Saturday, 16 May 2009

How do enzyme mechanisms evolve?

Evolution is a fascinating topic. Although the principal mechanism by which evolution occurs is quite simple to understand, namely the introduction of changes (mutations) into the DNA, the consequences that follow are enormous.

The term selective pressure is used to describe an imaginary operator that affects the incidence of particular mutations in a population. What makes evolution difficult for me to get my head around is that selection operates on many levels. In a population, a particular physical characteristic might be more advantageous (think of the famous finches) or more attractive. In your DNA, a particular mutation might preserve the amino acid coded for, or it may change to another amino acid that does not affect the protein's function. On the other hand, if the amino acid is involved in the catalytic action of the protein it's going to be conserved, right? But then how do new mechanisms evolve?

My former postdoc supervisor, Dr. John Mitchell, is currently advertising a PhD position on "Modelling the Evolution of Enzyme Catalysis" at the University of St. Andrews. I'm particularly interested in this project as it builds on earlier work I carried out in the Mitchell Group along with Gemma Holliday and Daniel Almonacid. Here's an excerpt from the project description:
We will create a simulation using a population of model enzyme-catalysed reactions, mimicking a state early in evolutionary history, and allow them to evolve in EC space. The reactions will consist of steps and be represented, in a manner familiar from genetic algorithms, by "chromosomes" describing the chemical properties of each step. Parameters will control the likelihood of different kinds of evolutionary event, such as a change of substrate with the same underlying chemical mechanism, taking place. The simulations will be calibrated, and then compared with the results from a study of real-world convergent and divergent evolution.
Cool. Closing date 31 July.

Image credit: Colin Purrington

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