Fig. 2

Examples of ex nihilo motif gain and motif loss. a The N-terminus of the SHOC2 contains an S2- > G mutation in multiple Noonan-like syndrome patients that “knocks in” an N-myristoylation motif [26]. Blue bold residues signify the specificity determining residues of the motif. b A PxIxIT calcineurin-docking motif in S. cerevisiae Serine/threonine-protein kinase ELM1 (Elm1) has likely evolved in the common ancestor of S. cerevisiae and S. paradoxus [27]. c A human-centric phylogeny of E3 ubiquitin-protein ligase Mdm2 (Mdm2). An RxL Cyclin docking motif was gained in the rodent Mdm2 proteins as a result of a four amino acid deletion (grey region) [117]. Green bold residues signify the position of the residues corresponding to the specificity determining residues of the motif before the SDSI deletion. d Example of motif loss contributing to functional divergence post-duplication. S. cerevisiae ohnologues Ace2 and Swi5 were both retained after the whole genome duplication (WGD) but have functionally diverged post duplication, in part, by the loss of a serine/threonine-protein kinase Cbk1 docking site and two Cbk1 phosphosites in the Swi5 lineage. A representative example of a single pre-WGD homologue in Lachancea waltii shows the modular architecture of the Ace2/Swi5 ancestor [36]. e Example of motif gain contributing to functional divergence post-duplication. The Cyclin A and Cyclin B regulatory subunits of the CDK family protein kinases share a common ancestor that contained a D box motif to recruit the APC/C E3 ubiquitin ligase promoting Cyclin destruction during mitosis. Post-duplication the Cyclin A lineage gained an ABBA motif allowing Cyclin A to be destroyed earlier than Cyclin B during prometaphase [40]. f The accumulation of the Nx[TS] glycosylation motifs in hemagglutinin of Influenza H3N2 over the last 40 years. The number of glycosylation motifs has increased from two to seven tuning the trade-off between host receptor binding and immune evasion [118]