Annotation of the Mycoplasma alligatoris genome

性状（由申请方提供）：支原体是重要的病原体，通常具有严格的天然宿主嗜性，毒力机制知之甚少。这项工作的广泛目标是通过比较支原体基因组的保守和可变特征，增加对支原体宿主范围和毒力决定因素的理解。比较基因组学是一种新的替代分子生物学的常用工具来阐明支原体病的遗传基础。在这项工作中，应优先考虑美洲鳄支原体，因为它在某些宿主中引起超急性致死性疾病，但在其他宿主中仅是寄生虫。具体目标是绘制出M.通过与肺支原体基因组序列比对，对扬子鳄支原体基因组进行同源性分析，并筛选出与嗜性和毒力相关的候选基因。将使用自动化高通量序列组装方法组装工作草案。将通过比较同线性和基于PCR的缺口闭合验证序列比对。编码序列将通过用支原体序列训练的内插马尔可夫模型识别，并根据其公共数据库匹配进行编目。候选宿主范围基因可以通过与已知粘附素的总体相似性或通过签名配体结合基序来识别。毒力因子可以包括与其他柔膜菌的细胞表面或分泌的水解酶或存在于其他细菌中的致病决定簇的同源物。同源物的序列，其已知的生物学作用或预测的特性与宿主细胞表面配体结合或M的致病作用一致。将详细描述鳄鱼的特征。这些数据将被整合在一个代表性的补充粘附，运输和代谢途径的M。通过生物学上充分记录的柔膜菌的代谢图验证了alligatoris。基于PCR的克隆的便利性和生物信息学软件的可访问性使其成为吸引本科生参与创新生物医学研究的理想项目。

DESCRIPTION (provided by applicant): Mycoplasmas are important pathogens with usually strict natural host tropism and poorly understood virulence mechanisms. The broad objective of this work is increased understanding of mycoplasmal host-range and virulence determinants through comparison of conserved and variable features of mycoplasmal genomes. Comparative genomics is a new alternative to the usual tools of molecular biology to elucidate the genetic bases of mycoplasmosis. Mycoplasma alligatoris merits priority in that effort because in some hosts it causes hyperacute lethal disease, but it is merely commensal in others. The specific aims are to assemble a draft map of the M. alligatoris genome by alignment with that of closely-related Mycoplasma pulmonis, and to identify candidate genes involved in host tropism and virulence. The working draft will be assembled by using automated high-throughput sequence assembly methods. Sequence alignments will be validated by comparative synteny and PCR-based gap closure. Coding sequences will be identified by interpolated Markov models trained with mycoplasmal sequences and cataloged according to their public database matches. Candidate host-range genes may be recognized by overall similarity to known adhesins or by signature ligand-binding motifs. Virulence factors may include homologs to cell-surface or secreted hydrolytic enzymes of other mollicutes, or to pathogenic determinants present in other bacteria. The sequences of homologs whose known biological roles or predicted properties are consistent with host cell-surface ligand-binding or the pathogenic effects of M. alligatoris will be characterized in detail. The data will be integrated in a representation of the complement of adhesion, transport, and metabolic pathways of M. alligatoris validated by the biologically well-documented metabolic map of the mollicutes. The ease of PCR-based cloning and the accessibility of bioinformatics software make this an ideal project to engage undergraduate students in innovative biomedical research.