The organization and evolution of the Dipteran and Hymenopteran Down syndrome cell adhesion molecule (Dscam) genes

BRENTON R. GRAVELEY; AMARDEEP KAUR; DORIAN GUNNING; S. LAWRENCE ZIPURSKY; LEE ROWEN; JAMES C. CLEMENS

doi:10.1261/rna.7105504

The organization and evolution of the Dipteran and Hymenopteran Down syndrome cell adhesion molecule (Dscam) genes

¹Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, Connecticut 06030-3301, USA
²Institute of System Biology, Seattle, Washington 98103, USA
³Department of Biological Chemistry, Howard Hughes Medical Institute, The David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California 90095, USA

Abstract

The Drosophila melanogaster Down syndrome cell adhesion molecule (Dscam) gene encodes an axon guidance receptor and can generate 38,016 different isoforms via the alternative splicing of 95 variable exons. Dscam contains 10 immunoglobulin (Ig), six Fibronectin type III, a transmembrane (TM), and cytoplasmic domains. The different Dscam isoforms vary in the amino acid sequence of three of the Ig domains and the TM domain. Here, we have compared the organization of the Dscam gene from three members of the Drosophila subgenus (D. melanogaster, D. pseudoobscura, and D. virilis), the mosquito Anopheles gambiae, and the honeybee Apis mellifera. Each of these organisms contains numerous alternative exons and can potentially synthesize tens of thousands of isoforms. Interestingly, most of the alternative exons in one species are more similar to one another than to the corresponding alternative exons in the other species. These observations provide strong evidence that many of the alternative exons have arisen by reiterative exon duplication and deletion events. In addition, these findings suggest that the expression of a large Dscam repertoire is more important for the development and function of the insect nervous system than the actual sequence of each isoform.

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