Splicing and the Evolution of Proteins in Mammals regarding the dual role of exon sequences in encoding protein sequence and regulating splicing. A similar problem that also affects exons of edited genes where the coding sequence might also participate in RNA secondary structures that regulate editing.
http://biology.plosjournals.org/perlserv/?request=get-document&doi=10.1371%2Fjournal.pbio.0050014Author Summary:
While information for pre-mRNA splicing is largely within the intron sequences of genes, parts of the exons near the intron–exon boundary can, for example, function as splice enhancer elements. In principle, then, these parts of exons have two functions: to specify the amino acids of the resulting protein and to enable the correct removal of introns. What impact might this have on a gene's evolution? The authors show that near intron–exon boundaries, amino acid usage is biased towards nucleotides involved in splice control. Moreover, these parts of genes evolve especially slowly. They estimate that a gene with many exons would evolve at under half the rate of the same gene with no introns, simply owing to the need to specify where to remove introns. Likewise, genes that have lost their introns evolve especially fast near the former intron's location. Thus, human proteins may not be as optimised as they could be, as their sequence is serving two conflicting roles.
