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

论文研究：随机突变的协同上位性：实验和理论方法

• 批准号: 9801639
• 负责人: James Bull
• 金额: $ 0.7万
• 依托单位: University of Texas at Austin
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-06-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9801639&HistoricalAwards=false
• 关键词: Dissertation; Research; Synergistic; Epistasis; Random

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.

公牛9801639 突变总是在生物体的基因组中积累。这些大多数不利的影响只能通过选择，即通过携带突变的个体的死亡或不育来消除。因此，一个种群的遗传健康部分取决于自然选择的作用有多强。 如果一个生物体的遗传学具有某种特性，选择就可以更有效地清除有害的突变。这项研究试图了解一个非常简单的生物体的基因是否表现出这种称为协同上位性的特性。上位性是指突变之间存在相互作用。在这种情况下，两个突变一起的影响不同于仅仅将每个突变本身的影响相加所预期的影响。协同上位性是指两个突变的效果比每个突变的单独效果之和更差的情况。(The相反的效应，其中两个突变的危害小于其个体效应的总和，被称为拮抗或递减回报上位性）。 协同上位性已被假定为遗传系统的一般性质。它被认为是导致有性生殖进化的一种可能的驱动力，并对自然选择的效率有广泛的影响。 这项研究将研究一种非常简单的生物体--噬菌体PhiX 174，看看突变是否具有协同作用。使用这样一个简单的模型系统的优点在于，否则很难确切地知道哪些突变存在，以及它们如何相互作用。拟议的系统将避免这一点和其他问题所面临的先前的研究，寻找证据的协同作用。