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Author Topic:   Nature's Engines and Engineering
Genomicus
Member (Idle past 1942 days)
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Message 1 of 2 (668319)
07-19-2012 6:52 PM


Nature’s Engines and Engineering
Introduction
In the past few decades, extensive biochemical research has revealed the cell to possess a remarkable array of molecular machines, from flagella to replisomes to ATP synthases. These machines are machines in a very real sense: they are composed of discrete protein components that interact with each other because of some input (e.g., energy in the form of ATP), thereby producing biological function. Indeed, the only real difference between molecular machines in the cell and man-made machines is that the former self-assemble.
How did these biological molecular machines originate? It is thought by most biologists that these machines evolved through a Darwinian pathway, with pre-cursor protein components being co-opted into new roles and associating with other proteins, gradually adding to the complexity of the system. Gene duplication, scaffolding, and other mechanisms would also play a pivotal role in the origin of these machines. Yet we can take another approach to this and hypothesize that some of the molecular machines in the cell are the products of engineering, and thus planning is behind their origin. This is the position of many intelligent design (ID) proponents, such as Michael Behe. Unfortunately, however, the ID community, for the most part, has contented itself with merely attacking the Darwinian explanation instead of developing a working design hypothesis. In short, although we see much material on why molecular machines could not have plausibly evolved, we see precious little on how they could have been designed. This is a potentially fatal flaw in the ID movement, because if it is to convince the scientific community at large that certain biological systems were engineered, then a testable design hypothesis is needed. This, in turn, would allow predictions to be made, and the model could thereby be falsified or confirmed. Formulating a novel design hypothesis is not easy, for it involves looking at current data in a new light, and one that would generate testable predictions. Nevertheless, in this short essay I have endeavored to lay out my ideas for a working design hypothesis on the engineering of molecular machines.
Background Considerations
The intelligent design/evolution discussion has somewhat ignored the historical nature of biological origins. By this I mean that ID proponents have focused on demonstrating that biological system X could not have evolved through Darwinian mechanisms, instead of asking the simple question: did biological system X actually evolve or was it intelligently designed? In other words, the discussion over biological origins has essentially become a question of plausibility, rather than a question of what actually happened. Biological system X could plausibly evolve but this does not mean that it did. The human mind is quite capable of imagining very creative non-teleological scenarios for the origin of any biological system, and we have to take this into account when considering the origin of a given biological system. A statement of plausibility says little about what actually happened in the history of a system, and thus independent evidence is needed to support any conclusion, be it non-teleological or teleological. We need to emphasize the historical nature of biological origins and instead of endlessly arguing over the plausibility (or lack thereof) of evolutionary mechanisms, we should try to determine what actually happened in the past.
There is one more point I wish to discuss before moving on. Intelligent design of molecular machines can be accomplished through direct design and through indirect design, which is front-loading. If a molecular machine is front-loaded, then it has a planned origin, but the design is indirect in that evolution is used to carry out the design objective. On the other hand, if a molecular machine is designed through direct engineering — e.g., through the de novo design of protein molecules — then we have an example of direct design. The hypothesis I will describe here is one of direct design.
The Design Hypothesis
As stated previously, biological machines are assembled from protein components. I propose that the components of molecular machines were engineered through the strategy of rational design, similar to the method humans use to design proteins. This, then, is the mechanism behind the construction of molecular machines (in this essay, whenever the term design hypothesis is used, I am referring exclusively to the above concept). Naturally, at the fundamental level, protein design is carried out through the intelligent manipulation of DNA sequences. Our current technology already allows the design of novel protein folds using computational methods (see, e.g., [1]). A key aspect of protein design is the modification of an already existing structure/sequence — if a protein structure can be modified such that it possesses a new function, an entirely novel protein fold does not need to be designed. Thus, under the design hypothesis described here, similarities among components in different biological machines is the result of a basic protein structure/sequence being re-used in different contexts. An example may be used here to clarify the above statement.
Consider the bacterial flagellum. A number of its protein components share significant similarity with non-flagellar proteins. For example, FliG is similar to MgtE [2], a magnesium transporter. Under the Darwinian model, this similarity is attributed to common descent: in the distant past, an MgtE copy was co-opted into the primitive bacterial flagellum and evolved into FliG. However, if the bacterial flagellar components were engineered, then this similarity is the result of MgtE being re-designed into FliG. More specifically, the protein sequence of MgtE would be tweaked in just the right way such that it would acquire the specific properties necessary for functioning in the bacterial flagellum. At first glance, all of this might seem obvious and possibly ad hoc. Yet it is this part of the hypothesis that I think is the most readily testable. To explore why this might be the case, we need to first take a look at things from a Darwinian perspective.
Molecular Clocks and the Evolution of Biological Machines
How can we distinguish actual homology among components from similarities that are the result of re-engineering a basic component for use in different systems? I suggest that the answer lies in molecular clocks. Molecular clocks allow us to estimate the time of divergence between protein/DNA sequences. For example, a molecular clock using cytochrome c sequences indicates that mammals and reptiles diverged approximately 300 million years ago [3], which correlates well with the fossil evidence. To understand how molecular clocks are useful for detecting engineering in molecular machine components, let us return to the bacterial flagellum.
In 2003, Nicholas Matzke proposed an evolutionary pathway for the origin of the bacterial flagellum [4]. This model begins with a passive pore being converted to an active pore through the association of the pore with an ATP synthase complex. It proposes that an ATP synthase was co-opted in toto early in the evolution of the flagellum. This was followed by a number of co-option events, such as the co-option of the Tol-Pal system which evolved into the MotAB complex. Next, MgtE was integrated into the evolving flagellar system such that it eventually gave rise to FliG. Naturally, this is only a summary of some of the steps involved in Matzke’s scenario. What we see is that various ATP synthase proteins share similarities with the following flagellar components: FliH (similar to the ATP synthase components AtpFH), FliI (AtpD), and FliJ. Given that Matzke’s scenario involves the in toto co-option of an ATP synthase, from an evolutionary point of view we would expect that FliH, FliI, and FliJ all diverged from their ATP synthase homologs at the same time. We could test this expectation through the use of molecular clocks. Moreover, we would also predict that MotAB diverged from the Tol-Pal components after the divergence of FliHIJ from the ATP synthase proteins. Finally, molecular clocks should show that FliG split from MgtE after the FliHIJ/ATP synthase and Tol-Pal/MotAB divergences. Thus, if molecular clocks confirmed that this specific sequence of events occurred, the evolutionary hypothesis for the origin of the flagellum would be significantly strengthened, and furthermore, the design hypothesis would be considerably weakened. This is because the design hypothesis explains the similarities of flagellar parts with non-flagellar components as the result of re-engineering rather than common descent — and if these similarities are indeed the result of re-engineering we would not expect to see the specific sequence of divergence times for flagellar components and their homologs that we would predict under the evolutionary hypothesis. Thus, although we cannot tell the difference between re-engineering and common descent of a particular component — e.g., FliG — when looking at this in a broader context, and taking into consideration the divergence times of different components, we can in fact establish if the similarity among components is most likely the result of common descent. In brief, the evolutionary model for the origin of the flagellum makes a precise prediction regarding the pattern of divergence times for specific flagellar proteins and their non-flagellar counterparts (Figure 1). I suggest that the design hypothesis yields a different prediction, and one that the evolutionary model does not make.

Figure 1. The prediction of the evolutionary hypothesis regarding divergence times of flagellar components from their homologs. The red arrow represents the flow of time. We see that the evolutionary hypothesis predicts that FliHIJ originated prior to either MotAB or FliG. MotAB arose after FliHIJ but before FliG. Finally, FliG formed after FliHIJ and MotAB.

For this prediction that stems from the design hypothesis we must look again to molecular clocks, but this time with an interesting twist.
Molecular Clocks and the Design Hypothesis
Contrary to the Darwinian model, the design hypothesis explains the similarities of machine components to other proteins as the result of re-using a protein in different contexts. Now, if molecular machine components were engineered, what would molecular clocks tell us about the divergence times of the machine components and their analogs (note: since homology, by definition, refers to common descent, I am using the term analog when dealing with the design hypothesis; i.e., from a design perspective, FliG and MgtE are not homologs, but analogs)? It is important to understand that direct design involves directly engineering the components and assembling the machine, such that all components originate at the same time. This is entirely unlike the evolutionary model, wherein components originate and associate with each other in a step-by-step, gradual pathway over a comparatively long timeframe. At first glance, then, it would seem like the design hypothesis predicts that molecular clocks would show that all machine components arose at approximately the same time. But things are not so simple. It would be rare to re-use a protein in different functions but not modify the protein’s sequence and structure. For example, the amino acid sequence of MgtE would have to be tweaked until it could be integrated into the flagellar system. Without any modifications to MgtE, it is unlikely that it could function properly in the context of the flagellum. FliG is a highly specific protein, interacting with the MS-ring and the MotAB complex. Thus, re-using MgtE in the flagellum would almost certainly require that its sequence be modified. The same is true for MotAB and the Tol-Pal proteins. The Tol-Pal system does not rotate other protein complexes while MotAB is a key player in rotating the flagellar filament. As such, the Tol-Pal proteins would have to be re-engineered before they could be incorporated into the flagellum. All of this means that we cannot logically predict — from a design perspective — that molecular clocks will demonstrate that all machine components originated at about the same time. This is because if some proteins are modified more substantially than others, it would confuse the molecular clock. Protein components that have undergone more drastic modifications will have the appearance of being more ancient (using a molecular clock), while proteins that are only slightly changed will appear to have originated more recently. In particular, the design hypothesis predicts that molecular clocks will show that proteins with rapid substitution rates will have a later origin, while proteins with slow substitution rates will have an early origin. We can summarize this prediction in this manner: in general, the slower the substitution rate, the more ancient the protein will appear to be. If a protein has a slow substitution rate, then any modifications to the sequence of that protein will give the appearance of a large amount of time passing by. In contrast, even fairly extensive modifications to a protein with a rapid substitution rate will not significantly affect the molecular clock. To further refine this prediction, we can take into account the amount of modification that would be needed for a given protein (Figure 2).

Figure 2. Summary of the predictions of the design hypothesis described here.

For example, if protein X has a slow substitution rate, but we deduce that its analog would have to be significantly changed before it could function as protein X, then we would predict that it has an early-origin — according to molecular clocks (keep in mind that, under the design hypothesis, the components of the machine actually originated at the same time). A discussion on how we could determine the amount of re-engineering that would be necessary is beyond the scope of this essay, but such a task could probably be relatively easily accomplished.
Conclusion
Here, I have discussed a possible mechanism for biological intelligent design, and one that presents us with a falsifiable hypothesis. An important assumption of this hypothesis is that the engineer(s) were rational agents. Without this basic premise, we cannot make any predictions because one could argue that the designers were purposefully trying to deceive us and tampered with any evidence of their involvement. But if we ensure that only rational agents are part of our hypothesis, we can make testable predictions. Naturally, this assumption must go both ways — if we encounter irrationality in a biological system, this must count against the design hypothesis.
Thoughts?
References
1. Kuhlman B, Dantas G, Ireton GC, Varani G, Stoddard BL, Baker D., 2003. Design of a novel globular protein fold with atomic-level accuracy. Science. 302(5649):1364-8.
2. Pallen, M.J., Matzke, N.J., 2006. From the Origin of Species to the origin of bacterial flagella. Nat Rev Microbiol. 4, 784-790.
3. Dickerson, R.E., 1971. Sequence and structure homologies in bacterial and mammalian-type cytochromes. J Mol Biol. 57, 1-15.
4. Matzke, N.J., 2003. Evolution in (Brownian) space: a model for the origin of the bacterial flagellum, TalkDesign.
Edited by Genomicus, : No reason given.
Edited by Genomicus, : No reason given.
Edited by Genomicus, : No reason given.

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Message 2 of 2 (668340)
07-20-2012 2:25 AM


Thread Copied to Intelligent Design Forum
Thread copied to the Nature's Engines and Engineering thread in the Intelligent Design forum, this copy of the thread has been closed.

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