Intron-dependent evolution: preferred types of exons and introns.

Exon insertions and exon duplications, two major mechanisms of exon shuffling, are shown to involve modules that have introns of the same phase class at both their 5'- and 3'-ends. At the sites of intronic recombinations exon insertions and duplications create new introns which belong to the same phase class as the recipient introns. As a consequence of repeated exon insertions and exon duplications introns of a single phase class predominate in the resulting genes, i.e. gene assembly by exon shuffling is reflected both by this nonrandom intron phase usage and by the correlation between the domain organization of the proteins and exon-intron organization of their genes. Genes that appeared before the eukaryote-prokaryote split do not show these diagnostic signs of exon shuffling. Since ancestral introns (e.g. self-splicing introns) did not favour intronic recombination, exon shuffling may not have been significant in the early part of protein evolution.