The relationship between G+C-content and codon usage in genes of human, mus, rat, bovine and chicken nuclear genomes was investigated. Correlation and lineal regression analyses were carried out on plots that related the frequency of each codon within each synonymous codon group to the G+C-content of the coding sequence as a whole. Under GC pressure, in most of the quartet codon groups there is a preferential choice of the C-ending codon, except in leucine and valine codon groups where the choice of the G-ending codon is preferred. Among duets, the choice of codons specifying phenylalanine and glutamate shows the strongest dependence on G+C-content. The relationship found between G+C-content and codon usage in these genomes correlate with taxonomic distance.
INTRODUCTIONEarly works showed that the base ratio A+T/G+C of overall DNA differs among different species (1), and that different DNA segments isolated from organisms of a given species have the same base ratio (2,3).However, in vertebrates there are large differences in base composition between different DNA regions in the same genome. It has been shown recently (4), that the nuclear genome of warm-blooded vertebrates exhibits a compositional compartmentalization, being a mosaic of very long DNA sequences which are relatively homogeneous in their G+C-content (either G+C-rich or A+T-rich). These segments are named 'isochores', and it has been proposed that genes that map in chromosomal R-bands belong to G+C-rich isochores, and those in G-bands to A+T-rich isochores (4-8).According to the degeneracy of the genetic code one might expect that differences in G+C-content among genes could be accounted for by changes in G+C-content at the third, and to a lesser extent, at the first codon position, while the second codon position is constrained by the choice of amino acid. The G+C level found at each codon position in vertebrate genes shows a positive linear relationship to the G+C-content of the corresponding coding sequences; the slopes of the regression lines increase from second, to first, to third positions. Furthermore, a high correlation is found between the G + Ccontent at the third codon position of exons and the neighboring introns and flanking sequences. These relationships indicate the existence of compositional constraints operating on both coding and noncoding sequences (5-7,9,10).The variation in G + C-content through the genome is accompanied by changes in codon usage (4-7). In vertebrate genes, the G+C-content at the third codon position is distributed over a wide range (7), and subsequently, the codon-choice patterns of various genes in the same organism may differ considerably.