Alternative splicing: a missing piece in the puzzle of intron gain.

Spliceosomal introns, a hallmark of eukaryotic gene organization, were an unexpected discovery. After three decades, crucial issues such as when and how introns first appeared in evolution remain unsettled. An issue yet to be answered is how intron positions arise de novo. Phylogenetic investigations concur that intron positions continue to emerge, at least in some lineages. Yet genomic scans for the sources of introns occupying new positions have been fruitless. Two alternative solutions to this paradox are: (i) formation of new intron positions halted before the recent past and (ii) it continues to occur, but through processes different from those generally assumed. One process generally dismissed is intron sliding--the relocation of a preexisting intron over short distances--because of supposed associated deleterious effects. The puzzle of intron gain arises owing to a pervasive operational definition of introns, which sees them as precisely demarcated segments of the genome separated from the neighboring nonintronic DNA by unmovable limits. Intron homology is defined as position homology. Recent studies of pre-mRNA processing indicate that this assumption needs to be revised. We incorporate recent advances on the evolutionarily frequent process of alternative splicing, by which exons of primary transcripts are spliced in different patterns, into a new model of intron sliding that accounts for the diversity of intron positions. We posit that intron positional diversity is driven by two overlapping processes: (i) background process of continuous relocation of preexisting introns by sliding and (ii) spurts of extensive gain/loss of new intron sequences.