Abstract:
The family Borreliaceae contains arthropod-borne spirochetes that cause two widespread human diseases, Lyme disease and relapsing fever. Lyme disease is a subacute, progressive illness with variable stage and tissue manifestations. Relapsing fever is an acute febrile illness with prominent bacteremia that may recur and disseminate, particularly to the nervous system. Clinical heterogeneity is a hallmark of both diseases. While human clinical manifestations are influenced by a wide variety of factors, including immune status and host genetic susceptibility, there is evidence that Borreliaceae microbial factors influence the clinical manifestations of human disease caused by this family of spirochetes. Despite these associations, the spirochete genes that influence the severity and manifestations of human disease are, for the most part, unknown. Recent work has identified lineage-specific expansions of lipoproteome-rich accessory genome elements in virulent clones of Borrelia burgdorferi. Using publicly available genome assemblies, it is shown that all Borreliaceae lineages for which sufficient sequence data are available harbor a similar pattern of strongly structured, lineage-specific expansions in their accessory genomes, particularly among lipoproteins, and that this pattern holds across phylogenetic scales including genera, species, and genotypes. The relationships among pangenome elements suggest that infrequent episodes of marked genomic change followed by clonal expansion in geographically and enzootically structured populations may account for the unique lineage structure of Borreliaceae. This analysis informs future genotype-phenotype studies among Borreliaceae and lays a foundation for studies of individual gene function guided by phylogenetic patterns of conservation, diversification, gain, and/or loss.
摘要:
螺旋体科包含节肢动物传播的螺旋体,会导致两种广泛的人类疾病,莱姆病和复发性发热。莱姆病是一种亚急性疾病,具有不同阶段和组织表现的进行性疾病。复发热是一种急性发热性疾病,伴有突出的菌血症,可能会复发和传播,尤其是神经系统。临床异质性是两种疾病的标志。虽然人类的临床表现受多种因素的影响,包括免疫状态和宿主遗传易感性,有证据表明,螺旋体科微生物因素影响由该螺旋体家族引起的人类疾病的临床表现。尽管有这些协会,影响人类疾病严重程度和表现的螺旋体基因是,在大多数情况下,未知。最近的工作已经确定了伯氏疏螺旋体毒力克隆中富含脂蛋白组的辅助基因组元件的谱系特异性扩增。使用公开可用的基因组组装,结果表明,所有可获得足够序列数据的Borreliaceae谱系都具有相似的强结构化模式,其附属基因组中的谱系特异性扩增,特别是在脂蛋白中,这种模式适用于包括属在内的系统发育尺度,物种,和基因型。pangenome元素之间的关系表明,在地理和植物性结构的种群中,罕见的明显基因组变化,随后的克隆扩增可能是疏螺旋体科独特的谱系结构的原因。该分析为婆罗洲科未来的基因型表型研究提供了信息,并为受保守系统发育模式指导的个体基因功能研究奠定了基础。多样化,增益,和/或损失。