Genome Variability and Population Processes of Lyme Disease Pathogens

描述（由申请人提供）：进化基因组学是通过识别病原体基因组中的毒力基因和揭示疾病传播的模式和机制来控制新发传染病的关键。莱姆病是北美和欧洲最常见的媒介传播疾病，由属于伯氏疏螺旋体细菌复合体的病原体引起。虽然地理位置有限，但莱姆病的流行范围在近几十年来已大大扩大，几乎无法预测。在过去的四年里，PI和他的合作者已经对23种世界范围内具有代表性的莱姆病病原体菌株进行了基因组测序。与之前由本研究小组和其他研究小组测序的六个基因组一起，大量的伯氏疏螺旋体基因组通过进化和比较基因组学开启了了解莱姆病地方性基因组和生态基础的新时代。在1998- 2012年期间，SC3的支持是PI在基于系统发育的菌株全基因组测序选择，广泛重组的发现和估计其率，以及由少数主要表面抗原位点和外表面蛋白C （ospC）位点的免疫逃逸驱动的伯氏疏螺旋体基因组多样性计算模型的主要作用背后的主导作用。此外，SC3项目在PI的实验室中形成了成熟的生物信息学和分析基础设施，包括定制的基因组数据库，一套

DESCRIPTION (provided by applicant): Evolutionary genomics is a key to controlling emerging infectious diseases by identifying virulence genes in the pathogen genome and by revealing patterns and mechanisms of disease spread. Lyme disease, caused by pathogens belonging to the bacterial species complex Borrelia burgdorferi sensu lato, is the most common vector-borne disease in North America and Europe. Although geographically limited, the Lyme disease endemic has greatly expanded in range in recent decades with little predictability. In the past four years, the PI and his collaborators have sequenced the genomes of twenty-three world-wide representative strains of Lyme disease pathogens. Along with the half dozen genomes previously sequenced by this and other research groups, this large amount of Borrelia genomes usher in a new era of understanding the genomic and ecological basis of Lyme disease endemics through evolutionary and comparative genomics. The SC3 support during 1998- 2012 is behind the PI's leading roles in the phylogeny-based selection of strains for whole-genome sequencing, the discovery of widespread recombination and estimation of its rates, and the development of a computational model of B. burgdorferi genome diversity driven by immune escape at a few major surface antigen loci and the outer-surface protein C (ospC) locus in particular. In addition, the SC3 projects resulted in a mature bioinformatics and analytical infrastructure in the PI's lab including, e.g., a customized genome database, a suite of Perl/BioPerl based software tools ("DNATweezers"), and a simulator of bacterial genome evolution ("SimBac"). The latter two tools have been released into public repository SourceForge.net as Open Source projects. The PI's specific aims for the proposed SC1 project are to (i) reveal genome variability associated with B. burgdorferi virulence by tests of positive and purifying natural selection, (ii) launch a new line of research in the phylodynamics of Borrelia for predicting the spread of Lyme endemics, and (iii) modernize comparative genomics studies of pathogens by develop evolutionary bioinformatics tools. The PI will develop non-SCORE research proposals through widening collaboration with Borrelia molecular geneticists and Lyme ecologists and developing translational and innovative research programs in population genomics of Lyme disease. To summarize, the overall goal and expected outcomes of the project will be an elucidation of virulence-associated genomic variations, predictive models of the spread of Lyme disease endemics, and a nationally competitive research program in ecology and evolution of emerging infectious diseases. The project helps to control the spread of Lyme disease by identifying virulence genes and by predicting pathogen spread in nature.