Cantarel Brandi L, Morrison Hilary G, Pearson William
Department of Biochemistry and Molecular Genetics, University of Virginia, VA, USA.
Mol Biol Evol. 2006 Nov;23(11):2090-100. doi: 10.1093/molbev/msl080. Epub 2006 Aug 4.
We have characterized the relationship between accurate phylogenetic reconstruction and sequence similarity, testing whether high levels of sequence similarity can consistently produce accurate evolutionary trees. We generated protein families with known phylogenies using a modified version of the PAML/EVOLVER program that produces insertions and deletions as well as substitutions. Protein families were evolved over a range of 100-400 point accepted mutations; at these distances 63% of the families shared significant sequence similarity. Protein families were evolved using balanced and unbalanced trees, with ancient or recent radiations. In families sharing statistically significant similarity, about 60% of multiple sequence alignments were 95% identical to true alignments. To compare recovered topologies with true topologies, we used a score that reflects the fraction of clades that were correctly clustered. As expected, the accuracy of the phylogenies was greatest in the least divergent families. About 88% of phylogenies clustered over 80% of clades in families that shared significant sequence similarity, using Bayesian, parsimony, distance, and maximum likelihood methods. However, for protein families with short ancient branches (ancient radiation), only 30% of the most divergent (but statistically significant) families produced accurate phylogenies, and only about 70% of the second most highly conserved families, with median expectation values better than 10(-60), produced accurate trees. These values represent upper bounds on expected tree accuracy for sequences with a simple divergence history; proteins from 700 Giardia families, with a similar range of sequence similarities but considerably more gaps, produced much less accurate trees. For our simulated insertions and deletions, correct multiple sequence alignments did not perform much better than those produced by T-COFFEE, and including sequences with expressed sequence tag-like sequencing errors did not significantly decrease phylogenetic accuracy. In general, although less-divergent sequence families produce more accurate trees, the likelihood of estimating an accurate tree is most dependent on whether radiation in the family was ancient or recent. Accuracy can be improved by combining genes from the same organism when creating species trees or by selecting protein families with the best bootstrap values in comprehensive studies.
我们已经描述了准确的系统发育重建与序列相似性之间的关系，测试了高水平的序列相似性是否能始终产生准确的进化树。我们使用PAML/EVOLVER程序的修改版本生成了具有已知系统发育的蛋白质家族，该程序会产生插入、缺失以及替换。蛋白质家族在100 - 400个点接受突变的范围内进化；在这些距离下，63%的家族具有显著的序列相似性。蛋白质家族使用平衡和不平衡的树进行进化，有古老或近期的辐射。在具有统计学显著相似性的家族中，约60%的多序列比对与真实比对的相似度达到95%。为了将恢复的拓扑结构与真实拓扑结构进行比较，我们使用了一个反映正确聚类的分支比例的分数。正如预期的那样，在分歧最小的家族中，系统发育的准确性最高。使用贝叶斯、简约、距离和最大似然方法，在具有显著序列相似性的家族中，约88%的系统发育将超过80%的分支聚类。然而，对于具有短古老分支（古老辐射）的蛋白质家族，只有30%的分歧最大（但具有统计学显著性）的家族产生了准确的系统发育，对于第二高度保守的家族，中位数期望值优于10(-60)的，只有约70%产生了准确的树。这些值代表了具有简单分歧历史的序列的预期树准确性的上限；来自700个贾第虫家族的蛋白质，具有相似的序列相似性范围但间隙更多，产生的树准确性要低得多。对于我们模拟的插入和缺失，正确的多序列比对并不比T-COFFEE产生的比对好多少，并且包含具有表达序列标签样测序错误的序列并没有显著降低系统发育准确性。一般来说，虽然分歧较小的序列家族产生的树更准确，但估计准确树的可能性最取决于家族中的辐射是古老的还是近期的。在创建物种树时通过组合来自同一生物体的基因，或者在综合研究中通过选择具有最佳自展值的蛋白质家族，可以提高准确性。
