STATISTICAL-ANALYSIS OF VERTEBRATE SEQUENCES REVEALS THAT LONG GENES ARE SCARCE IN GC-RICH ISOCHORES

We compared the exon/intron organization of vertebrate genes belonging to different isochore classes, as predicted by their GC content at th ird codon position. Two main features have emerged from the analysis o f sequences published in GenBank: (1) genes coding for long proteins ( i.e., greater than or equal to 500 aa) are almost two times more frequ ent in GC-poor than in GC-rich isochores; (2) intervening sequences (= sum of introns) are on average three times longer in GC-poor than in G C-rich isochores. These patterns are observed among human, mouse, rat, cow, and even chicken genes and are therefore likely to be common to all warm-blooded vertebrates. Analysis of Xenopus sequences suggests t hat the same patterns exist in cold-blooded vertebrates. It could be a rgued that such results do not reflect the reality because sequence da tabases are not representative of entire genomes. However, analysis of biases in GenBank revealed that the observed discrepancies between GC -rich and GC-poor isochores are not artifactual, and are probably larg ely underestimated. We investigated the distribution of microsatellite s and interspersed repeats in introns of human and mouse genes from di fferent isochores. This analysis confirmed previous studies showing th at L1 repeats are almost absent from GC-rich isochores. Microsatellite s and SINES (Alu, B1, B2) are found at roughly equal frequencies in in trons from all isochore classes. Globally, the presence of repeated se quences does not account for the increased intron length in GC-poor is ochores. The relationships between gene structure and global genome or ganization and evolution are discussed.