Miller, Steven W.Movsesyan, ArtemZhang, SuiFernández, RosaPosakony, James W.2020-03-192020-03-192019Miller SW, Movsesyan A, Zhang S, Fernández R, Posakony JW. Evolutionary emergence of Hairless as a novel component of the Notch signaling pathway. Elife. 2019; 8. pii: e48115. DOI: 10.7554/eLife.481152050-084Xhttp://hdl.handle.net/10230/43944Suppressor of Hairless [Su(H)], the transcription factor at the end of the Notch pathway in Drosophila, utilizes the Hairless protein to recruit two co-repressors, Groucho (Gro) and C-terminal Binding Protein (CtBP), indirectly. Hairless is present only in the Pancrustacea, raising the question of how Su(H) in other protostomes gains repressive function. We show that Su(H) from a wide array of arthropods, molluscs, and annelids includes motifs that directly bind Gro and CtBP; thus, direct co-repressor recruitment is ancestral in the protostomes. How did Hairless come to replace this ancestral paradigm? Our discovery of a protein (S-CAP) in Myriapods and Chelicerates that contains a motif similar to the Su(H)-binding domain in Hairless has revealed a likely evolutionary connection between Hairless and Metastasis-associated (MTA) protein, a component of the NuRD complex. Sequence comparison and widely conserved microsynteny suggest that S-CAP and Hairless arose from a tandem duplication of an ancestral MTA gene.application/pdfeng© 2019, Miller et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.info:eu-repo/semantics/articlehttp://dx.doi.org/10.7554/eLife.48115D. melanogasterCo-repressor recruitmentDevelopmental biologyDevelopmental system driftEvolutionary biologyEvolutionary noveltyMetastasis-associated proteinProtein evolutionSuppressor of Hairlessinfo:eu-repo/semantics/openAccess