Evolution of Intradiol Dioxygenase Genes in Bacteria

细菌内二醇双加氧酶基因的进化

• 批准号: 9004839
• 负责人: L.Nicholas Ornston
• 金额: $ 28.6万
• 依托单位: Yale University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-04-15 至 1994-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9004839&HistoricalAwards=false
• 关键词: Evolution; Intradiol; Dioxygenase; Genes; Bacteria

The research program is designed to explore how the properties of genes and the stability of regions within genes are influenced by neighboring DNA sequences. Bacterial intradiol dioxygenase genes, the subjects of the investigation, share common ancestry and have undergone numerous rearrangements during their evolutionary divergence. Rearrangements might be expected to lead to the physical separation of independently transcribed genes, but the chromosomal position of divergent oxygenase genes has been conserved within different supraoperonic clusters. Selective forces favoring the clustering of genes will be explored by examining the physiological and genetic consequences of directed transposition of oxygenase genes from one cluster to another. Transposition can lead to genetic instability, and a possible source of instability is sequence-directed mutation, a process that can lead to deletions between regions of DNA sequence repetition. The extent to which sequence-directed mutations occur will be explored by comparison of the DNA sequences of genes that have undergone spontaneous mutation either in their normal location or after transposition to a different cluster. Processes that lead to sequence-directed mutation also might contribute to genetic repair, and this possibility will be explored by analysis of DNA sequence of mutations that revert readily. Enzymatic activation of oxygen is a fundamental biological process, and the genetic analysis of oxygenases will increase our understanding of biochemical steps that direct the assimilation of molecular oxygen into organic substrates. We plan to isolate mutant oxygenases that are functional but altered in substrate specificity or in catalytic efficiency,. Analysis of these proteins is likely to provide novel insight into interactions between oxygenases and their substrates.

该研究计划旨在探索基因的特性和基因内区域的稳定性如何受到邻近DNA序列的影响。细菌内醇双加氧酶基因，研究的对象，具有共同的祖先，并在其进化分化过程中经历了多次重排。重排可能会导致独立转录基因的物理分离，但不同的加氧酶基因的染色体位置在不同的上操纵子簇中是保守的。通过检查加氧酶基因从一个簇到另一个簇的定向转位的生理和遗传后果，将探索有利于基因聚类的选择力。转位可能导致遗传不稳定，而不稳定的一个可能来源是序列定向突变，这一过程可能导致DNA序列重复区域之间的缺失。序列导向突变发生的程度将通过比较在其正常位置或转置到不同簇后发生自发突变的基因的DNA序列来探索。导致序列导向突变的过程也可能有助于基因修复，这种可能性将通过分析易于恢复的突变的DNA序列来探索。氧的酶活化是一个基本的生物过程，加氧酶的遗传分析将增加我们对指导分子氧同化到有机底物的生化步骤的理解。我们计划分离出功能性突变的加氧酶，但在底物特异性或催化效率上发生了变化。对这些蛋白质的分析可能为加氧酶及其底物之间的相互作用提供新的见解。