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We have hybridized the vertebrate telomeric sequence (TTAGGG)n on DNA compositional fractions from 13 mammalian species and 3 avian species, representing 9 and 3 orders, respectively. Our results indicate that the 50- to 100-kb fragments derived from telomeric regions are composed of GC-rich and GC-richest isochores. Previous works from our laboratory demonstrated that single-copy sequences from the human H3 isochore family (the GC-richest and gene-richest isochore in the human genome) share homology with compositionally correlated compartments of warm-blooded vertebrates. This correlation suggested that the GC-richest isochores are, as in the human genome, the gene-richest regions of warm-blooded vertebrates' genome. Moreover, this evidence suggests that telomeric regions are the most gene-dense region of all warm-blooded vertebrates. The implications of these findings are discussed.

All 69 homologous coding sequences that are currently available in four mammalian orders were aligned and the synonymous (ie., third) positions of quartet (fourfold degenerate) codons were divided into three classes (that will be called conserved, intermediate, and variable), according to whether they show no change, one change, and more than one change, respectively. The three classes were analyzed in their compositional patterns. In the majority of GC-rich genes, the three classes of positions (but especially conserved positions) exhibited significantly different base compositions compared to expectations based on a "random" substitution process from the "ancestral" (consensus) sequence to the present-day (actual) sequences. Significant differences were rare in GC-poor genes. An analysis of the present results indicates that natural selection plays a role in the synonymous nucleotide substitution process, especially in GC-rich genes which represent the vast majority of mammalian genes.

All 69 homologous coding sequences that are currently available in four mammalian orders were aligned and the synonymous positions of quartet and duet (fourfold and twofold degenerate) codons were divided into three classes (that will be called conserved, intermediate, and variable) according to whether they show no change, one change, or more than one change, respectively. We observed (1) that the frequencies of conserved, intermediate, and variable positions of quartet and duet codons are different in different genes; (2) that the frequencies of the three classes are significantly different from expectations based on a random substitution process in the majority of genes (especially for GC-rich genes) for quartet codons and in a minority of genes for doublet codons; and (3) that the frequencies of the three classes of positions of quartet codons are correlated with those of duet codons, the conserved positions of quartet and duet codons being, in addition, correlated with the degree of amino acid conservation. Our main conclusions are that synonymous substitution frequencies: (1) are gene-specific; (2) are not simply the result of a stochastic process in which nucleotide substitutions accumulate at random, over time; and (3) are correlated in quartet and duet codons.

As the correlations between GC levels in third codon positions (GC3) and intergenic sequence GC levels can be used to assess the distribution of genes in the human genome, they were studied in detail. Previous work from our laboratory has demonstrated the existence of linear correlations between GC levels of exons, introns, third codon positions, 5' flanking regions of genes, and long genomic DNA sequences (> or = 10 kb) or DNA molecules (50-100 kb) in which the genes are embedded. The present study confirms and extends the previous results using a larger set of data. Furthermore, an analysis of 4270 human genomic DNA and cDNA sequences has allowed us to confirm a correlation of GC3 against GC1+2. Recent additions to the sequence database have also allowed separate analyses of the 5' flanking regions of CpG island and non-CpG island genes as well as analyses of 3' flanking regions, which suggest that the GC levels of 3' flanking regions are closer to those of intergenic DNA than are those of other regions of genes.

We have hybridized a human DNA fraction corresponding to the GC-richest and gene-richest isochore family, H3, on compositional fractions of DNAs from 12 mammalian species and three avian species, representing eight and three orders, respectively. Under conditions in which repetitive sequences are competed out, the H3 isochore probe only or predominantly hybridized on the GC-richest fractions of main-band DNA from all the species investigated. These results indicate that single-copy sequences from the human H3 isochores share homology with sequences located in the compositionally corresponding compartments of the vertebrate genomes tested. These sequences are likely to be essentially formed by conserved coding sequences. The present results add to other lines of evidence indicating that isochore patterns are highly conserved in warm-blooded vertebrate genomes. Moreover, they refine recent reports (Sabeur et al., 1993; Kadi et al., 1993), and correct them in some details and also in demonstrating that the shrew genome does not exhibit the general mammalian pattern, but a special pattern.

Bony fishes (Osteichthyes) comprise over 22,000 species, about half of all vertebrate species. In order to investigate the phylogenetic relationships within this vertebrate class, we have studied the only protein whose primary structure is known in a rather large (27) number of fish species belonging to seven orders--the growth hormone. The phylogeny obtained using the maximum parsimony method based on amino acid sequences represents the first molecular phylogeny of teleostean fishes based on an extensive set of data. This phylogeny agrees remarkably well with the generally accepted phylogeny based on morphological characters and paleontological data.