COMIT: identification of noncoding motifs under selection in coding sequences

Coding nucleotide sequences contain myriad functions independent of their encoded protein sequences. We present the COMIT algorithm to detect functional noncoding motifs in coding regions using sequence conservation, explicitly separating nucleotide from amino acid effects. COMIT concurs with diverse experimental datasets, including splicing enhancers, silencers, replication motifs, and microRNA targets, and predicts many novel functional motifs. Intriguingly, COMIT scores are well-correlated to scores uncalibrated for amino acids, suggesting that nucleotide motifs often override peptide-level constraints.