Novel Integrative Genetic Elements of Mycoplasmas

支原体的新整合遗传元件

• 批准号: 6370243
• 负责人: MICHAEL J CALCUTT
• 金额: $ 18.13万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-06-01 至 2004-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6370243
• 关键词: DNA binding protein; Escherichia coli; Mycoplasma; bacterial genetics; gene mutation; genetic regulation; genetic regulatory element; molecular cloning; open reading frames; site directed mutagenesis

DESCRIPTION (provided by applicant): Although horizontal gene transfer by plasmids and bacteriophages has long been known to disseminate key traits among bacterial populations, only recently has the contribution of mobile chromosomal elements been fully realized. Large chromosomal "islands" that confer pathogenic, symbiotic or metabolic traits have been described, some of which can be conjugated between bacteria. Other important integrated elements exist and the term CONSTIN has been proposed to describe those that are conjugal self-transmissible integrating elements. Studies of the distribution of these diverse elements, their ability to exchange genetic information and their potential to alter the phenotype of an organism by en bloc transfer of discrete gene functions, are still in their relative infancy. Some CONSTINs integrate site-specifically; others are less restricted in their choice of insertion site. The latter may profoundly influence chromosome structure and dynamics, and modulate gene function via mutational changes accompanying promiscuous integration. Recently, distinctive CONSTIN-like elements were identified in two pathogenic mycoplasmas, M. fermentans and M. capricolum. The two elements share features including the presence of conjugation-like genes, flanking direct repeats and a non-replicative extrachromosomal form. Importantly, most genes on these unusual elements lack recognizable homologs and a gene encoding a recognizable DNA integration enzyme is not present. It is anticipated therefore, that a "novel" enzyme performs this integration/excision function. Mycoplasmas typically occupy host niches for long periods during chronic infections in diverse vertebrates, and therefore may serve as important reservoirs for this "novel" element. This underscores the need to understand the dynamics of these elements both within chromosomes of mycoplasmas and in the context of the exchange of mobile gene pools within a population. Accordingly, the specific aims of this proposal are designed (i) to assess the distribution and genomic context of the M. capricolum element in host-related mycoplasmas; (ii) to test the hypothesis that the element is indeed capable of chromosomal integration, and (iii) to explore possible DNA-protein interactions within the termini of the element, as these are predicted to play a critical role in mobility. Completion of these goals will increase our understanding of the function of these novel elements and will provide a platform from which the long term objectives, of understanding their capacity for intra- or inter-species gene transfer, their contribution to the observed plasticity of mycoplasma genomes and their possible role in pathogenesis, can be explored.

描述（由申请人提供）：虽然水平基因转移是通过 质粒和噬菌体长期以来一直被认为是传播关键性状， 细菌种群，直到最近才有移动的染色体的贡献， 要素已全部实现。大的染色体“岛”， 致病性、共生性或代谢性特征，其中一些 可以在细菌之间结合。存在其他重要的综合要素 CONSTIN这个词被用来描述那些 自传递积分元件。研究这些分布 不同的元素，它们交换遗传信息的能力， 通过整体转移离散的 基因功能，仍然处于相对的婴儿期。一些CONSTIN集成 位点特异性;其他人在插入选择方面限制较少 绝佳的价钱后者可能深刻地影响染色体结构和动力学， 并通过伴随滥交的突变来调节基因功能 一体化最近，在两个细胞中发现了独特的CONSTIN样元件， 致病性支原体，M. fermentans和M.摩羯座这两个元素共享 特征包括存在接合样基因，侧翼直接连接， 重复和非复制染色体外形式。重要的是，大多数基因 这些不寻常的元素缺乏可识别的同源物， 不存在可识别的DNA整合酶。预计 因此“新的”酶执行这种整合/切除功能。 支原体通常在慢性感染期间长时间占据宿主小生境。 感染在不同的脊椎动物，因此可能作为重要的 这种“新”元素的储存库。这强调了了解的必要性 这些元件在支原体染色体内和 一个种群中移动的基因库交换的背景。 因此，本建议的具体目标是：㈠评估 分布和基因组背景。寄主相关的摩羯座因子 支原体;（ii）测试该元素确实能够 染色体整合，以及（iii）探索可能的DNA-蛋白质相互作用 在元素的终端内，因为这些被预测将发挥关键作用， 流动性的作用。这些目标的实现将增加我们对 这些新元素的功能，并将提供一个平台， 长期目标，了解他们的能力， 种间基因转移，它们对观察到的 支原体基因组及其在发病机制中的可能作用。