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- Exploiting Codon-Triplets Association for Genome Primary Structure AnalysisPublication . Lousado, José; Oliveira, José; Moura, Gabriela; Santos, ManuelAbstract— The way evolution shapes the arrangement of synonymous codons within open reading frames (ORF) for fine tuning mRNA decoding efficiency is not yet understood. Since the ribosome has 3 tRNA binding sites, the context of triplets should be relevant to decoding fidelity and efficiency. We have developed a software application for large-scale analysis of codon-triplet associations to shed new light into this problem. The developed algorithms identify codon-triplets context biases, allowing for large scale comparative codon-triplet analysis and for identification of alterations to the standard genetic code.
- Large scale comparative genomics of codon contextPublication . Lousado, José; Moura, Gabriela; Pinheiro, Miguel; Oliveira, José; Santos, ManuelThe efficiency of protein synthesis is highly dependent on codon usage and codon context. Indeed, the choice of particular synonymous codons is constrained by neighbour codons (codon context) to optimize mRNA decoding speed and accuracy. This is related to spatial (steric) effects created by the need to accommodate 3 tRNAs in the ribosome A-, P- and E-sites. Since these tRNAs interact with each other, with their cognate codons and with various structural domains of rRNAs, the structure of the 6 nucleotide RNA helix formed by the anticodon-codon interactions is strongly int1uenced by the type of codons and tRNAs present in the ribosome decoding centre. To ensure proper tRNA selection and correct codon decoding the rRNA monitors the structure of the codon-anticodon RNA helix. We hypothesized that large scale comparative analysis of 3 consecutive codons, corresponding to the ribosome A-, P- and E-sites codons, would unveil novel codon biases and "bad" codon combinations that are error prone. For this, we have built a software package that counts codon triplets in complete assemblies of open reading frames (ORFeomes) and used the ORFeome sequences of 12 fungal species, including Aspergillus fumigatus, Saccharomyces cerevisiae, and Candida albicans to validate our working hypothesis. We have used data mining methodologies to explore this large dataset of 220,000 combinations of 3 consecutive codons, and extracted the most biased contexts. The data showed that three-codon contexts are species-specific, although major context rules could also be found. Interestingly, biases introduced at DNA replication and transcription levels, namely trinucleotide repeats, play an important role in the evolution of ORFeomes. Candida albicans revealed unique features and very strong context biases. For example, codon triplet biases is much stronger in C. albicans than in other species and it has a very high number of consecutive codon repeats, which comprise up to 6% of the total ORFeome
- GeneSplit - Uma Aplicação para o Estudo de Associações de Codões e de Aminoácidos em ORFeomasPublication . Lousado, José; Oliveira, José; Moura, Gabriela; Santos, ManuelA descodificação de genomas, em particular do genoma humano, constituiu um marco cientifico extremamente importante nas últimas décadas e veio abrir caminho a novas áreas de investigação como a genómica e a proteómica. Espera-se que os avanços de conhecimento introduzidos por estas áreas tragam novas perspectivas sobre a forma como são diagnosticadas e tratadas muitas das doenças actuais, nomeadamente as que têm uma associação clara com disfunções ao nível do genotipo. Neste artigo, apresentamos uma aplicação computacional que permite estudar associações anormais de codões em orfeomas, i.e. em sequências responsáveis pela construção de proteínas. Os resultados biológicos já obtidos mostram claramente a utilidade prática do software desenvolvido, que é disponibilizado de uma forma pública para a comunidade científica