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Drosophila  Dscam1 (Down Syndrome Cell Adhesion Molecules) and vertebrate clustered protocadherins (Pcdhs) are two classic examples of the extraordinary isoform diversity from a single genomic locus.  Dscam1  encodes 38,016 distinct isoforms via mutually exclusive splicing in  D. melanogaster , while the vertebrate clustered  Pcdh s utilize alternative promoters to generate isoform diversity. Here we reveal a shortened  Dscam  gene family with tandemly arrayed 5′ cassettes in  Chelicerata . These cassette repeats generally comprise two or four exons, corresponding to variable Immunoglobulin 7 (Ig7) or Ig7–8 domains of  Drosophila  Dscam1. Furthermore, extraordinary isoform diversity has been generated through a combination of alternating promoter and alternative splicing. These  sDscams  have a high sequence similarity with  Drosophila Dscam1 , and share striking organizational resemblance to the 5′ variable regions of vertebrate clustered  Pcdh s. Hence, our findings have important implications for understanding the functional similarities between  Drosophila Dscam1  and vertebrate  Pcdh s, and may provide further mechanistic insights into the regulation of isoform diversity.

A large family of Dscam genes with tandemly arrayed 5′ cassettes in Chelicerata