Department of Integrative Biology, Oregon State University, Corvallis, OR.
Mol Biol Evol. 2020 May 1;37(5):1342-1349. doi: 10.1093/molbev/msaa008.
Metazoans respond to hypoxic stress via the hypoxia-inducible factor (HIF) pathway, a mechanism thought to be extremely conserved due to its importance in monitoring cellular oxygen levels and regulating responses to hypoxia. However, recent work revealed that key members of the HIF pathway have been lost in specific lineages (a tardigrade and a copepod), suggesting that this pathway is not as widespread in animals as previously assumed. Using genomic and transcriptomic data from 70 different species across 12 major crustacean groups, we assessed the degree to which the gene HIFα, the master regulator of the HIF pathway, was conserved. Mining of protein domains, followed by phylogenetic analyses of gene families, uncovered group-level losses of HIFα, including one across three orders within Cirripedia, and in three orders within Copepoda. For these groups, additional assessment showed losses of HIF repression machinery (EGLN and VHL). These results suggest the existence of alternative mechanisms for cellular response to low oxygen and highlight these taxa as models useful for probing these evolutionary outcomes.
后生动物通过缺氧诱导因子 (HIF) 途径对低氧应激做出反应，该机制因其在监测细胞氧水平和调节对低氧反应方面的重要性而被认为是极其保守的。然而，最近的研究表明，HIF 途径的关键成员在特定谱系（水熊虫和桡足类动物）中已经丢失，这表明该途径在动物中的分布并不像以前假设的那样广泛。利用来自 12 个主要甲壳动物群的 70 个不同物种的基因组和转录组数据，我们评估了 HIF 途径的主调控因子 HIFα 的基因在多大程度上得到了保守。通过对蛋白质结构域进行挖掘，然后对基因家族进行系统发育分析，我们发现 HIFα 在群体水平上发生了丢失，包括在甲壳动物门的三个目中，以及在桡足类动物门的三个目中。对于这些群体，进一步的评估表明，HIF 抑制机制（EGLN 和 VHL）也发生了丢失。这些结果表明存在细胞对低氧反应的替代机制，并突出了这些分类群作为探究这些进化结果的有用模型。
