Genomic Analysis of Lambdoid, TB & Other Bacteriophages

描述(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、进化、生理和发病机制中发挥着重要作用。它们的相对简单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发挥了重要作用。然而，尽管对少数噬菌体进行了深入的研究，但我们对噬菌体多样性、进化和基因组组成的了解充其量也是初级的。 通过噬菌体基因组的比较序列分析，可以阐明噬菌体的多样性和产生新病毒的进化机制。对目前可用的大约85个dsDNA尾部噬菌体基因组序列的分析表明，它们在核苷酸序列水平上非常不同，能够感染共同宿主的一对噬菌体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进行分析时，很明显，虽然噬菌体之间有许多共同的基因，但也有很高比例的先前未识别的序列。因此，噬菌体构成了一个巨大的未被探索的序列信息储存库。 噬菌体基因组是典型的嵌合体，由似乎在整个噬菌体种群中迁移的模块组成。这种嵌合体是由非法和同源重组的组合产生的，由非法事件产生的新的马赛克边界，然后通过同源重组进行重新分类。比较序列分析揭示了这些事件是如何在基因和分子水平上发生的。 已测序的噬菌体基因组总数仍然足够少，不可能解决种群水平的问题，如哪些基因组参与了重组，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度是什么。感染更密切相关细菌宿主的病毒和具有极大基因组(约500kbp)的病毒的更大一组噬菌体基因组信息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病毒和宿主基因组的区别。

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.