Darwinian evolution in a primitive cell

Hi all. I feel totally ashamed because of my poor blog performance. I simply could not find a single hour to write a short review of papers that I have recently read or skimmed through.

This time I would like to discuss a recent paper of Professor Tetsuya Yomo from Osaka University. In this paper authors have established a platform for artificial evolution of systems containing of multiple components. As an object for selection they have chosen RNA directed RNA polymerase of Qbeta phage (Qbeta polymerase). This protein is known as the most productive RNA-polymerase and according to previous reports can produce up to 10¹⁰ copies of a single RNA template in 10 min. However, there are a major problems with this enzyme: (1) it's incredibly specific and can amplify only phage RNAs; and (2) it is often contaminated with phage RNA-derived small parasitic RNAs that effectively outcompete replication of genomic RNA. Thus whoever can 'teach' this protein to replicate RNA molecules of our interest that also will be resistible to the presence of parasitic RNAs can build (to say the least) very efficient way to amplify RNA molecules. 

What's more important you can design an artificial cell that will be contained of many components who's RNA templates will be replicated by Qbeta polymerase. Further application will be really dependent on you imagination. Firstly, you can explore the very basic principles of evolution of complex per-biological systems. Thinking of more practical and immediate use: one can design a self-sustained cell-free translation system, that will only be consisted of proteins and RNAs that you need and properties you dare to want. 

Alternatively, even without approaching such a tantalizing goal, you can perform an artificial evolution experiments of the systems of proteins. This was not possible so far and the protein engineering exercises have been done only for single relatively 'simple' protein species.

So what group of Professor Tetsuya Yomo have done? They simply overcome the problem of presence of parasitic RNAs by compartmentalizing the replication reaction in lipid vesicles. Such that non-functional RNAs that were prevailing in the replication mix were to a major extent eliminated during evolution iterations. Also, in order to be able to keep the mutant RNAs and Qbeta replicase isolated from the others mutants they fused the RNA replication vesicles with vesicles that contained E.coli translation extract (so called PURE system).

This compartmentalization approach reminded me a story of one of the prisoner's dilemma variants that was explained in 'Supercooperators' book, when 'defectors' that use resources of others without giving back normally outcompete 'cooperators' in a homogeneous environment but as soon as group of interacting 'units' become isolated - cooperators thrive. This, for instance, was a good way to show the importance of a group selection in evolution.

Although the authors have not reached the ultimate goal to have omni-reactive Qbeta polymerase (in fact they have not even mentioned this in the paper) they were able to get mutant polymerase that was efficiently replicating its RNA long template (mutant again) even in the presence of parasitic RNAs. That means, that authors, are well on the way to design a replicase that will be able amplify RNAs containing genes of our, or in fact, their interest.

Interestingly, that evolution of such primitive cell (as they call it) which is not alive demonstrated traits of Darwinian (i.e. biological) evolution. These are 'diminishing returns' (where the smaller benefits can be gained per mutation upon reaching the optimum) and more importantly 'rate of mutations' happened to be constant throughout all evolutionary experiment. The same have recently been shown for E.coli cells (living matter!). I wonder if this rate is close to the optimum of viruses or relatively simple bacterias.