背景:基因复制被认为是进化中获得新功能的核心过程。重复后决定基因保留的因素以及序列中的同源基因差异,表达和功能已被广泛研究。然而,关于基因重复的启动子区域的进化以及它们如何影响基因重复差异的知识相对较少。这里,我们专注于同源基因的启动子,比较它们在序列上的相似性,在结合它们的转录因子(TF)组中,以及他们的整体发起人架构。
结果:我们观察到最近重复的启动子之间显示出更高的序列相似性,并且更古老的旁系同源启动子之间的序列相似性迅速下降。相比之下,在顺式调节方面相似,如通过结合两个旁系同源物的启动子的TFs集合所测量的,不会简单地从复制中随着时间的推移而减少,而是与启动子结构相关-CpG岛(CGI)在其启动子中共享更大比例的TFs,而无CGI的旁系同源物在其TF结合集中更不同。专注于最近的复制事件并通过其复制机制对其进行分区,使我们能够发现与基因保留相关的启动子特性,以及表征新生基因启动子的进化:在最近的反转座介导的重复中,我们观察到同源物对的顺式调节中的不对称性:逆转录基因表达低,其启动子被较少的TF结合,并耗尽CGI,与原始基因拷贝相比。此外,观察灵长类动物最近的分段重复区域,使我们能够比较成功的保留和重复的丢失,表明重复保留与较少的TF和无CGI启动子结构相关。
结论:在这项工作中,我们分析了基因重复的启动子及其同源物之间的差异。我们还研究了它们的特征如何与复制时间和复制机制相关联,以及这些复制品的命运。这些结果强调了顺式调控机制在塑造新基因的进化及其复制后命运中的重要性。
Gene duplication is thought to be a central process in evolution to gain new functions. The factors that dictate gene retention following duplication as well paralog gene divergence in sequence, expression and function have been extensively studied. However, relatively little is known about the evolution of promoter regions of gene duplicates and how they influence gene duplicate divergence. Here, we focus on promoters of paralog genes, comparing their similarity in sequence, in the sets of transcription factors (TFs) that bind them, and in their overall promoter architecture.
We observe that promoters of recent duplications display higher sequence similarity between them and that sequence similarity rapidly declines between promoters of more ancient paralogs. In contrast, similarity in cis-regulation, as measured by the set of TFs that bind promoters of both paralogs, does not simply decrease with time from duplication and is instead related to promoter architecture-paralogs with CpG Islands (CGIs) in their promoters share a greater fraction of TFs, while CGI-less paralogs are more divergent in their TF binding set. Focusing on recent duplication events and partitioning them by their duplication mechanism enables us to uncover promoter properties associated with gene retention, as well as to characterize the evolution of promoters of newly born genes: In recent retrotransposition-mediated duplications, we observe asymmetry in cis-regulation of paralog pairs: Retrocopy genes are lowly expressed and their promoters are bound by fewer TFs and are depleted of CGIs, in comparison with the original gene copy. Furthermore, looking at recent segmental duplication regions in primates enable us to compare successful retentions versus loss of duplicates, showing that duplicate retention is associated with fewer TFs and with CGI-less promoter architecture.
In this work, we profiled promoters of gene duplicates and their inter-paralog divergence. We also studied how their characteristics are associated with duplication time and duplication mechanism, as well as with the fate of these duplicates. These results underline the importance of cis-regulatory mechanisms in shaping the evolution of new genes and their fate following duplication.