A Teleological Hypothesis about a Machine

How is it that we can use a teleological perspective to guide research in the laboratory? Consider the basics of the scientific method: you make observations; the observations, in the context of background belief, lead to a tentative explanation called the hypothesis; the hypothesis is often then formed with the help of "if,then" logic that allows for testing; the results of the testing then can be viewed as supporting the hypothesis (positive evidence) or weakening (even refuting) the hypothesis (contrary evidence). In this case, I would argue that the initial observations used to infer the hypothesis do count as evidence. That is, hypotheses themselves are formed from evidence. The experimentation is simply an attempt to confirm the hypothesis with additional evidence (it also helps to ensure we are not arguing in a circle). Once enough evidence has been accumulated, the hypothesis becomes established and can then be used as part of a larger theory.

I have consistently stated that I view ID as a hypothesis. Thus, it builds on observations that function as evidence. For example, that life itself is built upon encoded information is an observation. That intelligent causation is closely matched to the origin of codes and information is also an observation. Thus, since life possesses an attribute closely correlated with intelligent design, a reasonable hypothesis is that life owes its origin to intelligent design.

At this point, one can begin to phrase the ID hypothesis in testable "if,-then" terms. Put simply, if life owes its origin to intelligent design, then high resolution studies will uncover further phenomena that echo origins through biomolecular engineering at the hands of rational agents.

One way to help us detect such bioengineering is through the use of Michael Behe's concept of Irreducible Complexity (IC). Since all machines demonstrate IC at some level, detecting IC is an important first step in detecting machinery. And as an added bonus, IC can help us gage the likelihood that non-teleological forces were behind the origin of such a machine (1,2)

 

The Degradosome

A recent article from Trends in Genetics (3) made the following observations:


The degradation of mRNA used to be viewed as an unsophisticated process in which a hodgepodge of ribonucleases attacked any accessible RNA. In contrast to mRNA, transfer and ribosomal RNAs were believed to be protected by their rapid folding into compact structures. This simplistic view has been made obsolete by the discovery of multiprotein machines with the capacity to unwind and degrade structured RNA.


One such multiprotein machine is the degradosome from E. coli. It can be viewed as a modular system composed of four parts: an exoribonuclease (PNPase), an endoribonuclease, an RNA helicase, and enolase. The apparent function of the degradosome is to serve as a universal RNA degradation machine (capable of digesting any RNA in the cell). There already seems to be suggestive evidence of its IC state (4).

First, three of the four components have interacting activities - endonuclease, exonuclease, helicase. These three functions may act in concert to degrade any RNA and are probably required to give the machine its universal functional role.

Secondly, biochemical tests support the importance of individual components:

  • PNPase by itself could not digest stem-loop structures, but when part of the degradosome, it functioned well.
  • If specific antibodies bind to the helicase, the degradosome did not digest the RNA.

Thus, it seems clear we have an IC complex here that depends on at least three protein components. However, the IC to ID inference is shaky here. This is because each of these three components could conceivably function independently or as part of another IC complex.

Thus, at this point, I would say this particular IC system does not clearly indicate ID. However, it does fit nicely into a view of front-loaded evolution. That is, if the degradosome represents an original state, things have been set up so that it would be easier to incorporate the three activities of the degradosome in different contexts. In other words, instead of viewing the origin of the degradosome as three separate activities that converged during history, it could be viewed as three coupled activities could split apart in history. One way to test for this is to determine how ancient this complex really is. Thus far, it has been identified and studied in E. coli. What about gram positives, for example?

But now we turn to the really fun part. What about enolase? No one knows what it is doing with the degradosome. No one expected to be associated with the degradosome, as it doesn't bind RNA. On the contrary, it's an enzyme that is part of glycolysis (a core metabolic pathway that breaks down glucose). But what is really interesting is that it catalyzes its glycolytic reaction just as well as its cytoplasmic counterparts. So let me be the first to propose a hypothesis for the function of enolase as part of this degradosome complex by using ID logic.

 

ID Sheds Light on Enolase

ID entails that these cellular processes are quite sophisticated. Consistent with this prediction is a quasi-solid state cell, where order is paramount and random processes are minimized. Science, on the other hand, is defined by its attempt to understand all biotic reality in purely non-teleological terms. Thus, it perceives the OOL as a series of very simple events building on each other to eventually create the complexity we call life. The result? It envision the first cells as rudimentary and sloppy entities. In contrast, I envision the OOL of life on this planet as a consequence of biomolecular engineering at the hands of some form of advanced intelligence. I envision the first cells as complex and sophisticated entities. And while the introduction of such cells were probably followed by a long history of evolution, I expect to find traces of such initial states because, as I have explained elsewhere, such a state is front-loaded and would be continually exploited by evolution.

So I will make a prediction about enolase function from this perspective.

First, IC critics might cite enolase as an example of an alternative function. Because of my interest in identifying and defining IC systems, as a function of my interest in ID, I took notice of this system and looked around. Without an interest in ID, degradosomal enolase would have been just one of those weird things in biology. As I began to think about enolase, in light of its lack of a role in RNA processing, I began to ask if this type of arrangement might reflect the sophisticated, machine-like context of the cell.

So let's add a few observations.


1. The helicase in the degradosome is ATP dependent.

2. Enolase, along with PNPase and the helicase, form a multimeric complex docked on the C-terminus of RnaseE (the endonuclease).

3. Experiments in other cells show that enolase can form high-affinity complexes with pyruvate kinase and phosphoglycerate mutase, the two enzymes that flank enolase on each side in the glycolytic pathway.

4. Pyruvate kinase carries out a reaction that forms ATP.


These observations, seen in the light of my ID perspective, lead to an obvious prediction about the function of enolase in the degradosome:

Enolase functions in the degradosome as a prong that plugs the degradosome into the glycolytic pathway so that ATP generated by pyruvate kinase is then quickly channeled to the helicase to fuel its unwinding activity.

That is, the degradosome is a dynamic modular machine that literally is plugged in to turn it on. But it can also easily be unplugged to turn it off, which is why scientists don't pull out other glycolytic enzymes attached to enolase. The reversible nature of degradosome function makes it possible to regulate its activity. The nice thing about this hypothesis is that it explains why enolase is still functioning as a glycolytic enzyme. But it also means enolase is not an example of an alternative function.

In fact, I recently came across an article which supports my prediction/model (6):


The Escherichia coli degradosome is a multienzyme complex with four major protein components: the endoribonuclease RNase E, the exoribonuclease PNPase, the RNA helicase RhlB and enolase. The first three of these proteins are known to have important functions in mRNA processing and degradation. In this work, we identify an additional component of the degradosome, polyphosphate kinase (PPK), which catalyses the reversible polymerization of the gamma-phosphate of ATP into polyphosphate (poly(P)). An E. coli strain deleted for the ppk gene showed increased stability of the ompA mRNA. Purified His-tagged PPK was shown to bind RNA, and RNA binding was prevented by hydrolysable ATP. Chemical modification of RNA by PPK, for example the addition or removal of 3' or 5' terminal phosphates, could not be detected. However, polyphosphate was found to inhibit RNA degradation by the degradosome in vitro. This inhibition was overcome by the addition of ADP, required for the degradation of polyphosphate and for the regeneration of ATP by PPK in the degradosome. Thus, PPK in the degradosome appears to maintain an appropriate microenvironment, removing inhibitory polyphosphate and NDPs and regenerating ATP.


This paper provided evidence that the degradosome is functioning in a specialized environment that is coupled to regulating ATP flux.

So there you have it. A specific prediction about the world of the cell from a teleological perspective. You heard it first and only here - on some obscure ID web page. So let's watch the literature for the developing story.

 

Recap

ID allows me to take a view of the cell more as a sophisticated, machine-like entity rather than a jury-rigged hodgepodge cobbled together by the Blind Watchmaker. This is because biomolecular engineering at the hands of an advanced intelligence is likely to express its intervention such that the products of design reflect a state that is elegantly coherent. The expectation of a jury-rigged hodgepodge makes more sense in light of non-teleological views, which begin with the random mess of the prebiotic soup and not the watch-type reality Paley once invoked.

So I begin to think that the degradosome could indeed reflect an originally designed state given its basic house-keeping role. If so, what is enolase doing there? A non-teleological view gives me no reason to expect a logical reason for it being there, as evolution doesn't have to be logical, in fact, it often simply jury-rigs hodgepodge things together. But if enolase was originally part of the degradosome, which in turn was originally designed, I expect a logical reason for it being there.

I then took notice of one glaring fact from the Nature paper cited below (4) - while enolase doesn't bind or alter RNA itself, it does still function as a glycolytic enzyme. As I began to think of a sophisticated, machine/factory-like state in the cytoplasm, it occurred to me that the helicase was ATP-dependent and enolase normally interacted with another enzyme that generates ATP. Now I typically envision ATP floating about and randomly becoming available to ATPases. But ID allowed me to lay this aside and consider that at least in this case, ATP could be funneled almost directly to the helicase as a consequence of its binding to enolase. This then led me to think of the degradosome as a regulated module which could literally be plugged in to an energy source (where the analogy to man-made machines was not missed by me). This then added to the logic of the system.

The Bottom Line

My prediction about degradosomal enolase function could turn out to be false. Or even if true, one might easily fit such a finding in a non-teleological view. But what matters is this example demonstrates a teleological approach CAN be used to guide lab research and, along the way, generate insight into the living world. Of course, I have previously demonstrated this with another topic(6), but with two concrete examples in hand, there is no reason to think ID can not be used to generate 3, 4, 5, etc. concrete examples. Thus, I would even go as far as to maintain the notion that ID is a "science stopper" or nothing more than a "god-of-the gaps" approach has been effectively refuted.

Citations 

 1. IC Debunked?

2. IC and Darwinian Pathways

3. Carpousis AJ, Vanzo NF, Raynal LC.  1999. mRNA degradation. A tale of poly(A) and multiprotein machines. Trends in Genetics 15: 24-28.

 

4. Py B, Higgins CF, Krisch HM, Carpousis AJ. A DEAD-box RNA helicase in the Escherichia coli RNA degradosome. Nature 1996 May 9;381(6578):169-172.

5. Blum E, Py B, Carpousis AJ, Higgins CF. Polyphosphate kinase is a component of the Escherichia coli RNA degradosome. Mol Microbiol 1997 Oct;26(2):387-398.

6. Using ID to Infer Molecular Events

[edited 5/5/05]

ID THINK