Protocols for the Molecular Evolutionary Analysis of Membrane Protein Gene Duplicates
Protocols for the Molecular Evolutionary Analysis of Membrane Protein Gene Duplicates
复制标题
膜蛋白基因重复分子进化分析方案
DOI：
10.1007/978-1-4939-8736-8_3
复制
发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Liberles, David A.
中科院分区：
文献类型：
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作者：
Yohe, Laurel R.;Liu, Liang;Davalos, Liliana M.;Liberles, David A.
基因复制是真核基因组中基因内容进化的重要过程。了解基因重复何时通过分子适应为基因组贡献新的分子功能是比较基因组学的一个重要目标。然而，在大型基因家族中，表征跨物种的适应和新功能化具有挑战性，因为模型传统上量化重复的时间，而不考虑潜在的基因树。该协议结合了多种方法来检测系统发育规模上蛋白质重复的适应性。我们提供了基因树-物种树协调模型的描述，这些模型能够实现不同类型的推理，以及其使用的实用指南。尽管基于模拟的方法成功地检测了复制/保留率的变化，但复制和保留过程之间的合并、非功能化、亚功能化和新功能化下重复的不同轨迹以及剂量效应提供了迄今为止尚未探索的分析途径。我们引入了这些概率的数学描述，并提供了计算实现的路线图，其起点是简约协调。基于非同义与同义核苷酸取代率 (dN/dS) 之比的序列进化信息可以与重复存活概率相结合，以更好地预测保留重复中新分子功能的出现。总之，这些方法能够表征潜在的适应性候选重复，其新功能化可能有助于跨物种的表型分化。
Gene duplication is an important process in the evolution of gene content in eukaryotic genomes. Understanding when gene duplicates contribute new molecular functions to genomes through molecular adaptation is one important goal in comparative genomics. In large gene families, however, characterizing adaptation and neofunctionalization across species is challenging, as models have traditionally quantified the timing of duplications without considering underlying gene trees. This protocol combines multiple approaches to detect adaptation in protein duplicates at a phylogenetic scale. We include a description of models for gene tree-species tree reconciliation that enable different types of inference, as well as a practical guide to their use. Although simulation-based approaches successfully detect shifts in the rate of duplication/retention, the conflation between the duplication and retention processes, the distinct trajectories of duplicates under non-, sub-, and neofunctionalization, as well as dosage effects offer hitherto unexplored analytical avenues. We introduce mathematical descriptions of these probabilities and offer a road map to computational implementation whose starting point is parsimony reconciliation. Sequence evolution information based on the ratio of nonsynonymous to synonymous nucleotide substitution rates (dN/dS) can be combined with duplicate survival probabilities to better predict the emergence of new molecular functions in retained duplicates. Together, these methods enable characterization of potentially adaptive candidate duplicates whose neofunctionalization may contribute to phenotypic divergence across species.