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Abstract：
Genome assemblies provide a powerful basis of comparative multi-omics analyses that offer insight into parasite pathogenicity, host-parasite interactions, and invasion biology. As a unique intracellular nematode, Trichinella consists of two clades, encapsulated and non-encapsulated. Genomic correlation of the distinct differences between the two clades is still unclear. Here, we report an annotated draft reference genome of non-encapsulated Trichinella, T. pseudospiralis, and perform comparative multi-omics analyses with encapsulated T. spiralis. Genome and methylome analyses indicate that, during Trichinella evolution, the two clades of Trichinella exhibit differential expansion and methylation of parasitism-related multi-copy gene families, especially for the DNase II members of the phospholipase D superfamily and Glutathione S-transferases. Further, methylome and transcriptome analyses revealed divergent key excretory/secretory (E/S) genes between the two clades. Among these key E/S genes, TP12446 is significantly more expressed across three life stages in T. pseudospiralis. Overexpression of TP12446 in the mouse C2C12 skeletal muscle cell line could induce inhibition of myotube formation and differentiation, further indicating its key role in parasitism of T. pseudospiralis. This multi-omics study provides a foundation for further elucidation of the mechanism of nurse cell formation and immunoevasion, as well as the identification of pharmacological and diagnostic targets of trichinellosis.
摘要：
基因组组装提供了一个强大的基础比较多组学分析，提供洞察寄生虫的致病性，宿主-寄生虫相互作用，入侵生物学。作为一种独特的细胞内线虫，旋毛虫由两个分支组成，封装和非封装。两种进化枝之间明显差异的基因组相关性仍不清楚。这里,我们报告了一个注释的非包囊旋毛虫的参考基因组草案，假螺旋体，并与包封的旋毛虫进行比较多组学分析。基因组和甲基化组分析表明，在旋毛虫进化过程中，旋毛虫的两个分支表现出与寄生相关的多拷贝基因家族的差异扩增和甲基化，特别是对于磷脂酶D超家族的DNaseII成员和谷胱甘肽S-转移酶。Further,甲基化组和转录组分析揭示了两个进化枝之间不同的关键排泄/分泌（E/S）基因。在这些关键的E/S基因中，TP12446在假螺旋藻的三个生命阶段中显著更多表达。在小鼠C2C12骨骼肌细胞系中过表达TP12446可以诱导肌管形成和分化的抑制，进一步表明其在假螺旋藻寄生中的关键作用。这项多组学研究为进一步阐明护士细胞形成和免疫逃避的机制奠定了基础，以及旋毛虫病的药理和诊断目标的确定。
