Tuesday, March 11, 2014

Follow up: Mutation


    In the previous post, I have tried to argue over the fact as to why we wouldn't ever have a system where there is zero mutation. Ability to mutate, provides a competitive edge. I also highlighted on why mutation is favoured despite a heavy loss in terms of population number, as the case seems to be in the first place. But somebody had this question. Why didn't in that case life evolve a very high mutation rate?
Fig 1: Comparison of mutation rates.

    Intuition says if we had a very high mutation rate, such that every new generation has a new variant wouldn't it provide a gambling advantage. The answer, though temptingly “Yes” is a “NO”. As in my previous post to argue on the reason you have to set-up another thought experiment.

      Set up a culture condition, with a strain X, which has such a high mutation rate that every new progeny is a variant. Round one of replication, 2 new strains are generated with new mutations. As I said in my previous post, most of the mutations are deleterious (When I say most, I mean to say that almost 50-80% of the mutation is not compatible). Probability says that there is more chance that both the cells will not survive. And gene pool is not saved. Clearly a bad strategy. Even if the low probability event of a single strain acquiring the good mutation (or at least a life compatible mutation), the very next round of replication, it would be lost. My point is simple, there is no back up copy of the original version which can be relied upon.

    This is the basis of mutation. You need to strike a balance between how much you can mutate and how much you cannot. It is important not to lose a backup copy of the original genotype. This ensures that the newly created versions (which are far less in number than the original type) need to be better and thus compete with the original type to establish itself. This ensures evolving strains are better in a given set of condition.

      It is important to understand that mutation is not a universal improvement in the organism. Mutation confers the ability to survive and reproduce in a given condition only. There is a trade off (I borrowed this from R Dawkins argument; From the book titled “Greatest Show on Earth”). A bacteria that is more antibiotic resistant (by virtue of sat multiple plasmids), would have traded off some genes that are related to virulence. In other words, the strain is extremely fit to deal with strong antibiotics but less virulent. This phenomenon has been published by multiple studies. If the heavy pressure of antibiotics is lifted off, the organism may regain some virulence and lose some of the resistance plasmids. You see, it is very costly to maintain additional genes, for no reason. This is exactly the reason, why strategies such as not using certain type of antibiotics, for a sufficient period of time, gives rise to sensitive mutants or revertants.

Schulz zur Wiesch P, Engelst├Ądter J, & Bonhoeffer S (2010). Compensation of fitness costs and reversibility of antibiotic resistance mutations. Antimicrobial agents and chemotherapy, 54 (5), 2085-95 PMID: 20176903

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