STRONG CONSERVATION OF NONCODING SEQUENCES DURING VERTEBRATES EVOLUTION - POTENTIAL INVOLVEMENT IN POSTTRANSCRIPTIONAL REGULATION OF GENE-EXPRESSION

Comparison of nucleotide sequences from different classes of vertebrat es that diverged more than 300 million years ago, revealed the existen ce of highly conserved regions (HCRs) with more than 70% similarity ov er 100 to 1450 nt in non-coding parts of genes. Such a conservation is unexpected because it is much longer and stronger than what is necess ary for specifying the binding of a regulatory protein. HCRs are relat ively frequent, particularly in genes that are essential to cell life. In multigene families, conserved regions are specific of each isotype and are probably involved in the control of their specific pattern of expression. Studying HCRs distribution within genes showed that funct ional constraints are generally much stronger in 3'-non-coding regions than in promoters or introns. The 3'-HCRs are particularly A + T-rich and are always located in the transcribed untranslated regions of gen es, which suggests.that they are involved in post-transcriptional proc esses. However, current knowledge of mechanisms that regulate mRNA exp ort, localisation, translation, or degradation is not sufficient-to ex plain the strong functional constraints that we have characterised.