Gene gain and loss in bacterial genomes and the dynamics of ribosomes

虽然我们现在知道了许多生物体的完整基因组序列，但我们不知道许多基因的功能，我们对基因获得和丢失的方式了解甚少。在细菌中，人们发现，即使我们观察同一物种的不同菌株，它们也只共享一小部分基因，每个基因组都包含其他基因组中不存在的独特基因。例如，某些基因的存在或缺失可以区分无害细菌和导致食物中毒的细菌，或者可以解释为什么一种菌株对抗生素有抗性，而另一种菌株对抗生素敏感。更广泛地说，新基因的吸收可能会使细胞改变它们的生活方式并殖民新的生态位。我们将对基因组中存在和不存在基因的分布进行计算研究。基因的获得要么是通过细胞内的变化，要么是通过从细胞外插入“外来”基因--这一过程被称为水平基因转移。水平转移挑战了通常将进化描述为分支树的观点。我们的目标是估计水平转移的速率，并了解树图在多大程度上支持现代基因组数据。细胞内蛋白质合成的过程称为翻译。蛋白质合成对细胞至关重要，因此我们希望翻译过程能够通过进化来选择，以有限的资源有效地生产蛋白质。核糖体是负责翻译的分子复合物。核糖体沿着信使RNA一个接一个地沿着移动，就像轨道上的火车。我们预计翻译过程中可能存在瓶颈，导致核糖体交通堵塞。我们将开发计算机模拟和翻译的数学理论，可用于解释不同基因表达水平的实验数据，以及自然选择对其基因序列的作用方式。我们的工作使用了生物物理学的思想，并将其与基因组学和微生物学的观察联系起来。学员将获得生物信息学，基因组分析，统计方法和软件开发方面的技能，这些技能在加拿大受到追捧。

Although we now know the complete genome sequence of many organisms, we do not know the function of many genes and we have a poor understanding of the way genes are gained and lost. In bacteria, it is found that even when we look at different strains of the same species, they only share a fraction of their genes, and each genome contains unique genes not present in the others. For example, the presence or absence of certain genes can make the difference between a harmless bacterium and one that causes food poisoning, or it can explain why one strain is resistant to antibiotics but another is susceptible. More broadly, uptake of new genes may allow cells to change their lifestyle and colonize new niches. We will carry out a computational study of the distribution of presence and absence of genes across genomes. Genes are gained either by changes inside the cell or by insertion of 'foreign' genes from outside the cell - a process known as horizontal gene transfer. Horizontal transfer challenges the usual representation of evolution as a branching tree. We aim to estimate the rate of horizontal transfer and to understand to what extent the tree picture holds up to modern genomic data. The process of protein synthesis inside a cell is known as translation. Protein synthesis is vital to a cell, so we expect the translation process to be selected by evolution to efficiently produce proteins with limited resources. Ribosomes are the molecular complexes that are responsible for translation. Ribosomes move along messenger RNAs one after another like trains on a track. We expect there may be bottlenecks in translation that cause traffic jams of ribosomes to build up. We will develop computer simulations and mathematical theories of translation that can be used to interpret experimental data on the levels of expression of different genes and the way that natural selection operates on their gene sequences. Our work uses ideas from biophysics and links them to observations in genomics and microbiology. Trainees will gain skills in bioinformatics, genome analysis, statistical methods and software development that are sought after in Canada.