quote:
The Flagellum Unspun
The basic prediction the article makes (correct me if I am wrong) is that TTSS is homologous to the bacterial flagella, at the molecular level, and thus the flagella evolved from TTSS and itself is a "type of TTSS"(Mcnab).
Now this is nothing but the modified version of the EFM (Export-Filament-Motility) hypothesis, already once mentioned by Miller. The flaw(s) in this hypothesis is excellently summarised by Gene in his
response to Miller. He outlines a point that is very vital to be taken in consideration.
Is there any reason to think the type III export system, complete with the ancestors of flhA, flhB, fliR, fliQ, fliP, fliI and others, existed as a "cooptable part." Thus far, the answer is no, as there are good reasons to think the type III system evolved from pre-existing flagella.
The evidence for the above claim:
1. The bacterial flagellum is found in
both mesophilic and thermophilic bacteria, gram-positive and gram-negative, high GC and low GC content bacteria, and spirochetes. Type III systems seem to be restricted to a few gram-negative bacteria. That is, if we look at the sequenced genomes from the various groups cited above, we can find the genes for the bacterial flagellum but not the type III system genes.
2. Independent evidence suggests the type III system is recent. It is not only restricted to gram-negative bacteria, but to animal and plant pathogens. In fact, the function of the system depends on intimate contact with these multicellular organisms. This all indicates this system arose after plants and animals appeared.
In fact, the type III genes of plant pathogens are more similar to their own flagellar genes than the type III genes of animal pathogens. This has led some to propose that the type III system arose in plant pathogens and then spread to animal pathogens by horizontal transfer.
3. It's much easier to envision the evolution of the type III system from flagella than vice versa. For starters, evidence has surfaced that the basal body of the flagellum already works to secrete proteins other than the flagellar proteins, including virulence factors. Thus, the basal body is already poised to evolve into a type III system from the start. Evolution apparently would only have to duplicate and tweak the type III virulence protein secretion activity already existing in flagella. . In my opinion, this view is far more parsimonious than to propose that something like the type III system evolved long ago, was lost by all bacteria but gram-negative animal/plant pathogens and then was used to evolve the flagellum so that horizontal transfer could spread flagella far and wide (despite the lack of evidence for such transfer).
Thus, it should not be surprising that the scientific opinion has been converging on the notion that the export machinery evolved from the flagellar machinery. (5,7)
Is there any evidence that supports transporting this system, or something like it, back in time? The type III system is one of at least four different bacterial protein transport systems. And it appears to be the most complex of the bunch. The key here is that the type III/flagellar cytoplasmic export system does not show clear homology with any of these other transport systems. But we also know that evolution builds on and modifies what already exists rather than create de novo. Thus, if these other transport systems were already in place (and they probably were), why didn't evolution simply build on one of the simpler versions rather than create a whole new method of protein secretion de novo? The type III-from-flagellum scenario better fits with what we know about evolution - that it uses what already exists rather than inventing de novo. Thus, not only is there no evidence to support putting this transporter (or something closely homologous) back in pre-flagella days,
there is reason to think it wouldn't be there.
Another fundamental problem with the first step of the EFM hypothesis is that
it assumes IC to explain IC. Consider that the flagellum is composed of about 20 different proteins. Of those twenty, ten are homologous to the type III export machinery. Thus, this hypothesis begins its attempt to explain the origin of a 20-part IC system by assuming the existence of half of it (10 parts).
Let's briefly consider the 10 parts of the type III export machinery, where I'll use the flagellar gene names. There is FliI, an ATPase that is anchored to cytoplasmic face of the inner membrane. It may provide energy for the synthesis of the export machinery or transport of secreted proteins. It is thought to capture proteins in the cytoplasm for transfer to the secretory apparatus. There are several proteins that span the inner membrane and probably make up the protein conducting channel, including FlhA, FliP, FliQ, FliR, and FlhB. There is FliF, which in flagella, form the MS ring. And there is FliN and FliG, which in flagella, make up the C ring (located beneath the MS ring). Finally, there is FliH, with an unknown function.
Whether all 10 proteins are required for type III transport is unknown, but it appears most are essential:
quote:
Several proteins essential to secretion including LcrD, YscD, R, S, T, and U, are known or predicted to reside in the inner membrane (10,12,48-50). At the outer membrane, only one protein, YscC (48), and two lipoproteins, YscJ and VirG (51,52), appear essential for proper secretion. The roles and subcellular locations are not known for several more essential proteins, YscE, F, G, I, K, and L (9,48,51). How all of these proteins interact with one another to form the secretion apparatus is not yet understood. It is clear, however, that correct assembly of the apparatus is required not only for secretion, but also for normal synthesis of effector molecules (47,48). If one component of the export machinery is missing, production of the effector molecules is altered. [7]
There is yet another interesting aspect to all this. Since evolving from some flagellum, the type III transport system appears to have lost its ability to engage in rotary transport. The flagellar motor is composed of five proteins: MotA, MotB, FliG, FliN, and FliM. We'll discuss this more below, but right now it is worth pointing out that the type III systems have no homologs for MotA, MotB, or FliM. The Mot proteins are essential components of the motor, as they are membrane proteins that fulfill two functions: they transport ions to provide the energy for rotation and serve as the stator against which the rotor (FliG, FliN, FliM) moves. What's more, the type III rotor components have significantly changed. The type III homolog of FliN shares sequence similarity only with in its C-terminal 80 amino acids. And the sequence similarity between the FliG homologs are almost non-existent. Furthermore, there have been significant changes in FliF. FliF forms the MS ring (the "mounting plate"), which is associated with and above the C-ring composed of FliG, M, and N. FliF in flagella is composed of 500+ amino acids, but in the type III homolog, both the C- and N-terminal domains thought to be involved in forming the MS ring are missing. All that is left in common between them is a central region of about 90 amino acids.
Here we find another reason to recognize the significance of the flagellum-to-type III system evolution. Type III systems have apparently lost their ability to rotate. Thus, we can't think of type III systems as something pre-adapted to rotate, as all the rotary information has been lost. To argue that the type III system could reacquire the ability to rotate, as the flagellum does, is to essentially violate Dollo's Law, which states:
"evolutionary change manifested at any level higher than the genetic is irreversible, and that anatomical structures or functions once lost cannot be regained." [8] Yet by proposing that the flagellum once existed as a type III system and later acquired the ability to rotate is not hardly any different that proposing type III systems could reacquire the ability to rotate and violate Dollo's Law.
A Summary of the problems of Miller's hyothesis:
- There are good design reasons for building the flagellum around a transport system and attempts to assign historical significance to this are completely unsupported.
- We have the ability to imagine simpler initial states for designed systems where our imagination does not reflect reality. Thus, the mere ability to imagine simpler states is rather meaningless.
- The data suggest that not any transporter is good enough for evolving something like the bacterial flagellum. This is important because the EFM never addresses the origin of the transporter itself. It seems quite plausible that selection pressures for evolving a good transporter would steer the system away from being preadapted to form something like the flagellum (which is why bacterial flagella are monophyletic).
- There is no evidence that anything like the type III system predated the flagellum. The type III system itself most likely evolved from a flagellum.
- Because it is known that evolution borrows, rather than invents de novo, proposing the de novo evolution of a type III transport system among bacteria that already had several transport systems in place makes little sense.
- The type III system itself is IC, perhaps with ten IC components. No attempt is made to explain its flagella-independent origin.
- In light of the evolution of the type III system, proposing a type III-to-flagellum evolution appears to violate Dollo's Law.
Regards,
Ahmad
Footnotes:
(5)Nguyen L, Paulsen IT, Tchieu J, Hueck CJ, Saier MH Jr. 2000. Phylogenetic analyses of the constituents of Type III protein secretion systems. J Mol Microbiol Biotechnol Apr;2(2):125-44.
(7)
Molecular Mechanisms of Bacterial Virulence: Type III Secretion and Pathogenicity Islands
(8)
Dollo's Law
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