RELATIONSHIP BETWEEN PROTO-SPLICE SITES AND INTRON PHASES - EVIDENCE FROM DICODON ANALYSIS

The coding sequence at the boundaries of exons flanking nuclear intron s shows some degree of conservation. To the extent that such sequences might be recognized by the splicing machinery, this conservation may be a derived result of evolution for efficient splicing. Alternatively , such conserved sequences might be remnants of proto-splice sites, wh ich might have existed early in eukaryotic genes and served as the tar gets for the insertion of introns, as has been proposed by the introns -late theory. The distribution of intron phases, the position of the i ntron within a codon, is biased with an over-representation of phase 0 introns. Could any distribution of proto-splice sites account for tod ay's intron phase distribution? Here, we examine the dicodon usage in six model organisms, based on current sequences in the GenBank databas e, and predict the phase distribution that would be expected if intron s had been inserted into proto-splice sites. However, these prediction s differ between the various model organisms and disagree with the obs erved intron phase distributions. Thus, we reject the hypothesis that introns are inserted into hypothetical proto-splice sites. Finally, we analyze the sequences around the splice sites of introns in all six o f the species to show that the actual conservation of sequence in exon regions near introns is very small and differs considerably between t hese species, which is inconsistent with a general proto-splice sites model.