Analysis of tRNA gene evolution in bacterial genomes

转运RNA（transfer RNA，tRNA）基因是最重要的基因之一。大量的研究涉及tRNA序列鉴定、结构预测和同一性元件。然而，人们对tRNA基因在全基因组范围内的数量、组织和功能特异性方面的进化知之甚少。更好地理解tRNA库的进化有望揭示与蛋白质表达相关的许多重要问题，例如tRNA拷贝数与蛋白质合成之间的联系，遗传密码的进化和tRNA功能转变。此外，由于tRNA基因分散在整个基因组中，它们代表了一个有趣的基因子集，用于研究改变基因组的主要进化事件。* 最近，我们推断了50个芽孢杆菌菌株中tRNA基因的进化历史。我们观察到芽孢杆菌基因组中的tRNA基因主要受到复制和缺失的影响。我们还观察到复制轴（起点或终点）周围发生大的倒位。最有趣和令人惊讶的结果来自于芽孢杆菌和大肠杆菌中不同类型事件发生率的比较。杆菌在芽孢杆菌中推断的平均重复率比在大肠杆菌中报道的低24倍。大肠杆菌的研究，而损失和转化的平均率都低12倍。这些比率非常低，表明芽孢杆菌中作用于tRNA基因库的强选择压力。* 我的研究计划的目标是在其他细菌中进行类似的分析。随着越来越多的细菌基因组被完全测序，有越来越多的有趣的细菌属进行分析：例如李斯特菌，沙门氏菌，葡萄球菌，链球菌和弧菌。将这些属的进化与芽孢杆菌属和大肠杆菌属的进化进行比较。对大肠杆菌的研究将有助于了解某些属在tRNA基因的数量和组织方面是否明显比其他属更稳定，以及这种稳定性与这些不同细菌的生活环境之间是否存在相关性。然而，由于这些新测序的细菌属中的大多数与芽孢杆菌属相比表现出非常高的分歧水平，因此需要开发新的算法方法来推断这些基因组中tRNA基因的进化历史。特别是，考虑重叠事件的方法和考虑序列、基因组背景和结构信息的方法将被开发用于两个基因组的比较，然后将被优化和推广以计算整个同源性背景下的最小进化距离。拟议的研究计划将为高素质的人员提供一个双学科的培训环境，重点是开发高效的算法和分析生物数据。

Transfer RNA (tRNA) genes are among the most important and ancient genes. A large number of studies have addressed tRNA sequence identification, structure prediction and identity elements. However, little is known about the evolution of tRNA genes in terms of number, organization and functional specificity on a genome-wide scale. Having a better understanding of tRNA repertoire evolution is expected to shed light on many important questions related to protein expression, such as the link between tRNA copy number and protein synthesis, the evolution of the genetic code and tRNA functional shift. Moreover, since tRNA genes are dispersed throughout the genome, they represent an interesting subset of genes to study the major evolutionary events that have transformed the genomes. ***Recently, we inferred the evolutionary history of the tRNA genes in 50 Bacillus strains. We observed that the tRNA genes in Bacillus genomes are mostly affected by duplications and deletions. We also observed large inversions occurring around the axes of replication (origin or terminus). The most interesting and surprising result came from the comparison of the rates of the different types of events in Bacillus and E. coli. The average rate of duplications inferred in Bacillus was 24 times lower than the one that was reported in the E. coli study, while the average rates of losses and inversions were both 12 times lower. These rates were extremely low, suggesting a strong selective pressure acting on tRNA gene repertoires in Bacillus. ***The goal of my research program is to conduct similar analyses in other bacteria. With the ever-increasing number of bacterial genomes being completely sequenced, there are more and more interesting bacterial genera to analyze: Listeria, Salmonella, Staphylococcus, Streptococcus and Vibrio for example. Comparing the evolution of those other genera with what was inferred in Bacillus and E. coli would help understand if certain genera are clearly more stable than others in terms of the number and the organization of tRNA genes, and if there is a correlation between this stability and the living environment of those different bacteria. However, as most of these newly sequenced bacterial genera exhibit a very high level of divergence compared to Bacillus, new algorithmic methods need to be developed to infer evolutionary histories of tRNA genes in those genomes. In particular, methods taking into account overlapping events and methods considering sequence, genomic context and structural information will be developed for the comparison of two genomes, then will be optimized and generalized to calculate the minimum evolutionary distance in the context of a whole phylogeny.***The proposed research program will provide a bi-disciplinary training environment for highly qualified personnel that focuses both on the development of efficient algorithms and the analysis of biological data.**