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The evolving doublecortin (DCX) superfamily

Orly Reiner1*, Frédéric M Coquelle15, Bastian Peter2, Talia Levy1, Anna Kaplan1, Tamar Sapir1, Irit Orr3, Naama Barkai1, Gregor Eichele4 and Sven Bergmann12

Author Affiliations

1 Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel

2 Department of Medical Genetics, University of Lausanne, Switzerland

3 Department of Biological Services, Weizmann Institute of Science, Rehovot, Israel

4 Max-Planck Institute, Hannover, Germany

5 CNRS – UMR 6026, Université de Rennes 1, Equipe SDM, Campus de Beaulieu – Bât. 13, 35042 Rennes cedex, France

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BMC Genomics 2006, 7:188  doi:10.1186/1471-2164-7-188

Published: 26 July 2006



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.


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.


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.