An attempt to resolve this problem has been made, for example by focusing on synonymous substitutions in one reading frame which indeed are unconstrained in the other [18] . Hein & Støvlbaek [5] developed an evolutionary model particular to multiple coding regions, and used this for a study of selection on these. de Groot et al. [1] used this model of varying selection to comparatively annotate two viral genomes with evolved gene structure.