Genomic Analysis of Lambdoid, TB & Other Bacteriophages

Lambdoid 的基因组分析，TB

• 批准号: 7099514
• 负责人: ROGER W HENDRIX
• 金额: $ 42.6万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-01-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7099514
• 关键词: bacterial DNA; bacterial genetics; bacterial virus; bacteriophage lambda; biochemical evolution; bioinformatics; biotechnology; computational biology; computer assisted sequence analysis; computer program /software; computer system design /evaluation; functional /structural genomics; genetic polymorphism; genetic recombination; genome; host organism interaction; microorganism interaction; nucleic acid sequence; virus DNA; virus genetics

DESCRIPTION (provided by applicant): Bacteriophages are the most numerous organisms in the biosphere and play major roles in the ecology, evolution, physiology and pathogenesis of their bacterial hosts. Their relative simplicity makes them terrific model systems and they have been instrumental in the development of molecular biology and the biotechnology industry. Nevertheless, notwithstanding the in-depth studies on a small number of bacteriophages, our understanding of phage diversity, evolution and genomic constitution is rudimentary at best. Elucidation of bacteriophage diversity and the evolutionary mechanisms that generate new viruses can be investigated by comparative sequence analysis of phage genomes. Analysis of the currently available sequences of approximately 85 genomes of dsDNA tailed phages reveals that they are extremely diverse at the nucleotide sequence level and that pairs of phages competent to infect a common host do not necessarily share any significant DNA sequence homology. When analyzed at the amino acid sequence level it is apparent that while there are many genes shared among phages, there are also a high proportion of previously unidentified sequences. Bacteriophages therefore constitute a huge reservoir of unexplored sequence information. Bacteriophage genomes are characteristically mosaic, composed of modules that appear to migrate throughout the phage population. This mosaicism is generated by a combination of illegitimate and homologous recombination, with novel mosaic boundaries generated by illegitimate events, which are then reassorted by homologous recombination. Comparative sequence analysis reveals insights into how these events occur at the genetic and molecular levels. The total number of sequenced phage genomes is still sufficiently small that it is not possible to address population level questions, such as which genomes are participating in recombination and what is the direction and rate of gene flow between phages and between phages and their hosts. A larger set of phage genomic information of viruses that infect more closely-related bacterial hosts and of viruses with extremely large genomes (approximately 500kbp) will reveal how phages evolve, how they influence the evolution of their hosts, and what - at the most fundamental level - distinguishes viral and host genomes.

描述（由申请人提供）：噬菌体是生物圈中数量最多的生物体，在其细菌宿主的生态学、进化、生理学和发病机制中发挥重要作用。它们的相对简单性使它们成为极好的模型系统，它们在分子生物学和生物技术工业的发展中起着重要作用。然而，尽管对少量噬菌体进行了深入研究，但我们对噬菌体多样性，进化和基因组构成的理解充其量是初步的。 噬菌体多样性的阐明和产生新病毒的进化机制可以通过噬菌体基因组的比较序列分析来研究。对目前可获得的约85个双链DNA尾噬菌体基因组序列的分析表明，它们在核苷酸序列水平上极其多样，并且能够感染共同宿主的噬菌体对不一定具有任何显著的DNA序列同源性。当在氨基酸序列水平上分析时，很明显，虽然有许多基因在哺乳动物中共享，但也有很高比例的先前未鉴定的序列。因此，噬菌体构成了一个巨大的未开发的序列信息库。 噬菌体基因组是典型的马赛克，由似乎在整个噬菌体群体中迁移的模块组成。这种镶嵌现象是由非法和同源重组的组合产生的，非法事件产生了新的镶嵌边界，然后通过同源重组重新排列。比较序列分析揭示了这些事件在遗传和分子水平上是如何发生的。 测序的噬菌体基因组的总数仍然足够小，不可能解决群体水平的问题，例如哪些基因组参与重组，以及噬菌体之间以及噬菌体与其宿主之间的基因流动的方向和速率是什么。一组更大的病毒噬菌体基因组信息，感染更密切相关的细菌宿主和具有极大基因组（约500 kbp）的病毒，将揭示噬菌体如何进化，它们如何影响宿主的进化，以及在最基本的水平上区分病毒和宿主基因组的是什么。