A recent report in Science indicates that immune-receptor diversity is evolutionarily conserved as far back as insects: in the immunocompetent cells of insects, alternative splicing of the mRNA encoding immunoglobulin-superfamily receptor Down's syndrome cell-adhesion molecule (DSCAM) has the potential to generate more than 18,000 distinct protein isoforms.

The presence of highly diverse immune receptors generated by recombination-activating-gene-mediated somatic gene rearrangement is restricted to a subset of jawed vertebrates. However, it has previously been shown that the gene encoding Drosophila melanogaster DSCAM — which is essential for neuronal wiring — contains both constant and variable exons and that alternative splicing could allow for the generation of more than 19,000 distinct DSCAM extracellular domains. So, Watson et al. set out to analyse DSCAM expression in immunocompetent cells in D. melanogaster. It was shown that haemocytes and fat-body cells — cells of the insect immune system — expressed multiple Dscam mRNAs, most of which contained unique combinations of the variable exons, although some splice variants were more common than others. Consistent with this, proteins with amino-acid sequences corresponding to alternatively spliced mRNA transcripts were secreted by the haemocyte-like S2 cell line. Because soluble DSCAM proteins were also found in haemolymph serum, the authors suggest that thousands of DSCAM isoforms might circulate in the haemolymph of D. melanogaster.

An immune function for DSCAM isoforms was indicated by the observation that phagocytosis of heat-killed, fluorescently labelled Escherichia coli was impaired if haemocytes were isolated from D. melanogaster larvae expressing markedly reduced levels of DSCAM or if S2 cells were cultured for a short period in the presence of DSCAM-specific antibodies. Furthermore, two DSCAM isoforms were found to bind live E. coli, although a third did not. Binding was dependent on the ten amino-terminal domains, which include the region encoded by the three variable exons, indicating that exon usage might determine the binding properties of an individual DSCAM isoform.

Importantly, other insect species (Tribolium castaneum and Bombyx mori) also expressed alternatively spliced Dscam mRNAs, indicating that DSCAM diversity is conserved across insect species. These studies lead the authors to suggest that immune-receptor diversity in species as evolutionarily diverse as insects and jawed vertebrates is indicative of convergent evolution, although the altered splicing of Dscam mRNA provides a new mechanism by which immune-receptor diversity is generated.