P450 CODON USAGE

Todd D. Porter, Ph.D.

Amino acids are encoded by triplets of RNA (DNA in genes).  Because DNA and RNA are composed of 4 different nucleotides, there are 64 possible triplet combinations of these 4 nucleotides.  With only 20 amino acids, there is approximately a 3-fold excess of triplet combinations available to encode these amino acids. 

The table to the right shows the assignment of triplets (codons) to the 20 amino acids; this is know as the Standard Genetic Code.  In most organisms the codons for a given amino acid are not used equally; some triplets are used more frequently, while some triplets are only used rarely.  The pattern of usage differs, however, between different genes and between organisms.

This bias in codon usage has been attributed to a variety of selective evolutionary pressures, most notable of which is translational efficiency, the ability of the organism to synthesize the encoded protein.  Codon usage has been correlated with gene expression levels, tissue-specific patterns of expression, the degree of evolutionary conservation of proteins, and the overall or regional nucleotide composition of the genome.  Codon usage is least well understood in higher organisms.

These pages analyze codon usage for a large set of related genes, the cytochromes P450, in four mammalian species.  The P450 gene superfamily represents a compositionally homogeneous group of enzymes that exhibit a wide range of expression patterns and evolutionary relationships.  These characteristics, with its large size, make the P450 family attractive for a systematic analysis of codon usage.  Results demonstrate that codon usage in these genes corresponds most closely to local genomic composition, and reveal an unexpected force in the evolution of proteins.

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