Massive expansions of Dscam splicing diversity via staggered homologous recombination during arthropod evolution
- 24 November 2009
- journal article
- Published by Cold Spring Harbor Laboratory in RNA
- Vol. 16 (1), 91-105
- https://doi.org/10.1261/rna.1812710
Abstract
The arthropod Down syndrome cell adhesion molecule (Dscam) gene can generate tens of thousands of protein isoforms via combinatorial splicing of numerous alternative exons encoding immunoglobulin variable domains organized into three clusters referred to as the exon 4, 6, and 9 clusters. Dscam protein diversity is important for nervous system development and immune functions. We have performed extensive phylogenetic analyses of Dscam from 20 arthropods (each containing between 46 and 96 alternative exons) to reconstruct the detailed history of exon duplication and loss events that built this remarkable system over 450 million years of evolution. Whereas the structure of the exon 4 cluster is ancient, the exon 6 and 9 clusters have undergone massive, independent expansions in each insect lineage. An analysis of nearly 2000 duplicated exons enabled detailed reconstruction of the timing, location, and boundaries of these duplication events. These data clearly show that new Dscam exons have arisen continuously throughout arthropod evolution and that this process is still occurring in the exon 6 and 9 clusters. Recently duplicated regions display boundaries corresponding to a single exon and the adjacent intron. The boundaries, homology, location, clustering, and relative frequencies of these duplication events strongly suggest that staggered homologous recombination is the major mechanism by which new Dscam exons evolve. These data provide a remarkably detailed picture of how complex gene structure evolves and reveal the molecular mechanism behind this process.Keywords
This publication has 48 references indexed in Scilit:
- Alternative isoform regulation in human tissue transcriptomesNature, 2008
- A Double S Shape Provides the Structural Basis for the Extraordinary Binding Specificity of Dscam IsoformsCell, 2008
- Dscam diversity is essential for neuronal wiring and self-recognitionNature, 2007
- A Vast Repertoire of Dscam Binding Specificities Arises from Modular Interactions of Variable Ig DomainsCell, 2007
- Three-Dimensional Phylogeny Explorer: Distinguishing paralogs, lateral transfer, and violation of "molecular clock" assumption with 3D visualizationBMC Bioinformatics, 2007
- Global analysis of exon creation versus loss and the role of alternative splicing in 17 vertebrate genomesRNA, 2007
- Homophilic Dscam Interactions Control Complex Dendrite MorphogenesisNeuron, 2007
- AgDscam, a Hypervariable Immunoglobulin Domain-Containing Receptor of the Anopheles gambiae Innate Immune SystemPLoS Biology, 2006
- Gene Trees in Species TreesSystematic Biology, 1997
- CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choiceNucleic Acids Research, 1994