A possible role of exon-shuffling in the evolution of signal peptides of human proteins

It was recently shown that there is a predominance of phase 1 introns near the cleavage site of signal peptides encoded by human genes. It was suggested that this biased distribution was due to intron insertion at AGmid R:G proto-splice sites. However, we found that there is no disproportional excess of AGmid R:G that would support insertion at proto-splice sites. In fact, all nGmid R:G sites are enriched in the vicinity of the cleavage site. Additional analyses support an alternative scenario in which exon-shuffling is largely responsible for such excess of phase 1 introns.