CAA: RNA Virus Molecular Evolution: Fitness, Competition, and Recombination

CAA：RNA 病毒分子进化：适应、竞争和重组

• 批准号: 9629440
• 负责人: Marilyn Smith
• 金额: $ 5.5万
• 依托单位: University of Kansas Medical Center
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-15 至 1999-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9629440&HistoricalAwards=false
• 关键词: CAA; RNA; Virus; Molecular; Evolution

9629440 Smith Virus Molecular Evolution: Fitness, Competition, and Recombination In a natural infection of an animal by an RNA virus, the virus consists of a 'swarm' of virus with a distribution of related, but not identical genetic material. A major cause of diversity in these viruses is that the mechanism for copying their genetic material is prone to copying errors. In the special case of retroviruses, which contain two copies of their genetic material, a high rate of recombination during the copying of the RNA genome into DNA allows it to have some advantages proposed to be important for sexually reproducing organisms: removing damage to the genetic material; increasing the rate of incorporation of new mutation into the population; and increasing variability by allowing new combinations of mutations. The goal of this proposal is to measure precisely several aspects of virus growth; to use these results to predict the ability of mutants to compete with each other in the presence or absence of a novel environment (specific chemical selection); and to examine recombination between viral genomes at these mutation sites. A member of this group, HIV-1, possesses unique qualifications as a model system to study the molecular evolution of a RNA virus: it is available as a clone for which the entire nucleotide sequence has been determined, and chemically-resistant mutants are known for which the exact mutation has been identified. This allows the mutant and its isogenic wild-type strain, with exactly the same sequence except for the mutation in question, to be compared. Likewise, competition of completely isogenic strains in the presence or absence of specific selection can be carried out. The rate of evolution of this virus in nature is approximately 100,000 to one million time higher than that estimated for genes of higher organisms. In addition, the half-life of this virus in nature is on the order of 2 days, such that large numbers of generations may be studied in a rela tively short time. This model system therefore provides a unique opportunity to study questions in population biology that heretofore have been modeled theoretically, or in which sufficient data are difficult to obtain due to long generation times.

小行星9629440 病毒分子进化：适应性、竞争与进化 在RNA病毒对动物的自然感染中，病毒由一群分布相关但不相同的遗传物质的病毒组成。 这些病毒多样性的一个主要原因是复制其遗传物质的机制容易出现复制错误。 在逆转录病毒的特殊情况下，它含有两个拷贝的遗传物质，在RNA基因组复制成DNA的过程中，重组率很高，这使得它具有一些被认为对有性繁殖生物体很重要的优势：消除对遗传物质的损害;增加新突变进入种群的速度;通过允许新的突变组合来增加变异性。 该提案的目标是精确测量病毒生长的几个方面;使用这些结果来预测突变体在存在或不存在新环境（特定化学选择）的情况下相互竞争的能力;并检查这些突变位点处病毒基因组之间的重组。 HIV-1是这一组中的一员，它具有独特的资格作为研究RNA病毒分子进化的模型系统：它可以作为克隆获得，其整个核苷酸序列已经确定，并且已知具有化学抗性的突变体，其确切的突变已经确定。 这允许突变体和其同基因野生型菌株进行比较，除了所讨论的突变之外，它们具有完全相同的序列。 同样地，可以在存在或不存在特异性选择的情况下进行完全同基因菌株的竞争。 这种病毒在自然界中的进化速度比高等生物基因的估计速度高出大约10万到100万倍。 此外，该病毒在自然界中的半衰期约为2天，因此可以在相对较短的时间内研究大量的世代。 因此，该模型系统提供了一个独特的机会，研究人口生物学的问题，迄今为止已经建模理论，或在其中足够的数据是难以获得由于长的世代时间。