Replication Data for: Molecular Evolution of Aryl Hydrocarbon Receptor Signaling Pathway Genes

The Aryl hydrocarbon receptor is an ancient transcriptional factor originally discovered as a sensor of dioxin. In addition to its function as receptor of environmental toxicants, it plays an important role in development. Although a significant amount of research has been carried out to understand AHR signal transduction pathway and its involvement in species susceptibility to environmental toxicants, none of them to date has comprehensively studied its evolutionary origins. Studying evolutionary origins of molecules can inform ancestral relationships of genes. Vertebrate genome has been shaped by two rounds of whole-genome duplications (WGD) at the base of vertebrate evolution approximately 600 million years ago (Mya), followed by lineage specific gene losses, which often complicate assignment of functional homology. It is crucial to understand evolutionary origins of this transcription factor and its partners, in order to distinguish orthologs from ancient non-orthologous homologs. In this study, we have investigated evolutionary origins of proteins involved in the AHR pathway. Our results provide evidence of gene loss and duplications, crucial for understanding functional connectivity of human and model species. Multiple studies have shown that 2R-ohnologs (genes and proteins that have survived from the 2R-WGD) are enriched in signaling components relevant to developmental disorders and cancer. Our findings provide a link between AHR pathway’s evolutionary trajectory and its possible mechanistic involvement in pathogenesis.

芳香烃受体（Aryl hydrocarbon receptor）是一种古老的转录因子，最初作为二噁英的特异性传感器被发现。除了作为环境毒物的受体发挥功能外，它在生物体发育过程中同样发挥着关键作用。尽管已有大量研究旨在解析AHR信号转导通路及其在物种对环境毒物易感性中的作用，但迄今为止尚无研究全面探讨其进化起源。对分子进化起源的研究有助于揭示基因的祖先演化关系。脊椎动物基因组的演化历程受到两次全基因组复制（whole-genome duplications, WGD）事件的塑造，该事件发生于脊椎动物进化之初的约6亿年前（Mya），后续又伴随谱系特异性基因丢失事件，这往往会给功能同源性的判定带来复杂挑战。为了区分直系同源物与远古非直系同源同源物，明确该转录因子及其伴侣蛋白的进化起源至关重要。本研究对AHR通路相关蛋白的进化起源进行了系统探究。研究结果为基因丢失与复制事件提供了直接证据，这对理解人类与模式物种的功能关联性至关重要。多项研究表明，2R-ohnolog基因（即经历两轮全基因组复制后得以保留的基因与蛋白质）显著富集于与发育异常和癌症相关的信号组分中。本研究的发现将AHR通路的进化轨迹与其在发病机制中潜在的机制性作用联系了起来。