Comparing a parasitic lineage to its free-living relatives is a powerful way to understand how that evolutionary transition to parasitism occurred. Giardia intestinalis (Fornicata) is a leading cause of gastrointestinal disease world-wide and is famous for its unusual complement of cellular compartments, such as having peripheral vacuoles instead of typical endosomal compartments. Endocytosis plays an important role in Giardia’s pathogenesis. Endosomal sorting complexes required for transport (ESCRT) are membrane-deforming proteins associated with the late endosome/multivesicular body (MVB). MVBs are ill-defined in G. intestinalis, and roles for identified ESCRT-related proteins are not fully understood in the context of its unique endocytic system. Furthermore, components thought to be required for full ESCRT functionality have not yet been documented in this species. We used genomic and transcriptomic data from several Fornicata species to clarify the evolutionary genome streamlining observed in Giardia, as well as to detect any divergent orthologs of the Fornicata ESCRT subunits. We observed differences in the ESCRT machinery complement between Giardia strains. Microscopy-based investigations of key components of ESCRT machinery such as GiVPS36 and GiVPS25 link them to peripheral vacuoles, highlighting these organelles as simplified MVB equivalents. Unexpectedly, we show ESCRT components associated with the endoplasmic reticulum and, for the first time, mitosomes. Finally, we identified the rare ESCRT component CHMP7 in several fornicate representatives, including Giardia and show that contrary to current understanding, CHMP7 evolved from a gene fusion of VPS25 and SNF7 domains, prior to the last eukaryotic common ancestor, over 1.5 billion years ago. Our findings show that ESCRT machinery in G. intestinalis is far more varied and complete than previously thought, associates to multiple cellular locations, and presents changes in ESCRT complement which pre-date adoption of a parasitic lifestyle.

中文翻译：

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肠道贾第鞭毛虫 ESCRT 机器的意外细胞器位置和跨越 Fornicata 谱系向寄生过渡的复杂进化动力学

将寄生谱系与其自由生活的亲属进行比较是了解进化过渡到寄生的一种强有力的方法。肠贾第鞭毛虫 (Fornicata) 是全球胃肠道疾病的主要原因，并以其不寻常的细胞隔室补充而闻名，例如具有外周液泡而不是典型的内体隔室。胞吞作用在贾第虫的发病机制中起重要作用。转运所需的内体分选复合物 (ESCRT) 是与晚期内体/多泡体 (MVB) 相关的膜变形蛋白。MVB 在肠胃大肠菌中的定义不明确，并且在其独特的内吞系统的背景下，尚未完全了解已鉴定的 ESCRT 相关蛋白的作用。此外，被认为是完整 ESCRT 功能所需的组件尚未在该物种中记录。我们使用来自几种 Fornicata 物种的基因组和转录组数据来阐明在贾第虫中观察到的进化基因组流线型，以及检测 Fornicata ESCRT 亚基的任何不同的直系同源物。我们观察到贾第鞭毛虫菌株之间 ESCRT 机械补体的差异。对 ESCRT 机器的关键部件（如 GiVPS36 和 GiVPS25）的基于显微镜的研究将它们与外周液泡联系起来，将这些细胞器突出显示为简化的 MVB 等效物。出乎意料的是，我们首次展示了与内质网相关的 ESCRT 成分，并且首次展示了有丝分裂体。最后，我们在几个 fornicate 代表中发现了罕见的 ESCRT 成分 CHMP7，包括贾第鞭毛虫，并表明与目前的理解相反，CHMP7 从 VPS25 和 SNF7 结构域的基因融合进化而来，在最后一个真核生物共同祖先之前，超过 15 亿年前。我们的研究结果表明，肠杆菌中的 ESCRT 机制比以前认为的要多样化和完整得多，与多个细胞位置相关，并且呈现出早于采用寄生生活方式的 ESCRT 补充的变化。