关键词: Naegleria Naegleria fowleri virulence-associated genes core genome free-living amoebae genome plasticity pangenome species-specific genes whole genome sequencing

来  源:   DOI:10.3389/fmicb.2022.1056418   PDF(Pubmed)

Abstract:
UNASSIGNED: Free-living amoebae of the Naegleria genus belong to the major protist clade Heterolobosea and are ubiquitously distributed in soil and freshwater habitats. Of the 47 Naegleria species described, N. fowleri is the only one being pathogenic to humans, causing a rare but fulminant primary amoebic meningoencephalitis. Some Naegleria genome sequences are publicly available, but the genetic basis for Naegleria diversity and ability to thrive in diverse environments (including human brain) remains unclear.
UNASSIGNED: Herein, we constructed a high-quality Naegleria genus pangenome to obtain a comprehensive catalog of genes encoded by these amoebae. For this, we first sequenced, assembled, and annotated six new Naegleria genomes.
UNASSIGNED: Genome architecture analyses revealed that Naegleria may use genome plasticity features such as ploidy/aneuploidy to modulate their behavior in different environments. When comparing 14 near-to-complete genome sequences, our results estimated the theoretical Naegleria pangenome as a closed genome, with 13,943 genes, including 3,563 core and 10,380 accessory genes. The functional annotations revealed that a large fraction of Naegleria genes show significant sequence similarity with those already described in other kingdoms, namely Animalia and Plantae. Comparative analyses highlighted a remarkable genomic heterogeneity, even for closely related strains and demonstrate that Naegleria harbors extensive genome variability, reflected in different metabolic repertoires. If Naegleria core genome was enriched in conserved genes essential for metabolic, regulatory and survival processes, the accessory genome revealed the presence of genes involved in stress response, macromolecule modifications, cell signaling and immune response. Commonly reported N. fowleri virulence-associated genes were present in both core and accessory genomes, suggesting that N. fowleri\'s ability to infect human brain could be related to its unique species-specific genes (mostly of unknown function) and/or to differential gene expression. The construction of Naegleria first pangenome allowed us to move away from a single reference genome (that does not necessarily represent each species as a whole) and to identify essential and dispensable genes in Naegleria evolution, diversity and biology, paving the way for further genomic and post-genomic studies.
摘要:
UNASSIGNED:Naegleria属的自由生活变形虫属于主要的原生进化枝杂种,并普遍分布在土壤和淡水栖息地中。在所描述的47种Naegleria物种中,N.Fowleri是唯一对人类有致病性的,引起罕见但暴发性原发性阿米巴脑膜脑炎。一些Naegleria基因组序列是公开的,但是Naegleria多样性和在不同环境(包括人脑)中茁壮成长的能力的遗传基础仍不清楚。
未经批准:此处,我们构建了高质量的Naegleria属pangenome,以获得这些变形虫编码的基因的综合目录。为此,我们首先测序,组装,并注释了六个新的Naegleria基因组。
UNASSIGNED:基因组结构分析表明,Naegleria可能利用基因组可塑性特征,如倍性/非整倍体来调节它们在不同环境中的行为。当比较14个接近完整的基因组序列时,我们的结果估计理论上的Naegleriapangenome是一个封闭的基因组,有13,943个基因,包括3,563个核心基因和10,380个辅助基因。功能注释表明,大部分Naegleria基因与其他王国中已经描述的基因显示出显着的序列相似性,即动物和植物。比较分析强调了显著的基因组异质性,即使是密切相关的菌株,并证明Naegleria具有广泛的基因组变异性,反映在不同的代谢库中。如果Naegleria核心基因组富含代谢必需的保守基因,管理和生存过程,辅助基因组揭示了与应激反应有关的基因的存在,大分子修饰,细胞信号和免疫反应。常见报道的牛牛毒力相关基因存在于核心和辅助基因组中,这表明N.fowleri感染人脑的能力可能与其独特的物种特异性基因(主要是未知功能)和/或差异基因表达有关。Naegleria第一个pangenome的构建使我们能够摆脱单个参考基因组(不一定代表整个物种),并确定Naegleria进化中必不可少的和可有可无的基因,多样性和生物学,为进一步的基因组和后基因组研究铺平道路。
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