The evolving doublecortin (DCX) superfamily.
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.
Reiner
Orly
O
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel. orly.reiner@weizmann.ac.il
Coquelle
Frédéric M
FM
Peter
Bastian
B
Levy
Talia
T
Kaplan
Anna
A
Sapir
Tamar
T
Orr
Irit
I
Barkai
Naama
N
Eichele
Gregor
G
Bergmann
Sven
S
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
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