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Effect of A+T% on Codon Usage and Amino Acid Selection in Poxvirus Genes.

Chris Upton

School of Life Sciences & Bioinformatics Center, JawaharLal Nehru University, New Delhi 110 067, India

Biochemistry & Microbiology, University of Victoria, British Columbia, Canada.

Poxviral genomes consist of a single linear double-stranded DNA molecule (150 - 320kb) capable of encoding more than 200 proteins. Many of these are not required for virus replication in vitro but contribute to fitness of the viruses in their natural animal hosts. Some of these proteins modulate the immune response and are of interest because they shed light on the processes of the host anti-viral response (e.g. proteins related to the host cytokine receptors for tumor necrosis factor, interferon-gamma and interleukin-1). It is apparent that the genes encoding these and many other poxviral proteins have been acquired from the host and subsequently modified within the poxvirus genome under the selective pressures imposed on these viruses.

The function of a significant number of poxvirus proteins remains to be identified. Recognition of relationships between poxvirus proteins and their eukaryotic counterparts is often difficult due to the low similarity and a requirement for the introduction of a relatively high number of gaps to produce optimal alignments. Although significant improvements to BLAST and FASTA have been made recently, as noted by the ability to match the poxvirus interferon gamma binding protein and uracil DNA glycosylase, we are particularly interested in enhancing the sensitivity of database searches for poxvirus homologs.

Data will be presented on our recent identification and characterization of several novel human cDNA's that encode proteins 45-50% identical to orthopoxvirus proteins. Since orthopoxvirus genomes are approximately 65% A+T, and the human cDNA&rsquos are approximately 35% A+T there is a considerable difference in codon usage between these genes. In addition, this difference in nucleotide composition has a significant influence on amino acid composition of the proteins. For example, the isoleucine:leucine ratio is greatly increased and the number proline and alanine residues (encoded by GC rich codons) is reduced significantly in the orthopoxvirus proteins. We are interested in the possibility of using this information to develop poxvirus specific scoring matrices for database searching.

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