Evolution of protein complexes

One of the recurring modes adopted by Intelligent Design creationists is to adopt the strategy whereby an example of a complex biological system is looked at and it is decided that evolution cannot explain its origin. We see this enshrined in bogus concepts such as ‘irreducible complexity’, ‘specified functional information’ and the like. By claiming a process of inference, ID creationists seek to declare that an intelligent designer must have been involved in the appearance of such complex systems.

Of course, the problem with this strategy is that one by one, these examples are likely to fall to genuine scientific advance (examples include Behe’s favourites such as the bacterial flagellum and the vertebrate immune system spring to mind).  A neat example of  an approach to better understanding the evolution of protein complexes has just appeared as an Advance Online Publication at Nature (Finnigan et al (2012) Nature “Evolution of increased complexity in a molecular machine” doi:10.1038/nature10724). There’s also an accompanying News and Views article (Doolittle (2012) Nature “Evolutionary biology: A ratchet for protein complexity” doi:10.1038/nature10816).

Schematic diagram of V-ATPase

Schematic diagram of V-ATPase

V-ATPases are membrane bound protein complexes that serve to translocate protons across membranes, and important cellular function that maintain the pH within membrane bound organelles.  The diagram shows a representation of the V-ATPase.  The pink ring of subunits is the Vo subcomplex, a membrane bound assembly of six proteins, each with several membrane spanning domains.  In the majority of eukaryotes, there are two distinct related proteins in the Vo-ATPase subcomplex, while in fungi there are three, known as Vma3, Vma11 and Vma16.  The different subunits do not randomly associate: of the six proteins in the yeast Vo-ATPase, for example, there are four molecules of Vma3 and one each of Vma11 and Vma16. Vma11 always lies between Vma3 and Vma16, and and Vma3 cannot interact with the same surface of Vma16 that Vma11 can.

An attractive proposal for the evolutionary origin of the three Vo-ATPase subunits would be via a process of gene duplication and subsequent divergence of the resulting paralogues. In the case of the fungi, at least two such gene duplication events would be inferred to give rise  to the three Vo-ATPase subunit proteins.  Finnigan et al took a very interesting approach to looking at the evolution of the yeast (budding yeast, Saccharomyces cerevisiae) Vo-ATPase proteins in which a bioinformatic approach to inferring the sequence of last common ancestors was married to a more conventional approach of expressing protein sequences in yeast of a variety of genotypes.  Yeast is particularly well-suited to these sorts of analyses, as targetted mutagenesis of specific genes is very simple and rapid, and the technology of gene expression is well developed.

A candidate ancestral protein to Vma3 and Vma11 (referred to as Anc.3-11) was predicted from the bioinformatic analysis, a corresponding gene synthesised in vitro and expressed in yeast, and its ability to complement deletion mutants of Vma3 and Vma11 assessed by testing viability of the complemented yeast mutant to grow on a selective medium.  Further experiments used gene fusions to evaluate the ability of proteins to interact with different sides of the V-ATPase subunits. Anc.3-11 protein successfully complements mutations in Vma3 and Vma11.  The proposed scheme is that gene duplication gave rise to two paralogues.  These paralogues ultimately gave rise to Vma3 and Vma11, Vma3 losing the ability to interacte with the  ‘anticlockwise’ side of Vma16 and Vma11 losing the ability to interact with the ‘clockwise’ face of Vma16 and probably one face of Vma3.

The authors went on to investigate specific sequence changes which arose during the evolution of the Vo-ATPase subunits with the intention of narrowing down the individual amino acid changes that are responsible for the interaction changes.  Single amino acid changes were identified which altered the interaction behaviour of Anc.3-11 such that it lost the ability to behave as both Vma3 and Vma11 but instead acquired the binding properties of Vma3 or Vma11. The paper concludes by noting that

This view of the evolution of molecular machines is related to recent models that explain other biological phenomena—such as the retention of large numbers of duplicate genes and mobile genetic elements within genomes—as the product of degenerative processes acting on modular biological systems. Although mutations that enhanced the functions of individual ring components may have occurred during evolution, our data indicate that simple degenerative mutations are sufficient to explain the historical increase in complexity of a crucial molecular machine. There is no need to invoke the acquisition of ‘novel’ functions caused by low-probability mutational combinations.

Apart from observing that this paper presents a really neat approach to investigating evolutionary origins of protein complexes, it seems to me that the findings make a serious inroad into the understanding of how mutations that may be neutral or ‘degenerative’ can bring about the increase in complexity of a multiprotein subunit.  And from the perspective of Science versus Intelligent Design creationism, it clearly illustrates the gulf between Intelligent Design creationism (where one throws up one’s hands and capitulates to state of ignorance and then to the acceptance of a supernatural entity) and a truly scientific approach in which a sensible investigative approach is undertaken to solve a biological problem. Furthermore, I think the findings in this paper are relevant to asking whether concepts such as ‘irreducible complexity’ have any validity.

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