Understanding through Discussion


Welcome! You are not logged in. [ Login ]
EvC Forum active members: 109 (8803 total)
Current session began: 
Page Loaded: 11-23-2017 8:35 PM
398 online now:
Aussie, halibut, jar, LamarkNewAge, Phat (AdminPhat) (5 members, 393 visitors)
Chatting now:  Chat room empty
Newest Member: jaufre
Post Volume:
Total: 822,909 Year: 27,515/21,208 Month: 1,428/1,714 Week: 271/365 Day: 40/73 Hour: 4/0

Announcements: Reporting debate problems OR discussing moderation actions/inactions


Thread  Details

Email This Thread
Newer Topic | Older Topic
  
Author Topic:   Nature's Engines and Engineering
Genomicus
Member (Idle past 12 days)
Posts: 846
Joined: 02-15-2012


(1)
Message 1 of 15 (668339)
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.


Replies to this message:
 Message 4 by Dr Adequate, posted 07-20-2012 3:57 AM Genomicus has responded
 Message 5 by Tangle, posted 07-20-2012 4:15 AM Genomicus has responded
 Message 6 by Wounded King, posted 07-20-2012 6:38 AM Genomicus has responded

  
Adminnemooseus
Director
Posts: 3830
Joined: 09-26-2002


Message 2 of 15 (668341)
07-20-2012 2:25 AM


Thread Copied from Proposed New Topics Forum
Thread copied here from the Nature's Engines and Engineering thread in the Proposed New Topics forum.
    
Taq
Member
Posts: 7263
Joined: 03-06-2009
Member Rating: 3.7


(1)
Message 3 of 15 (668343)
07-20-2012 3:27 AM


Will be commenting on this later, but I wanted to take a moment and commend Genomicus for starting an absolutely awesome thread. I wish there were more ID supporters like you. Keep up the hard work. We really appreciate it.
Replies to this message:
 Message 7 by Genomicus, posted 07-20-2012 11:25 AM Taq has not yet responded

  
Dr Adequate
Member
Posts: 15972
Joined: 07-20-2006
Member Rating: 4.7


Message 4 of 15 (668345)
07-20-2012 3:57 AM
Reply to: Message 1 by Genomicus
07-19-2012 6:52 PM


Just to be clear ... is this different from your previous design hypothesis? Only in your last thread you seemed to be saying that analogues were in fact homologues derived from a common ancestor, in fact your argument seemed to depend on it. Are you now doing something else?

I'm still working on figuring out what your argument actually is, I'll comment on it when this becomes clear to me.


This message is a reply to:
 Message 1 by Genomicus, posted 07-19-2012 6:52 PM Genomicus has responded

Replies to this message:
 Message 8 by Genomicus, posted 07-20-2012 11:35 AM Dr Adequate has responded

  
Tangle
Member
Posts: 5164
From: UK
Joined: 10-07-2011
Member Rating: 2.5


Message 5 of 15 (668346)
07-20-2012 4:15 AM
Reply to: Message 1 by Genomicus
07-19-2012 6:52 PM


I need to rework this so I understand it.

To use the mousetrap analogy often quoted in early ID discussions, ID says that the trap couldn't evolve because without any one of its components - the base, the lever, the spring, the trigger - it wouldn't function. Ie it is irreducibly complex.

Evolution says that if each component had an earlier and independent useage, they could combine later to form a functioning trap. (And in the case of your flagella, those independent molecules have been found and ID was debunked.)

Consider an all metal trap made of carbon steel. A pure ID trap would have all the components - the base, trigger, lever, spring made at the same time so carbon dating the steel would produce the same date for all components.

If however, the trap evolved over time, each component would necessarily have differing dates.

OK so far?

The bit I'm struggling with is your added complexity of ID needing to rework previously built components in order to make the mousetrap. The lever doesn't quite fit the trigger so a new section of steel has to be welded in by the designer. This tweaking will contaminate the C dating of the part.

It seems to me that the designer interfering with the part is exactly the same as evolution interfereing with the part and will give the same result.

Or is my analogy incomplete/wrong?


Life, don't talk to me about life - Marvin the Paranoid Android

This message is a reply to:
 Message 1 by Genomicus, posted 07-19-2012 6:52 PM Genomicus has responded

Replies to this message:
 Message 9 by Genomicus, posted 07-20-2012 12:04 PM Tangle has responded

  
Wounded King
Member (Idle past 1688 days)
Posts: 4149
From: Edinburgh, Scotland
Joined: 04-09-2003


(1)
Message 6 of 15 (668351)
07-20-2012 6:38 AM
Reply to: Message 1 by Genomicus
07-19-2012 6:52 PM


Lets do Science!
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.

Interesting, so on reading this I said to myself "Self, there must be some sort of data on substitution rates in flagellar proteins out there." I went looking but only found a couple of papers from a few basic search terms. One paper, Toft and Fares (2008), was focused on looking at the degeneration and neofunctionalisation of flagellar proteins in bacteria that were endosymbionts. This wasn't particularly relevant in itself but one of the sets of data they collected included synonymous and non-synonymous substitution rates in both endosymbiotic and free living bacteria, see supplementary data.

Since it is protein evolution we are interested in I took the non-synonymous values for the free-living bacteria and ranked them. Sadly they only looked at the genes which were still present in the endosymbiotic bacteria so there was no data for MotA/B or for FliJ.

This very first glance approach doesn't look great for your theory; out of 510 genes they had data for FliG was 303rd in terms of non-synonymous substitution rate with a rate of 0.0208 substitutions per site compared to 0.0525 for FliI (ranked 123rd) and 0.1029 for FliH (ranked 19th).

*ABE* I found amino acid and DNA sequences for FliJ, MotA and MotB from E. coli and S. typhimurium and used the PAML software to find a dN value. The values were as follows, MotA: 0.0389; MotB:0.0538; FliJ:0.0633.

So going by the substitution rates from highest to lowest the order comes out as FliH, FliJ, MotB, FliI, MotA and finally FliG. This seems to be almost exactly the opposite of what your theory predicts. Obviously we are missing the second variable of how much modification was needed for each particular protein to adapt it from the original.*/ABE*

Of course these were values from only a couple of bacterial species, E. coli and Salmonella typhimurium, so a wider survey might well turn up different average rates. It shouldn't be impossible to extract the protein sequence for the 6 proteins from your example from the NCBI, in fact the difficult part would be deciding which species to restrict ourselves to since, for example, there are ~26,000 entries for MotA. Maybe we could choose a dozen or so commonly studied bacteria or follow a strategy like Liu and Ochman (2007) and take 1 species from each of the 11 large bacterial groupings they identify since they are all species with flagellar systems.

Do you think this would be a worthwhile project?

TTFN,

WK

Edited by Wounded King, : Added values for MotA, MotB and FliJ.


This message is a reply to:
 Message 1 by Genomicus, posted 07-19-2012 6:52 PM Genomicus has responded

Replies to this message:
 Message 11 by Genomicus, posted 07-20-2012 1:40 PM Wounded King has not yet responded
 Message 15 by Genomicus, posted 07-26-2012 11:05 AM Wounded King has not yet responded

    
Genomicus
Member (Idle past 12 days)
Posts: 846
Joined: 02-15-2012


Message 7 of 15 (668369)
07-20-2012 11:25 AM
Reply to: Message 3 by Taq
07-20-2012 3:27 AM


Will be commenting on this later, but I wanted to take a moment and commend Genomicus for starting an absolutely awesome thread. I wish there were more ID supporters like you. Keep up the hard work. We really appreciate it.

Thanks!


This message is a reply to:
 Message 3 by Taq, posted 07-20-2012 3:27 AM Taq has not yet responded

  
Genomicus
Member (Idle past 12 days)
Posts: 846
Joined: 02-15-2012


Message 8 of 15 (668371)
07-20-2012 11:35 AM
Reply to: Message 4 by Dr Adequate
07-20-2012 3:57 AM


Just to be clear ... is this different from your previous design hypothesis? Only in your last thread you seemed to be saying that analogues were in fact homologues derived from a common ancestor, in fact your argument seemed to depend on it. Are you now doing something else?

Yes. The previous design hypothesis I discussed was front-loading, which is indirect design. However, the two hypotheses I have discussed are not necessarily incompatible. Let me explain.

If you designed the bacterial flagellum into the initial cells, there's no need to front-load it into existence. Thus, under this view, the bacterial flagellum was engineered, but there's still plenty of room for front-loading. I'm trying to focus on a molecular machine that could have been in the first life forms because then you could have both direct engineering and front-loading.


This message is a reply to:
 Message 4 by Dr Adequate, posted 07-20-2012 3:57 AM Dr Adequate has responded

Replies to this message:
 Message 13 by Dr Adequate, posted 07-21-2012 10:01 AM Genomicus has responded

  
Genomicus
Member (Idle past 12 days)
Posts: 846
Joined: 02-15-2012


Message 9 of 15 (668372)
07-20-2012 12:04 PM
Reply to: Message 5 by Tangle
07-20-2012 4:15 AM


Hi Tangle,

To use the mousetrap analogy often quoted in early ID discussions, ID says that the trap couldn't evolve because without any one of its components - the base, the lever, the spring, the trigger - it wouldn't function. Ie it is irreducibly complex.

Evolution says that if each component had an earlier and independent useage, they could combine later to form a functioning trap. (And in the case of your flagella, those independent molecules have been found and ID was debunked [note: specifically, the argument that all flagellar components are unique was refuted].)

Consider an all metal trap made of carbon steel. A pure ID trap would have all the components - the base, trigger, lever, spring made at the same time so carbon dating the steel would produce the same date for all components.

If however, the trap evolved over time, each component would necessarily have differing dates.

OK so far?

Correct.

The bit I'm struggling with is your added complexity of ID needing to rework previously built components in order to make the mousetrap. The lever doesn't quite fit the trigger so a new section of steel has to be welded in by the designer. This tweaking will contaminate the C dating of the part.

Just to be clear, the engineers would need to tweak the analogs of flagellar components because they're re-using proteins that already exist but are not functioning in a flagellar context.

It seems to me that the designer interfering with the part is exactly the same as evolution interfereing with the part and will give the same result.

The difference is that under the evolutionary model the parts of the mousetrap originate at different points in time. Let's take a look at what the evolution of a mousetrap might look like.

The typical mousetrap has 5 parts:
1. Spring.
2. Hammer.
3. Hold-down bar.
4. Catch.
5. Platform.

(See here for details: http://udel.edu/~mcdonald/oldmousetrap.html).

The following pathway is invoked for the evolution of the mousetrap:

1.We begin with a one-part mousetrap consisting of only the platform. The platform has glue spread on it and this is able to catch mice. The platform may be initially just any ole' piece of wood that is polished and shaped so that it is smooth.

2. Next, a spring from an electronic device is co-opted and associates with the platform. The spring serves to function as both a primitive hammer and (obviously) a spring.

3. The hammer is borrowed from a wire and attached to the spring, increasing the efficiency of the original, primitive hammer.

4. A hold-down bar is likewise co-opted from another piece of wire.

5. Finally, a plastic catch is co-opted from some device.

We now have a five-part mousetrap. The evolutionary model would therefore predict that: the platform originated first, followed by the spring, the hammer, the hold-down bar, and finally the catch. Even if each of these parts need to be modified by evolution before they are functioning at full efficiency, the individual components are nonetheless originating in a specific sequence.

On the other hand, the engineering hypothesis predicts that each of the components originated at about the same time. The components that are borrowed would need to be tweaked before they can function efficiently in the overall system, and this would lead to the problem that the dating method would show that they did not originate at the same time. Thus, we'd need to work around this problem, and I described how the refined prediction for the design hypothesis looks like (see Figure 2 in the essay).

Edited by Genomicus, : No reason given.

Edited by Genomicus, : No reason given.


This message is a reply to:
 Message 5 by Tangle, posted 07-20-2012 4:15 AM Tangle has responded

Replies to this message:
 Message 10 by Tangle, posted 07-20-2012 12:29 PM Genomicus has responded

  
Tangle
Member
Posts: 5164
From: UK
Joined: 10-07-2011
Member Rating: 2.5


Message 10 of 15 (668375)
07-20-2012 12:29 PM
Reply to: Message 9 by Genomicus
07-20-2012 12:04 PM


Genomicus writes:

We now have a five-part mousetrap. The evolutionary model would therefore predict that: the platform originated first, followed by the spring, the hammer, the hold-down bar, and finally the catch. Even if each of these parts need to be modified by evolution before they are functioning at full efficiency, the individual components are nonetheless originating in a specific sequence.

This is my problem. At least in the mousetrap, the parts do not need to be produced in sequence. All the parts can be of the same age but be performing separate functions in other devices.

On the other hand, the engineering hypothesis predicts that each of the components originated at about the same time. The components that are borrowed would need to be tweaked before they can function efficiently in the overall system, and this would lead to the problem that the dating method would show that they did not originate at the same time. Thus, we'd need to work around this problem, and I described how the refined prediction for the design hypothesis looks like (see Figure 2 in the essay).

I think that you first need to show why evolution's parts need to be produced in sequence and show that they weren't doing different jobs elesewhere. (But that may be my ignorance of the developmental features of bacteria and where the mousetrap analogy fails)


Life, don't talk to me about life - Marvin the Paranoid Android

This message is a reply to:
 Message 9 by Genomicus, posted 07-20-2012 12:04 PM Genomicus has responded

Replies to this message:
 Message 12 by Genomicus, posted 07-20-2012 2:34 PM Tangle has not yet responded

  
Genomicus
Member (Idle past 12 days)
Posts: 846
Joined: 02-15-2012


Message 11 of 15 (668378)
07-20-2012 1:40 PM
Reply to: Message 6 by Wounded King
07-20-2012 6:38 AM


Re: Lets do Science!
Thank you Wounded King for taking the time to provide data on substitution rates for several flagellar proteins.

However, I disagree with this statement:

This very first glance approach doesn't look great for your theory; out of 510 genes they had data for FliG was 303rd in terms of non-synonymous substitution rate with a rate of 0.0208 substitutions per site compared to 0.0525 for FliI (ranked 123rd) and 0.1029 for FliH (ranked 19th).

I have no idea why you think that the fact that FliG has a slower substitution rate than FliH or FliI somehow falsifies the hypothesis.

I am equally puzzled by this:


I found amino acid and DNA sequences for FliJ, MotA and MotB from E. coli and S. typhimurium and used the PAML software to find a dN value. The values were as follows, MotA: 0.0389; MotB:0.0538; FliJ:0.0633.

So going by the substitution rates from highest to lowest the order comes out as FliH, FliJ, MotB, FliI, MotA and finally FliG. This seems to be almost exactly the opposite of what your theory predicts. Obviously we are missing the second variable of how much modification was needed for each particular protein to adapt it from the original.

But we are also missing the extremely important variable of a molecular clock estimate for the divergence times of each of these proteins from their analogs/homologs. I am really quite baffled as to why "going by the substitution rates from highest to lowest the order comes out as FliH, FliJ, MotB, FliI, MotA and finally FliG" is "almost exactly the opposite of what your theory predicts." Would you mind elaborating on that? Thanks.

Simply calculating the rates of substitutions for each of these proteins is not enough. It is very important that we carry out the harder task of estimating the divergence times for these proteins.

Maybe we're talking past each other though.

Of course these were values from only a couple of bacterial species, E. coli and Salmonella typhimurium, so a wider survey might well turn up different average rates. It shouldn't be impossible to extract the protein sequence for the 6 proteins from your example from the NCBI, in fact the difficult part would be deciding which species to restrict ourselves to since, for example, there are ~26,000 entries for MotA. Maybe we could choose a dozen or so commonly studied bacteria or follow a strategy like Liu and Ochman (2007) and take 1 species from each of the 11 large bacterial groupings they identify since they are all species with flagellar systems.

Do you think this would be a worthwhile project?

Yes. Naturally, estimating the divergence times of these proteins from their homologs (or analogs, depending on the context) would also make an interesting project.


This message is a reply to:
 Message 6 by Wounded King, posted 07-20-2012 6:38 AM Wounded King has not yet responded

  
Genomicus
Member (Idle past 12 days)
Posts: 846
Joined: 02-15-2012


Message 12 of 15 (668394)
07-20-2012 2:34 PM
Reply to: Message 10 by Tangle
07-20-2012 12:29 PM


I think that you first need to show why evolution's parts need to be produced in sequence and show that they weren't doing different jobs elesewhere. (But that may be my ignorance of the developmental features of bacteria and where the mousetrap analogy fails)

When it comes to molecular evolution, the mousetrap/carbon dating analogy breaks down. Look at it this way: as soon as a protein is co-opted into a new system with a new functional role, the molecular clock starts ticking. For example, as soon as an ATP synthase is co-opted into a passive pore, the molecular clock for those ATP synthase components starts to tick. It now belongs to a different "class" of ATP synthases, and one that is distinct from the "normal class" of ATP synthases. Thus, from an evolutionary point of view, the molecular clock should indeed reveal that the components of a given machine arose in a precise order. E.g., when it comes to the flagellum, the origin of the flagellar-specific ATP synthase should be earlier than the origin of FliG.


This message is a reply to:
 Message 10 by Tangle, posted 07-20-2012 12:29 PM Tangle has not yet responded

  
Dr Adequate
Member
Posts: 15972
Joined: 07-20-2006
Member Rating: 4.7


Message 13 of 15 (668450)
07-21-2012 10:01 AM
Reply to: Message 8 by Genomicus
07-20-2012 11:35 AM


Yes. The previous design hypothesis I discussed was front-loading, which is indirect design. However, the two hypotheses I have discussed are not necessarily incompatible. Let me explain.

If you designed the bacterial flagellum into the initial cells, there's no need to front-load it into existence. Thus, under this view, the bacterial flagellum was engineered, but there's still plenty of room for front-loading. I'm trying to focus on a molecular machine that could have been in the first life forms because then you could have both direct engineering and front-loading.

But doesn't this rather deprive your ideas of any predictive power? You can take any two things that look like homologues. You can see if the observations still fit your idea if they were actually analogues created In The Beginning. If the observations let you down, then no problem, you can just say: "oh, well then, they really are homologues; I said that that wasn't incompatible with my latest idea". Heads you win, tails you don't lose.

---

I hope to get round to the main substance of your OP ... soonish.

Edited by Dr Adequate, : No reason given.


This message is a reply to:
 Message 8 by Genomicus, posted 07-20-2012 11:35 AM Genomicus has responded

Replies to this message:
 Message 14 by Genomicus, posted 07-22-2012 12:43 PM Dr Adequate has not yet responded

  
Genomicus
Member (Idle past 12 days)
Posts: 846
Joined: 02-15-2012


Message 14 of 15 (668514)
07-22-2012 12:43 PM
Reply to: Message 13 by Dr Adequate
07-21-2012 10:01 AM


But doesn't this rather deprive your ideas of any predictive power? You can take any two things that look like homologues. You can see if the observations still fit your idea if they were actually analogues created In The Beginning. If the observations let you down, then no problem, you can just say: "oh, well then, they really are homologues; I said that that wasn't incompatible with my latest idea". Heads you win, tails you don't lose.

What isn't incompatible with my latest hypothesis is the idea that some machines are front-loaded - which would imply that their components were not directly designed - and other machines were directly engineered. However, if we hypothesize specifically that, for example, the bacterial flagellar components were engineered, but we find that in fact they share actual homology with precursor parts, then the specific hypothesis that the flagellum was engineered through rational design is falsified.


This message is a reply to:
 Message 13 by Dr Adequate, posted 07-21-2012 10:01 AM Dr Adequate has not yet responded

  
Genomicus
Member (Idle past 12 days)
Posts: 846
Joined: 02-15-2012


Message 15 of 15 (668996)
07-26-2012 11:05 AM
Reply to: Message 6 by Wounded King
07-20-2012 6:38 AM


Let's do Science: brief note to Wounded King
I'm not sure how I missed this in my previous response, but I'd like to point out that in Message 6 no substitution rates for flagellar proteins were provided:

Since it is protein evolution we are interested in I took the non-synonymous values for the free-living bacteria and ranked them. Sadly they only looked at the genes which were still present in the endosymbiotic bacteria so there was no data for MotA/B or for FliJ.

This very first glance approach doesn't look great for your theory; out of 510 genes they had data for FliG was 303rd in terms of non-synonymous substitution rate with a rate of 0.0208 substitutions per site compared to 0.0525 for FliI (ranked 123rd) and 0.1029 for FliH (ranked 19th).

I found amino acid and DNA sequences for FliJ, MotA and MotB from E. coli and S. typhimurium and used the PAML software to find a dN value. The values were as follows, MotA: 0.0389; MotB:0.0538; FliJ:0.0633.

So going by the substitution rates from highest to lowest the order comes out as FliH, FliJ, MotB, FliI, MotA and finally FliG. This seems to be almost exactly the opposite of what your theory predicts. Obviously we are missing the second variable of how much modification was needed for each particular protein to adapt it from the original.

However, there is a difference between estimating the number of nonsynonymous substitutions per site between a pair of sequences and calculating the substitution rate. Both the cited paper and the PAML values are dN values, not substitution rates. What's the difference? The number of nonsynonymous substitutions per site tells us how much two sequences differ. The substitution rate tells us the number of substitutions per site per year.

This hasn't been done for the above flagellar proteins, and you'll have to do that if you're going to have some data to falsify the hypothesis. After that, the very important step of calculating molecular clock estimates for the divergence times of flagellar proteins and their homologs would have to be done.


This message is a reply to:
 Message 6 by Wounded King, posted 07-20-2012 6:38 AM Wounded King has not yet responded

  
Newer Topic | Older Topic
Jump to:


Copyright 2001-2015 by EvC Forum, All Rights Reserved

™ Version 4.0 Beta
Innovative software from Qwixotic © 2017