title: The evolving doublecortin (DCX) superfamily.
abstract: BACKGROUND
  Doublecortin (DCX) domains serve as protein-interaction platforms. Mutations in members of this protein superfamily are linked to several genetic diseases. Mutations in the human DCX gene result in abnormal neuronal migration, epilepsy, and mental retardation; mutations in RP1 are associated with a form of inherited blindness, and DCDC2 has been associated with dyslectic reading disabilities.
  
  
  RESULTS
  The DCX-repeat gene family is composed of eleven paralogs in human and in mouse. Its evolution was followed across vertebrates, invertebrates, and was traced to unicellular organisms, thus enabling following evolutionary additions and losses of genes or domains. The N-terminal and C-terminal DCX domains have undergone sub-specialization and divergence. Developmental in situ hybridization data for nine genes was generated. In addition, a novel co-expression analysis for most human and mouse DCX superfamily-genes was performed using high-throughput expression data extracted from Unigene. We performed an in-depth study of a complete gene superfamily using several complimentary methods.
  
  
  CONCLUSIONS
  This study reveals the existence and conservation of multiple members of the DCX superfamily in different species. Sequence analysis combined with expression analysis is likely to be a useful tool to predict correlations between human disease and mouse models. The sub-specialization of some members due to restricted expression patterns and sequence divergence may explain the successful addition of genes to this family throughout evolution.
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel. orly.reiner@weizmann.ac.il
authors.forename: Orly
authors.initials: O
authors.lastname: Reiner
authors.forename: Frédéric M
authors.initials: FM
authors.lastname: Coquelle
authors.forename: Bastian
authors.initials: B
authors.lastname: Peter
authors.forename: Talia
authors.initials: T
authors.lastname: Levy
authors.forename: Anna
authors.initials: A
authors.lastname: Kaplan
authors.forename: Tamar
authors.initials: T
authors.lastname: Sapir
authors.forename: Irit
authors.initials: I
authors.lastname: Orr
authors.forename: Naama
authors.initials: N
authors.lastname: Barkai
authors.forename: Gregor
authors.initials: G
authors.lastname: Eichele
authors.forename: Sven
authors.initials: S
authors.lastname: Bergmann
mesh_terms: D000818:Animals; D002417:Cattle; D002645:Chickens / Q000235:genetics; D016000:Cluster Analysis; D004285:Dogs; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D019143:Evolution, Molecular; D020869:Gene Expression Profiling; D005800:Genes, Fungal; D017343:Genes, Plant; D006801:Humans; D017403:In Situ Hybridization; D008253:Macaca mulatta / Q000235:genetics; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008957:Models, Genetic; D005810:Multigene Family; D009479:Neuropeptides / Q000235:genetics*; D009893:Opossums / Q000235:genetics; D002679:Pan troglodytes / Q000235:genetics; D010802:Phylogeny; D017434:Protein Structure, Tertiary / Q000235:genetics; D051381:Rats; D012689:Sequence Homology, Nucleic Acid
chemical_list: C000714328:DCX protein, human; C000714847:Dcx protein, mouse; C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides