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Abstract：
Leprosy is caused by Mycobacterium leprae and Mycobacterium lepromatosis. We report construction and analyses of the complete genome sequence of M. lepromatosis FJ924. The genome contained 3,271,694 nucleotides to encode 1,789 functional genes and 1,564 pseudogenes. It shared 1,420 genes and 885 pseudogenes (71.4%) with M. leprae but differed in 1,281 genes and pseudogenes (28.6%). In phylogeny, the leprosy bacilli started from a most recent common ancestor (MRCA) that diverged ~30 million years ago (Mya) from environmental organism Mycobacterium haemophilum. The MRCA then underwent reductive evolution with pseudogenization, gene loss, and chromosomal rearrangements. Analysis of the shared pseudogenes estimated the pseudogenization event ~14 Mya, shortly before species bifurcation. Afterwards, genomic changes occurred to lesser extent in each species. Like M. leprae, four major types of highly repetitive sequences were detected in M. lepromatosis, contributing to chromosomal rearrangements within and after MRCA. Variations in genes and copy numbers were noted, such as three copies of the gene encoding bifunctional diguanylate cyclase/phosphodiesterase in M. lepromatosis, but single copy in M. leprae; 6 genes encoding the TetR family transcriptional regulators in M. lepromatosis, but 11 such genes in M. leprae; presence of hemW gene in M. lepromatosis, but absence in M. leprae; and others. These variations likely aid unique pathogenesis, such as diffuse lepromatous leprosy associated with M. lepromatosis, while the shared genomic features should explain the common pathogenesis of dermatitis and neuritis in leprosy. Together, these findings and the genomic data of M. lepromatosis may facilitate future research and care for leprosy. IMPORTANCE Leprosy is a dreaded infection that still affects millions of people worldwide. Mycobacterium lepromatosis is a recently recognized cause in addition to the well-known Mycobacterium leprae. M. lepromatosis is likely specific for diffuse lepromatous leprosy, a severe form of the infection and endemic in Mexico. This study constructed and annotated the complete genome sequence of M. lepromatosis FJ924 and performed comparative genomic analyses with related mycobacteria. The results afford new and refined insights into the genome size, gene repertoire, pseudogenes, phylogenomic relationship, genome organization and plasticity, process and timing of reductive evolution, and genetic and proteomic basis for pathogenesis. The availability of the complete M. lepromatosis genome may prove to be useful for future research and care for the infection.
摘要：
麻风病是由麻风分枝杆菌和麻风分枝杆菌引起的。我们报告了麻风分枝杆菌FJ924的完整基因组序列的构建和分析。基因组包含3,271,694个核苷酸以编码1,789个功能基因和1,564个假基因。它与麻风分枝杆菌共享1,420个基因和885个假基因（71.4％），但在1,281个基因和假基因（28.6％）上有所不同。在系统发育中，麻风病杆菌始于最近的共同祖先（MRCA），该祖先在约3000万年前（Mya）与环境生物嗜血杆菌分离。然后，MRCA经历了伪生成的还原进化，基因丢失，和染色体重排.对共享假基因的分析估计假基因发生事件~14Mya，在物种分叉前不久。之后,每个物种的基因组变化程度较小。像麻风M,在麻风分枝杆菌中检测到四种主要类型的高度重复序列，有助于MRCA内部和之后的染色体重排。注意到基因和拷贝数的变化，例如在麻风分枝杆菌中编码双功能二鸟苷酸环化酶/磷酸二酯酶的基因的三个拷贝，但单拷贝在麻风分枝杆菌中；6个编码麻风分枝杆菌TetR家族转录调节因子的基因，但是麻风分枝杆菌中有11个这样的基因；麻风分枝杆菌中存在hemW基因，但不在麻风M.这些变化可能有助于独特的发病机制，如弥漫性麻风病与麻风病相关，而共同的基因组特征应该解释麻风病皮炎和神经炎的共同发病机理。一起,这些发现和麻风病的基因组数据可能有助于麻风病的未来研究和护理。重要性麻风病是一种可怕的感染，仍然影响着全世界数百万人。除众所周知的麻风分枝杆菌外，麻风分枝杆菌是最近公认的病因。麻风分枝杆菌可能是弥漫性麻风病的特异性，一种严重的感染形式，在墨西哥流行。本研究构建并注释了麻木病分枝杆菌FJ924的完整基因组序列，并与相关分枝杆菌进行了比较基因组分析。这些结果为基因组大小提供了新的和完善的见解，基因库，假基因，系统发育关系，基因组组织和可塑性，还原性进化的过程和时机，以及发病机理的遗传和蛋白质组学基础。完整的麻木病分枝杆菌基因组的可用性可能被证明对未来的研究和感染护理是有用的。
