Can RNA selection pressure distort the measurement of Ka/Ks?

Recently, an interesting question has emerged in the evolutionary interpretation of sequence substitution data as evidence of amino acid selection pressure. Specifically, the Ka/Ks metric was designed to measure selection pressure on amino acid substitutions, assuming that the synonymous substitution rate Ks reflects the neutral nucleotide substitution rate. However, there is increasing evidence for selection pressure at silent sites due to constraints of RNA splicing. Is Ka/Ks an appropriate metric for selection pressure on amino acid substitutions, in the presence of other selection pressures acting only at the RNA level (such as selection for exonic splicing enhancers)? Or can the resulting decreases in Ks from such selection pressures introduce bias into the Ka/Ks metric, so that it no longer gives an accurate measure of amino acid level selection pressure? In this review, we present both mathematical models and empirical evidence for these divergent points of view.