Origin and Evolution of Dishevelled

Dishevelled (Dsh or Dvl) is an important signaling protein, playing a key role in Wnt signaling and relaying cellular information for several developmental pathways. Dsh is highly conserved among metazoans and has expanded into a multigene family in most bilaterian lineages, including vertebrates, planarians, and nematodes. These orthologs, where explored, are known to have considerable overlap in function, but evidence for functional specialization continues to mount. We performed a comparative analysis of Dsh across animals to explore protein architecture and identify conserved and divergent features that could provide insight into functional specialization with an emphasis on invertebrates, especially nematodes. We find evidence of dynamic evolution of Dsh, particularly among nematodes, with taxa varying in ortholog number from one to three. We identify a new domain specific to some nematode lineages and find an unexpected nuclear localization signal conserved in many Dsh orthologs. Our findings raise questions of protein evolution in general and provide clues as to how animals have dealt with the complex intricacies of having a protein, such as Dsh, act as a central messenger hub connected to many different and vitally important pathways. We discuss our findings in the context of functional specialization and bring many testable hypotheses to light.