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

9629440史密斯病毒分子进化：适应性、竞争和重组在RNA病毒对动物的自然感染中，病毒由具有相关但不相同遗传物质分布的病毒“群”组成。这些病毒产生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，它包含其遗传物质的两个副本，在将RNA基因组复制到DNA的过程中，高重组率使其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；增加新突变融入种群的比率；并通过允许新的突变组合来增加可变性。这项提议的目标是精确测量病毒生长的几个方面；利用这些结果来预测突变体在存在或不存在新环境时相互竞争的能力（特定化学选择）；并在这些突变位点检测病毒基因组之间的重组。这一组的一个成员HIV-1，作为研究RNA病毒分子进化的模型系统具有独特的资格：它可以作为克隆获得，其整个核苷酸序列已被确定，并且已知具有化学抗性的突变体，其确切突变已被确定。这使得突变体和它的等基因野生型菌株可以进行比较，除了有问题的突变外，它们的序列完全相同。同样，在存在或不存在特定选择的情况下，完全等基因菌株的竞争也可以进行。这种病毒在自然界中的进化速度大约比高等生物基因的估计速度高10万到100万倍。此外，该病毒在自然界的半衰期约为2天，因此可以在相对较短的时间内研究大量的代。因此，该模型系统提供了一个独特的机会来研究种群生物学中迄今为止已经在理论上建模的问题，或者由于长时间生成而难以获得足够数据的问题。

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.