Association of intron phases with conservation at splice site sequences and evolution of spliceosomal introns

How exon-intron structures of eukaryotic genes evolved under various evolut ionary forces remains unknown. The phases of spliceosomal introns (the plac ement of introns with respect to reading frame) provide an opportunity to a pproach this question. When a large number of nuclear introns in protein-co ding genes were analyzed, it was found that most introns were of phase 0, w hich keeps codons intact. We found that the phase distribution of spliceoso mal introns is strongly correlated with the sequence conservation of splice signals in exons; the relatively underrepresented phase 2 introns are asso ciated with the lowest conservation, the relatively overrepresented phase 0 introns display the highest conservation, and phase 1 introns are intermed iate. Given the detrimental effect of mutations in exon sequences near spli ce sites as found in molecular experiments, the underrepresentation of phas e 2 introns may be the result of deleterious-mutation-driven intron loss, s uggesting a possible genetic mechanism for the evolution of intron-exon str uctures.