (Trinkle-Mulcahy et al., 2009; Chang et al., 2007; Gehring et al., 2005). Upon encountering an EJC during translation, the ribosome displaces the complex from the mRNA. The ribosome then continues until it reaches a stop codon. If, however, the mRNA contains a stop codon before the EJC, the nonsense mediated decay pathway is triggered. The EJC and its position thus contribute to transcript quality control.

The Evolution of the Spliceosome

A popular hypothesis regarding the origins of the spliceosome is that its predecessor was self-splicing RNA introns (e.g. Valadkhan, 2007). Such a hypothesis makes sense of several observations. For example, a simpler way to achieve splicing presumably would be to bring the splice sites together in one step to directly cleave and rejoin them. The proposed scenario, however, would explain the use of a lariat intermediate, since a lariat is generated by group II RNA intron sequences (Lambowitz1 and Zimmerly, 2011;Vogel and Borner, 2002).

The hypothesis also helps to clarify why RNA molecules play such an important part in the splicing process. Examples of self-splicing RNA introns still exist today (e.g., in the nuclear rRNA genes of the ciliate Tetrahymena) (Hagen and Cech, 1999; Price et al., 1995; Price and Cech, 1988; Kruger et al., 1982).

These observations may be taken as evidence as to the spliceosome's evolutionary predecessor, but they are hardly helpful in elucidating a plausible scenario for transitioning from one to the other. The spliceosome machinery is far more complex and sophisticated than autocatalytic ribozymes, involving not just five RNAs but hundreds of proteins.

Conclusion

The spliceosome is truly one of the most remarkable molecular machines in the cell. My purpose here was only to offer readers a small glimpse of this elegant work of nanotechnology, leaving out, of course, much important detail. As I venture deeper and deeper into the hidden world of the cell, the more I am filled with a tremendous sense of awe at the sheer genius and beauty of the design. If such engineering sophistication were encountered in any other realm of inquiry, it would immediately be attributed to intelligence. If biological systems give every appearance of having been designed, are we not justified -- in the absence of a viable alternative explanation -- in inferring that they most likely are the product of design?

Notes:

[1] Reprinted from Structure Volume 20, Issue 6. Ziv Frankenstein, Joseph Sperling, Ruth Sperling, Miriam Eisenstein. A Unique Spatial Arrangement of the snRNPs within the Native Spliceosome Emerges from In Silico Studies. Pages 1097-1106. Copyright (2012), with permission from Elsevier.

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