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

9629440史密斯病毒分子进化：适合度、竞争和重组在由核糖核酸病毒自然感染的动物中，病毒由一群病毒组成，这些病毒具有相关但不相同的遗传物质的分布。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复制错误。在逆转录病毒的特殊情况下，它包含两份遗传物质，在将RNA基因组复制到DNA过程中的高重组率使其具有一些被认为对有性繁殖生物体重要的优势：消除对遗传物质的破坏；提高新突变纳入种群的速度；并通过允许新的突变组合来增加变异性。这项建议的目标是精确地测量病毒生长的几个方面；使用这些结果来预测突变株在新环境存在或不存在时相互竞争的能力(特定的化学选择)；并检查病毒基因组在这些突变位点的重组。HIV-1是这一组的成员之一，作为研究RNA病毒分子进化的模型系统，它具有独特的资格：它可以作为克隆获得，其整个核苷酸序列已经被确定，并且已经确定确切突变的化学耐药突变体是已知的。这使得可以比较突变株和其同基因野生型菌株，除了有问题的突变外，它们具有完全相同的序列。同样，在存在或不存在特定选择的情况下，可以进行完全相同基因的菌株的竞争。这种病毒在自然界中的进化速度大约是高等生物基因估计的10万到100万倍。此外，这种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世代。因此，这个模型系统为研究种群生物学中的问题提供了一个独特的机会，这些问题到目前为止都是从理论上建模的，或者由于世代时间长而很难获得足够的数据。

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.