用于发现远距离蛋白质同源性的反向翻译
Back-translation for discovering distant protein homologies
摘要：
编码蛋白质的DNA序列中的移码突变在所产生的蛋白质序列中产生剧烈变化，这阻止了经典的蛋白质比对方法揭示蛋白质的共同起源。此外，当大量的取代另外涉及分歧时，即使在DNA水平上同源性检测也变得困难。为了应对这种情况，我们提出了一种新的方法来推断两种蛋白质的远距离同源关系，该方法考虑了可能影响编码序列的移码和点突变。我们设计了一个动态规划比对算法的内存效率的图形表示的一套完整的推定的DNA序列的每种蛋白质，确定两个推定的DNA序列具有最好的评分比对下一个强大的评分系统，旨在反映最可能的进化过程的目标。这使我们能够发现传统比对方法无法捕获的进化信息，这些信息已被生物学上重要的例子所证实。
英文摘要：
Frameshift mutations in protein-coding DNA sequences produce a drastic change in the resulting protein sequence, which prevents classic protein alignment methods from revealing the proteins' common origin. Moreover, when a large number of substitutions are additionally involved in the divergence, the homology detection becomes difficult even at the DNA level. To cope with this situation, we propose a novel method to infer distant homology relations of two proteins, that accounts for frameshift and point mutations that may have affected the coding sequences. We design a dynamic programming alignment algorithm over memory-efficient graph representations of the complete set of putative DNA sequences of each protein, with the goal of determining the two putative DNA sequences which have the best scoring alignment under a powerful scoring system designed to reflect the most probable evolutionary process. This allows us to uncover evolutionary information that is not captured by traditional alignment methods, which is confirmed by biologically significant examples.
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