Leptospirosis is an emerging zoonotic and neglected disease across the world causing huge loss of life and economy. The disease is caused by Leptospira of which 605 sequenced genomes representing 72 species are available in RefSeq database. A comparative genomics approach based on Average Amino acid Identity (AAI), Average Nucleotide Identity (ANI), and Insilco DNA-DNA hybridization provide insight that taxonomic and evolutionary position of few genomes needs to be changed and reclassified. Clustering on the basis of AAI of core and pan-genome contradict clustering pattern on basis of ANI into 4 clusters. Amino acid identity based hierarchical clustering clearly established 3 clusters of Leptospira correlating with level of virulence. Whole genome tree supported three cluster classifications and grouped Leptospira into three clades termed as pathogenic, intermediate and saprophytic. Leptospira genus consist of diverse species and exist in heterogeneous environment, it contains relatively large and closed core genome of 1038 genes. Analysis provided pan genome remains open with 20822 genes. COG analysis revealed that mobilome related genes were found mainly in pan-genome of pathogenic clade. Clade specific genes mined in the study can be used as marker for determining clade and associating level of virulence of any new Leptospira species. Many known Leptospira virulent genes were absent in set of 78 virulent factors mined using Virulence Factor database. A deep search approach provided a repertoire of 496 virulent genes in pan-genome. Further validation of virulent genes will help in accurately targeting pathogenic Leptospira and controlling leptospirosis.

中文翻译：

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钩端螺旋体全基因组序列的比较分析。RefSeq数据库提供的种间差异和毒力因子库

钩端螺旋体病是一种在世界范围内新兴的人畜共患病和被忽视的疾病，造成了巨大的生命和经济损失。该病是由钩端螺旋体引起的，在RefSeq数据库中有代表72个物种的605个测序基因组。基于平均氨基酸同一性（AAI），平均核苷酸同一性（ANI）和Insilco DNA-DNA杂交的比较基因组学方法提供了洞察力，即需要更改和重新分类少数基因组的分类和进化位置。基于核心和泛基因组的AAI聚类与基于ANI的聚类模式相反，分为4个聚类。基于氨基酸身份的层次聚类清楚地建立了钩端螺旋体的3个与毒力水平相关的簇。全基因组树支持三种簇分类，并将钩端螺旋体分为三个进化枝，分别称为致病菌，中间菌和腐生菌。钩端螺旋体属由不同的物种组成，存在于异质环境中，它包含1038个基因的相对较大且封闭的核心基因组。分析提供的泛基因组仍然开放20822个基因。COG分析表明，与运动组相关的基因主要存在于致病进化枝的泛基因组中。该研究中提取的进化枝特异基因可以用作确定进化枝并关联任何新钩端螺旋体物种毒力水平的标记。使用毒力因子数据库挖掘的78种毒力因子集中缺少许多已知的钩端螺旋体毒力基因。深度搜索方法在泛基因组中提供了496个有毒基因的库。