Different Evolutionary Strategies for the Origin of Caspase-1 Inhibitors

Caspase 1 (CASP-1) inhibitors share sequence similarity to CASP-1 itself and are all mapped to chr11q22.3. Here we show that these inhibitors are all products of a series of gene duplications that occurred at this locus after the divergence between human and mouse. Surprisingly, stop codons originated independently in all duplicated copies to generate CARD-only proteins with inhibitory activity. We discuss this evolutionary model in the context of both neo- and subfunctionalization.