Gene gain and loss in bacterial genomes and the dynamics of ribosomes
Gene gain and loss in bacterial genomes and the dynamics of ribosomes
批准号:
261831-2012
负责人:
Higgs, Paul
金额:
$2.48万
依托单位:
依托单位国家:
加拿大
项目类别:
Discovery Grants Program - Individual
财政年份:
2012
资助国家:
加拿大
项目状态:
已结题
起止时间:
2012-01-01 至 2013-12-31
中文摘要
虽然我们现在知道许多生物的完整基因组序列,但我们不知道许多基因的功能,我们对基因的获得和丢失的方式知之甚少。在细菌中,我们发现,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,而且每个基因组都包含其他基因组中不存在的独特基因。例如,某些基因的存在与否可以决定无害细菌和导致食物中毒的细菌之间的差异,或者它可以解释为什么一种菌株对抗生素有抗药性,而另一种菌株对抗生素敏感。更广泛地说,吸收新基因可能会让细胞改变它们的生活方式,并在新的生态位上定居。我们将对基因组中存在和缺失基因的分布进行计算研究。基因要么通过细胞内的变化获得,要么通过从细胞外插入“外来”基因获得——这一过程被称为水平基因转移。水平迁移挑战了通常将进化描述为分支树的说法。我们的目标是估计水平转移的速率,并了解树形图在多大程度上符合现代基因组数据。细胞内蛋白质合成的过程被称为翻译。蛋白质合成对细胞至关重要,因此我们期望翻译过程被进化选择,以在有限的资源下有效地产生蛋白质。核糖体是负责翻译的分子复合物。核糖体沿着信使rna一个接一个地移动,就像轨道上的火车一样。我们预计在翻译过程中可能会出现瓶颈,导致核糖体的交通堵塞。我们将开发翻译的计算机模拟和数学理论,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操作方式。我们的工作使用生物物理学的思想,并将它们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,这些技能在加拿大很受欢迎。
英文摘要
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.
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