Joined: May 2002
Following the tangent of the evolution of repeats *within* protein sequences:
Protein Repeats: Structures, Functions, and Evolution
pp. 117-131 (doi:10.1006/jsbi.2001.4392)
Miguel A. Andrade*, , Carolina Perez-Iratxeta*, , Chris P. Ponting
Internal repetition within proteins has been a successful strategem on multiple separate occasions throughout evolution. Such protein repeats possess regular secondary structures and form multirepeat assemblies in three dimensions of diverse sizes and functions. In general, however, internal repetition affords a protein enhanced evolutionary prospects due to an enlargement of its available binding surface area. Constraints on sequence conservation appear to be relatively lax, due to binding functions ensuing from multiple, rather than, single repeats. Considerable sequence divergence as well as the short lengths of sequence repeats mean that repeat detection can be a particularly arduous task. We also consider the conundrum of how multiple repeats, which show strong structural and functional interdependencies, ever evolved from a single repeat ancestor. In this review, we illustrate each of these points by referring to six prolific repeat types (repeats in -propellers and -trefoils and tetratricopeptide, ankyrin, armadillo/HEAT, and leucine-rich repeats) and in other less-prolific but nonetheless interesting repeats.
[...see especially the ribbon models in this paper]
Our survey of protein repeats has highlighted the multifunctionality of repeat types, their structural
differences, and their proliferations in different evo-lutionary
lineages. One likely reason for their evo-lutionary success is that repeat-containing proteins are relatively “cheap” to evolve. By this we mean that large and thermodynamically stable proteins may arise by the simple expedient of intragenic du-plications, rather than the more complex processes of de novo a-helix and b-sheet creation. This is sup-ported by the larger sizes of most repeat-containing
structures relative to compact domains (Fig. 4).
This does not, of course, present a complete an-swer
to their success since it addresses the question of how repeat-containing proteins arose, rather than why they have been selected for and fixed in evolu-tionary lineages on so many separate occasions. As suggested throughout this review, the reasons for the functional successes of repeat classes may be a proclivity of repeat assemblies to acquire different molecular functions, namely, the association with
different protein ligands. This, in turn, might be associated with the large solvent-accessible surface areas, presented by extended “open” assemblies, that are available for interactions with ligands. This is because burial of nonpolar residues at protein–protein interfaces is thought to be an important contributor to heterodimer stability (Tsai et al.,
In understanding the evolution of repeats, one major problem remains. Repeats are defined as oc-curring multiply, and all repeats in a family are homologous. This means that these repeats all evolved from a common ancestor, which necessarily must have contained only a single repeat. This is
apparently contradictory, since it is not expected that a single repeat could exist in isolation, as a single folded functional unit. Rescue is at hand if one suggests that the family’s common ancestor indeed represented a single repeat, but one that formed homooligomers. The homooligomeric structure of the ancestor might mirror that of the intrachain repet-itive structure of its modern homologue, except in its multichain character. This scenario has recently been suggested for the evolution of the b-trefoil fold (Ponting and Russell, 2000).
A problem with this proposal is that there are few, if any, known examples where homologous multire-peat assemblies are formed both from oligomers of single repeats and from a single chain of multiple repeats. However, this might not be too surprising since the highly cooperative process of folding a mul-tirepeat protein must be significantly more favor-able
than folding a homooligomeric protein from its constituent monomers. This is because the kinetic folding pathways of multirepeat protein structures may be nucleated at many positions. In this way ancient oligomeric single repeat proteins might have been driven to extinction by their monomeric multi-ple repeat-containing homologues.
There is an interesting analogy here to the "serial homology" concept in traditional organismal evolution -- e.g. the duplication and specialization of segments. The same idea -- duplication and divergeence -- appears to occur on several different molecular levels, to wit:
- duplication of segments of a protein, followed by rapid divergence (the above paper)
- taking a homodimer, homotrimer, etc., duplicating the gene, and then specializing each gene in the e.g. heterodimer. This is yet another way to produce IC by the way
- traditional gene duplication
- duplication of whole chromosomes/genomes -- many chunks will decay but some may get new functions.
All this could be treated in much more detail. However, antievolutionists consistently fail to realize the importance of duplication, and write as if it didn't exist. E.g., John Bracht's recent post to metanexus:
Knotty Pine and Corroding Coins: John Bracht
For concreteness, consider an example. Think of a man-made outboard motor. This system contains many of the same structures found in the bacterial flagellum: a motor (including stator, rotor, and acid-powered drive), drive shaft, u-joint, and propeller. Now, imagine starting with a basic rowboat and trying to evolve an outboard motor via the co-optation model. Perhaps, somehow, the metal outer skin of the boat peels up in the back and this forms a useful rack for a fishing pole, and is available to provide the internal support and external protective casing for the motor. Perhaps a support rod works loose from the hull and is available to be made into a drive shaft. But how do we move on from here to build up the motor, in functional steps, from existing parts? The problem is this: the various parts are already adapted to their old functions. To build an outboard motor, the old functions must be replaced by new functions. New functions require modifications of the old parts, and since the motor system doesn't work until all the parts are assembled, we inevitably need a large amount of coordinated change in various components before we can build the new system. For instance, the peeled-away metal on the back (previously adapted to form a watertight hull) will have to undergo extensive modification, including careful bending or shaping, and drilling holes in appropriate places to support motor components (all without letting the hull become leaky). The support rod from the hull, destined to become the drive shaft, will also need modification for attaching gears and the universal joint (and the removal of the support rod must not weaken the structural integrity of the boat). And so on.
IMO there is a clear assumption here that we are dealing with *one* copy of everything, that the old function is lost as the new function is gained. But just ain't so...