title: Ancient origin of the new developmental superfamily DANGER.
abstract: Developmental proteins play a pivotal role in the origin of animal complexity and diversity. We report here the identification of a highly divergent developmental protein superfamily (DANGER), which originated before the emergence of animals (approximately 850 million years ago) and experienced major expansion-contraction events during metazoan evolution. Sequence analysis demonstrates that DANGER proteins diverged via multiple mechanisms, including amino acid substitution, intron gain and/or loss, and recombination. Divergence for DANGER proteins is substantially greater than for the prototypic member of the superfamily (Mab-21 family) and other developmental protein families (e.g., WNT proteins). DANGER proteins are widely expressed and display species-dependent tissue expression patterns, with many members having roles in development. DANGER1A, which regulates the inositol trisphosphate receptor, promotes the differentiation and outgrowth of neuronal processes. Regulation of development may be a universal function of DANGER family members. This family provides a model system to investigate how rapid protein divergence contributes to morphological complexity.
authors.affiliation: Biology Department, Pennsylvania State University, University Park, Pennsylvania, United States of America. nxn7@psu.edu
authors.forename: Nikolas
authors.initials: N
authors.lastname: Nikolaidis
authors.forename: Dimitra
authors.initials: D
authors.lastname: Chalkia
authors.forename: D Neil
authors.initials: DN
authors.lastname: Watkins
authors.forename: Roxanne K
authors.initials: RK
authors.lastname: Barrow
authors.forename: Solomon H
authors.initials: SH
authors.lastname: Snyder
authors.forename: Damian B
authors.initials: DB
authors.lastname: van Rossum
authors.forename: Randen L
authors.initials: RL
authors.lastname: Patterson
mesh_terms: D000465:Algorithms; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D019143:Evolution, Molecular; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D050437:Genes, Developmental / Q000235:genetics; D018398:Homeodomain Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics; D007448:Invertebrates / Q000235:genetics; D008565:Membrane Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics* / Q000502:physiology; D008957:Models, Genetic; D005810:Multigene Family; D020932:Nerve Growth Factor / Q000494:pharmacology; D016716:PC12 Cells / Q000187:drug effects; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D051381:Rats; D014714:Vertebrates / Q000235:genetics
chemical_list: D018398:Homeodomain Proteins; C516570:ITPRIP protein, human; C499231:MAB21L1 protein, human; D008565:Membrane Proteins; D020932:Nerve Growth Factor