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

公牛9801639的突变总是在生物体的基因组中积累。这些最不利的影响只能通过选择来消除，也就是通过携带突变的个体的死亡或不育来消除。因此，一个群体的遗传健康在一定程度上取决于自然选择的作用有多强。如果生物体的基因具有某种特性，那么选择就能更有效地剔除有害突变。这项研究试图了解一个非常简单的有机体的基因是否表现出这种被称为协同上位性的特性。上位性是指突变之间存在交互作用。在这种情况下，两个突变一起的影响与仅仅将每个突变的影响加在一起的预期是不同的。协同上位性是指两个突变的影响比每个突变单独影响的总和更差的情况。(相反的效应，即两个突变的危害小于它们各自影响的总和，称为对抗性或递减回报上位性)。协同上位性一直被认为是遗传系统的一种普遍属性。它被认为是导致有性繁殖进化的可能驱动力，并对自然选择的效率具有广泛的影响。这项研究将着眼于一个非常简单的有机体--噬菌体phiX174，看看突变是否具有协同作用。使用如此简单的模型系统的优势在于，否则很难确切知道存在哪些突变，以及它们是如何相互作用的。拟议的系统将避免这一问题以及之前寻找协同效应证据的研究所面临的其他问题。

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.