Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Byblos, Lebanon.
Department of Pathology and Laboratory Medicine, American University of Beirut, Beirut, Lebanon.
PLoS Negl Trop Dis. 2020 Sep 18;14(9):e0008684. doi: 10.1371/journal.pntd.0008684. eCollection 2020 Sep.
Leishmania tropica is one of the main causative agents of cutaneous leishmaniasis (CL). Population structures of L. tropica appear to be genetically highly diverse. However, the relationship between L. tropica strains genomic diversity, protein coding gene evolution and biogeography are still poorly understood. In this study, we sequenced the genomes of three new clinical L. tropica isolates, two derived from a recent outbreak of CL in camps hosting Syrian refugees in Lebanon and one historical isolate from Azerbaijan to further refine comparative genome analyses. In silico multilocus microsatellite typing (MLMT) was performed to integrate the current diversity of genome sequence data in the wider available MLMT genetic population framework. Single nucleotide polymorphism (SNPs), gene copy number variations (CNVs) and chromosome ploidy were investigated across the available 18 L. tropica genomes with a main focus on protein coding genes. MLMT divided the strains in three populations that broadly correlated with their geographical distribution but not populations defined by SNPs. Unique SNPs profiles divided the 18 strains into five populations based on principal component analysis. Gene ontology enrichment analysis of the protein coding genes with population specific SNPs profiles revealed various biological processes, including iron acquisition, sterols synthesis and drug resistance. This study further highlights the complex links between L. tropica important genomic heterogeneity and the parasite broad geographic distribution. Unique sequence features in protein coding genes identified in distinct populations reveal potential novel markers that could be exploited for the development of more accurate typing schemes to further improve our knowledge of the evolution and epidemiology of the parasite as well as highlighting protein variants of potential functional importance underlying L. tropica specific biology.
热带利什曼原虫是皮肤利什曼病（CL）的主要病原体之一。热带利什曼原虫的种群结构在遗传上似乎高度多样化。然而，利什曼原虫株基因组多样性、蛋白质编码基因进化和生物地理学之间的关系仍知之甚少。在这项研究中，我们对三个新的临床热带利什曼原虫分离株的基因组进行了测序，其中两个分离株来自黎巴嫩难民营中最近一次 CL 爆发，一个分离株来自阿塞拜疆，以进一步完善比较基因组分析。通过体外多位点微卫星分型（MLMT），将当前的基因组序列数据多样性整合到更广泛的可用 MLMT 遗传群体框架中。在可用的 18 个热带利什曼原虫基因组中，我们研究了单核苷酸多态性（SNPs）、基因拷贝数变异（CNVs）和染色体倍性，主要集中在蛋白质编码基因上。MLMT 将菌株分为三个群体，这些群体与它们的地理分布大致相关，但与 SNP 定义的群体无关。基于主成分分析的独特 SNP 图谱将 18 个菌株分为五个群体。对具有群体特异性 SNP 图谱的蛋白质编码基因进行基因本体论富集分析，揭示了各种生物学过程，包括铁获取、固醇合成和药物抗性。本研究进一步强调了热带利什曼原虫重要基因组异质性与寄生虫广泛地理分布之间的复杂联系。在不同群体中鉴定出的蛋白质编码基因的独特序列特征揭示了潜在的新标记，这些标记可用于开发更准确的分型方案，以进一步提高我们对寄生虫进化和流行病学的认识，并突出潜在功能重要性的蛋白质变异体，这些变异体是热带利什曼原虫特有的生物学基础。
