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首页> 外文会议>Pacific Symposium on Biocomputing 2002, Jan 3-7, 2002, Kauai, Hawaii >EVIDENCE FOR SEQUENCE-INDEPENDENT EVOLUTIONARY TRACES IN GENOMICS DATA
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EVIDENCE FOR SEQUENCE-INDEPENDENT EVOLUTIONARY TRACES IN GENOMICS DATA

机译：基因组数据中与序列无关的进化轨迹的证据

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摘要

Sequence conservation during evolution is the foundation for the functional classification of the ennormous number of new protein sequences being discovered in the current era of genome sequencing. Conventional methods to detect homologous proteins are not always able to distinguish between true homologs and false positive hits in the twilight zone of sequence similarity. Several different approaches have been proposed to improve the sensitivity of these methods. Among the most successful are sequence profiles, multi-linked alignment, and threading. However, evolution might offer up other clues about a protein's ancestry that are sequence independent. Here we report the discovery of two such traces of evolution that could potentially be used to help infer the fold of a protein and hence improve the ability to predict the biochemical function. The first such evolutionary trace is a conservation of fold along the genome, i.e. nearby genes tend to share a fold more often than expected by chance alone―a not unexpected observation, but one which holds true even when no pair of genes being examined share appreciable homology. The second such evolutionary trace is, surprisingly, present in expression data: genes that are correlated in expression are more apt to share a fold than two randomly chosen genes. This result is surprising because correlations in expression have previously only been considered useful for determining biological function (e.g. what pathway a particular gene fits into), yet the observed fold enrichment in the expression data permits us to say something about biochemical function since fold corresponds strongly with biochemical function. Again, the fold enrichment observed in the expression data is apparent even when no pair of genes being examined share appreciable homology.
机译：进化过程中的序列保守性是目前基因组测序时代发现的大量新蛋白序列进行功能分类的基础。检测同源蛋白的常规方法并不总是能够在序列相似性的暮光区中区分真正的同源物和假阳性。已经提出了几种不同的方法来提高这些方法的灵敏度。其中最成功的是序列配置文件，多链接比对和穿线。但是，进化可能会提供与蛋白质祖先无关的其他线索，这些线索与序列无关。在这里，我们报告发现了两条这样的进化痕迹，这些痕迹可潜在地用于帮助推断蛋白质的折叠，从而提高预测生化功能的能力。第一个这样的进化轨迹是沿基因组的折叠保守性，即附近的基因往往比偶然偶然地所期望的共享更多倍的折叠-这并非意料之外的观察，但是即使当没有被检查的一对基因共享可观时，这一事实仍然成立同源性。出乎意料的是，表达数据中出现了第二条这样的进化轨迹：与两个随机选择的基因相比，表达相关的基因更容易共享一个折叠。这个结果令人惊讶，因为表达相关性以前仅被认为可用于确定生物学功能（例如特定基因适合的途径），但是在表达数据中观察到的倍数富集使我们可以对生化功能说些什么，因为倍数强烈对应具有生化功能。再次，即使没有被检查的基因对具有明显的同源性，在表达数据中观察到的倍数富集是明显的。

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