Statistical Models for Detecting Gene Conversion

索耶9707045 研究者开发用于检测基因转换的统计检验。 基因转换是生物学中导致一段DNA复制到另一段DNA的任何过程。 基因转换是进化过程中的一个重要过程，也对人类健康产生影响。 例如，它可以导致细菌之间的致病特性和病毒之间的病毒基因组的部分转移。 研究并扩展了用于检测对齐的DNA或氨基酸序列中的基因转换的统计检验。 特别强调的是置换或置换类的测试，可以评估异常长的片段上的两个序列是相似的，否则一个单一的序列是异常的分歧。(This包括Karlin-Altschul类型的测试，其执行速度更快，但不如置换测试准确。该提案的一些具体目标是：（i）通过寻找相似性分数而不是片段长度的高分片段来扩展这些测试以允许偶尔的错配和比对缺口，（ii）开发提高这些测试的能力和有效性的方法，（iii）比较用于检测基因转化的统计程序的效率和能力，以及（iv）在网站上向生物界提供由此产生的改进软件。 人类艾滋病毒和流感病毒属于一个病毒家族（RNA逆转录病毒），不仅具有高度可变性，而且还可以在它们之间交换遗传物质。 能够交换遗传物质块的病毒更危险，因为病毒中更具适应性的部分可以迅速传播，而且因为仅针对病毒部分的疫苗可能会迅速过时。 在这个病毒家族中还有几个植物病毒家族，它们对具有经济重要性的粮食作物造成损害。 该项目扩展了一种统计测试，可以从遗传序列的样本中检测出这种交换的历史，并将统计可能性的度量分配给最可能的事件。 这将有助于理解这些特定病毒进化的本质。 这项工作扩展了研究人员早期的工作，即在假设交换的材料没有发生后来的突变的情况下，在比对的DNA序列中寻找可能的交换事件。 这种假设不适用于这些高度可变的病毒。 此外，最近的研究表明，早期的测试在某些程序中存在偏差，可能会隐藏一些交换（或基因转换）事件的证据。 这种偏见被消除了。 最后，生物界可以在互联网上更多地获得执行改进程序的计算机软件，包括列出最有可能的交换事件及其统计可能性。（实现早期程序的软件已被广泛使用。

Sawyer 9707045 The investigator develops statistical tests for detecting gene conversion. Gene conversion is any process in biology that causes a segment of DNA to be copied to another DNA segment. Gene conversion is an important process in evolution, and also has consequences for human health. For example, it can cause the transference of pathogenic traits between bacteria and parts of viral genomes between viruses. Statistical tests for detecting gene conversion in aligned DNA or amino acid sequences are studied and extended. Particular emphasis is given to permutation or permutation-like tests that can evaluate unusually long segments on which two sequences are similar, or else on which a single sequence is unusually divergent. (This includes tests of Karlin-Altschul type, which are faster to perform but are not as accurate as permutation tests.) Some specific aims of the proposal are: (i) to extend these tests to allow occasional mismatches and alignment gaps by finding high-scoring segments for a similarity score rather than segment length, (ii) develop ways to improve the power and effectiveness of these tests, (iii) compare statistical procedures for detecting gene conversion in regards to efficiency and power, and (iv) make the resulting improved software available to the biological community on a Web site. Human HIV and influenza viruses belong to a family of viruses (RNA retroviruses) that not only are highly changeable, but can also exchange pieces of genetic material among themselves. Viruses that can exchange blocks of genetic material are more dangerous since the more adaptive parts of the virus can spread rapidly, and since vaccines that target only part of the virus can become rapidly obsolete. There are also several families of plant viruses in this viral family that cause damage to food crops of economic importance. The project extends a statistical test that can detect a history of such exchanges from a sample of genetic sequ ences and assign measures of statistical likelihood to the most likely events. This will help to understand the nature of the evolution of these particular viruses. The work extends earlier work of the investigator that looked for possible exchange events in aligned DNA sequences under the assumption that the exchanged material had not undergone later mutation. This assumption does not hold for these highly mutable viruses. In addition, recent work has shown that the earlier test has biases in some of its procedures that can hide evidence for some exchange (or gene conversion) events. This bias is removed. Finally, computer software that implements the improved procedures, including listing the most likely exchange events and their statistical likelihood, is made more available on the internet for the biological community. (Software that implements the earlier procedures has been widely used.)