Dissertation Research: Synergistic Epistasis of Random Mutations: Experimental and Theoretical Approaches

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Bull 9801639 Mutations are always accumulating in an organism's genome. These mostly disadvantageous effects can only be removed by selection, that is, by the death or sterility of the individuals carrying the mutations. The genetic health of a population therefore depends in part upon how strongly natural selection is acting. If the genetics of an organism has a certain property, selection can become much more efficient at weeding out deleterious mutations. This study is attempting to see whether or not the genes of a very simple organism show this property, called synergistic epistasis. The term epistasis refers to the presence of an interactive effect between mutations. In this case, the effect of two mutations together is different than would be expected from merely adding the effects of each mutation by itself. Synergistic epistasis refers to the condition where the effect of two mutations is worse than the sum of the individual effects of each. (The opposite effect, where two mutations are less detrimental than the sum of their individual effects, is called antagonistic or diminishing returns epistasis). Synergistic epistasis has been postulated as a general property of genetic systems. It has been implicated as a possible driving force leading to the evolution of sexual reproduction, and has broad implications for the efficiency of natural selection. This study will look at a very simple organism, the bacteriophage PhiX174, to see if mutations behave synergistically or not. The advantages of using such a simple model system revolve around the fact that it is otherwise very difficult to know exactly which mutations are present, and how they interact. The proposed system will avoid this and other problems faced by previous studies that have looked for evidence of synergism.