Funding entity: POCTI-32030/2001
Biologists have been wondering for many years how organisms evolved highly accurate information maintenance, transfer and decoding machineries. In particular, how the astonishing translational decoding rate of 20 codons per second is achieved with an average error of 10-4 to 10-5 per codon decoded, and how does the ribosome maintain the reading frame. The tools to answer these questions are not yet available but the row DNA sequencing data is. To shed new light into this important question, we have developed a software package that simulates ribosome scanning and reading during mRNA translation. The software screens fully or partially sequenced genomes and determines the arrangement of any particular codon in relation to the others by simultaneously fixing P-site codons and “memorizing” E and A-site codons during each translocation cycle. In doing so, it builds a genome wide codon context map that allows for identification of potential error prone mRNA sequences and gene expression regulatory points.
In this project, the various tools already developed will be integrated into a single software package to allow for automated search, downloading and editing of row DNA sequence data. Software tools for data display and new mathematical methodologies for identification of general rules governing mRNA translation will be developed. New tools for mapping mRNA regions of high decoding error and putative gene expression regulatory sequences present in the mRNAs, will also be developed. Finally, a database and an Internet Home Page will be built for making the data available to the scientific community. These in silico studies will be complemented with in vivo experiments. For this, a multidisciplinary team including two computing engineers, two mathematicians, one physicist, one biochemist and one molecular biologist has been assembled. To our knowledge this is the first Portuguese multidisciplinary team set up for functional genomics and the only one actively engaged on the development of software tools and mathematical models for genome analysis. It is expected that this project will provide important new insight on the role of the translational machinery on genome evolution.