Codon usage adaptation in prokaryotic genomes

Identifier:  TDX:444

Handle: https://hdl.handle.net/20.500.11797/TDX444

Authors:  Puigbó Avalos, Pedro

Abstract:
This thesis is based in codon usage adaptation in prokaryotic genomes, especially the codon usage adaptation to a high expression. In genomes under translational selection, the group of highly expressed genes has a codon usage adapted to the most abundant tRNA species. We have developed a new iterative algorithm which predicts a group of highly expressed genes in genomes under translational selection by using the Codon Adaptation Index and the group of ribosomal protein genes as a seed. We have developed a new genomic database, called HEG-DB, to store genes that are predicted as highly expressed in prokaryotic complete genomes under strong translational selection. The database is freely available at http://genomes.urv.cat/HEG-DB and it has been published in Nucleic Acids Research. The predicted highly expressed genes are used as an initial filter to reduce the number of false positives of the Horizontal Gene Transfer Database, due to highly expressed genes are usually false positive in predictions of acquired genes. We have developed a new web sever, called OPTIMIZER (http://genomes.urv.cat/OPTIMIZER), which has been published in Nucleic Acids Research, to optimize the codon usage of DNA or RNA sequences. This new web server can be used to predict and optimize the level expression of a gene in heterologous gene expression or to express new genes that confer new metabolic capabilities in a given species. We have also analyzed an especial case of codon usage adaptation, which is called 'amelioration'. The 'amelioration' is the adaptation of foreign genes to a new genome. This is the case of mitochondrial genes encoded in the human nuclear genome and originally encoded in the proto-mitochondria. To test the 'amelioration' process we have developed an expected value of CAI (eCAI) to find out whether the differences in the CAI are statistically significant or whether they are the product of biased nucleotide and/or amino acid composition and a new bioinformatics tool called CAIcal (http://genomes.urv.cat/CAIcal). We have also analyzed the evolution of thermophilic adaptation in prokaryotes and we suggest that the amino acid composition signature in thermophilic organisms is a consequence of or an adaptation to living at high temperatures, not its cause. Our findings suggest that there have been several cases where the capacity for thermophilic adaptation has been gained or lost throughout the evolution of prokaryotes. These results have been published in Trends in Genetics. During my thesis I have worked for four months in the Bioinformatics Laboratory of the Biology Department at the National University of Ireland under the supervision of Dr James O. McInerney where I developed a new software program to compare phylogenetic trees called TOPD/FMTS (http://genomes.urv.cat/topd), that has been published in Bioinformatics.