Department of Computer Science and Engineering, University of Connecticut, Storrs, CT, 06269, USA.
Institute for Systems Genomics, University of Connecticut, Storrs, CT, 06269, USA.
BMC Bioinformatics. 2018 Aug 13;19(Suppl 9):290. doi: 10.1186/s12859-018-2269-0.
Duplication-Transfer-Loss (DTL) reconciliation is a powerful and increasingly popular technique for studying the evolution of microbial gene families. DTL reconciliation requires the use of rooted gene trees to perform the reconciliation with the species tree, and the standard technique for rooting gene trees is to assign a root that results in the minimum reconciliation cost across all rootings of that gene tree. However, even though it is well understood that many gene trees have multiple optimal roots, only a single optimal root is randomly chosen to create the rooted gene tree and perform the reconciliation. This remains an important overlooked and unaddressed problem in DTL reconciliation, leading to incorrect evolutionary inferences. In this work, we perform an in-depth analysis of the impact of uncertain gene tree rooting on the computed DTL reconciliation and provide the first computational tools to quantify and negate the impact of gene tree rooting uncertainty on DTL reconciliation.
Our analysis of a large data set of over 4500 gene families from 100 species shows that a large fraction of gene trees have multiple optimal rootings, that these multiple roots often, but not always, appear closely clustered together in the same region of the gene tree, that many aspects of the reconciliation remain conserved across the multiple rootings, that gene tree error has a profound impact on the prevalence and structure of multiple optimal rootings, and that there are specific interesting patterns in the reconciliation of those gene trees that have multiple optimal roots.
Our results show that unrooted gene trees can be meaningfully reconciled and high-quality evolutionary information can be obtained from them even after accounting for multiple optimal rootings. In addition, the techniques and tools introduced in this paper make it possible to systematically avoid incorrect evolutionary inferences caused by incorrect or uncertain gene tree rooting. These tools have been implemented in the phylogenetic reconciliation software package RANGER-DTL 2.0, freely available from http://compbio.engr.uconn.edu/software/RANGER-DTL/ .
复制-转移-缺失（DTL）协调是研究微生物基因家族进化的强大且越来越流行的技术。DTL 协调需要使用有根基因树来与物种树进行协调，而有根基因树的标准技术是分配一个根，该根在所有该基因树的根中产生最小的协调成本。然而，尽管人们已经很好地理解许多基因树有多个最优根，但只有一个最优根是随机选择的，用于创建有根基因树并执行协调。这仍然是 DTL 协调中一个重要但被忽视和未解决的问题，导致错误的进化推论。在这项工作中，我们对不确定基因树扎根对计算 DTL 协调的影响进行了深入分析，并提供了第一个计算工具来量化和消除基因树扎根不确定性对 DTL 协调的影响。
我们对来自 100 个物种的超过 4500 个基因家族的大型数据集的分析表明，很大一部分基因树有多个最优根，这些多个根通常但不总是紧密聚集在一起在基因树的同一区域，许多协调方面在多个根中保持不变，基因树错误对多个最优根的出现和结构有深远的影响，并且在具有多个最优根的那些基因树的协调中存在特定的有趣模式。
我们的结果表明，即使考虑到多个最优根，无根基因树也可以有意义地协调，并且可以从它们中获得高质量的进化信息。此外，本文介绍的技术和工具使得可以系统地避免由于不正确或不确定的基因树扎根而导致的不正确的进化推论。这些工具已在系统发育协调软件包 RANGER-DTL 2.0 中实现，可从 http://compbio.engr.uconn.edu/software/RANGER-DTL/ 免费获得。
