Intron Framing Exonic Nucleotides: A Compromise Between Protein Coding and Splicing Constraints

摘要

Introns in eukaryotic genes are located either between codons (phase 0) or within codons (phase 1 and 2).Phase 0 introns are more frequent. Several factors might contribute to this phenomenon with codon usage bias playing asignificant role. The nucleotides located at the very ends of intermediate exons are involved not only in protein coding butalso in splicing regulation. This study indicates that phase 0 introns create more flexibility for protein coding without affectingsplicing sensitive exonic nucleotides than the other two intron types. The canonic AG↓G site, for instance, is particularly frequent around phase 0 introns. In humans the observed frequency of AG↓G sites framing phase 0 introns is at least 2 to 3 times higher than in phase 1 and 2 introns. It is possible that the higher flexibility of exonic nucleotides surrounding phase 0 introns may serve as a driving force increasing frequencies of sites like AG↓G and this could lead to more stable or efficient splicing without compromising protein coding. If so, this type of selection might also contribute tohigher frequency of phase 0 introns.