ARCHITECTURAL LIMITS ON SPLIT GENES

Exon/intron architecture varies across the eukaryotic kingdom with lar ge introns and small exons the rule in vertebrates and the opposite in lower eukaryotes. To investigate the relationship between exon and in tron size in pre-mRNA processing, internally expanded exons were place d in vertebrate genes with small and large introns, Both exon and intr on size influenced splicing phenotype, Intron size dictated if large e xons were efficiently recognized, When introns were large, large exons were skipped; when introns were small, the same large exons were incl uded, Thus, large exons were incompatible for splicing if and only if they were flanked by large introns. Both intron and exon size became p roblematic at approximate to 500 nt, although both exon and intron seq uence influenced the size at which exons and introns failed to be reco gnized, These results indicate that present-day gene architecture refl ects at least in part limitations on exon recognition, Furthermore, th ese results strengthen models that invoke pairing of splice sites duri ng recognition of pre-mRNAs, and suggest that vertebrate consensus seq uences support pairing across either introns or exons.