Biased codon usage near intron-exon junctions: selection on splicing enhancers, splice-site recognition or something else?

Two groups recently argued that, in human genes, synonymous sites near intron-exon junctions undergo selection for correct splicing. However, neither study controlled for the possibility of an underlying nucleotide bias at the ends of exons. In this article, we show that generalized A and T enrichment exists, which could be independent of splicing regulation. Evidence for selection between synonymous codons that are associated with splicing enhancers remains after controlling for this bias, whereas support for cryptic splice-site avoidance is diminished.