Figure 7. Caspase-1 targets different gasdermins throughout evolution.
Phylogenetic tree indicating which GSDM caspase-1 cleaves in various clades of life. Branch lengths are not to scale. Coral, mollusks, hydras, and other invertebrates do not encode caspase-1 and cleave GSDMin with caspase-3. Coral and mollusks are indicated in this diagram. We did not identify any gasdermins in 3030 genomes from Ecdysozoa, the clade of which D. melanogaster and C. elegans are members. *Some teleost fish cleave GSDME with both caspase-1 and -3, however, other teleost fish, like the zebrafish, cleave GSDMEb with caspase-1 and GSDMEa with caspase-3, gasdermins that arose after a whole genome duplication event in teleost fish. Frogs and salamanders do not encode an identifiable GSDMA, but their GSDME contains prototypical caspase-3 cleavage sites. In mammals, GSDMD is cleaved by caspase-1 and GSDME by caspase-3. In caecilian amphibians—which are morphologically similar to snakes—birds, and reptiles, GSDMA is cleaved by caspase-1. We and others have confirmed that GSDME in birds is cleaved by caspase-3 (Figure 3J, Figure 3—figure supplement 2), and amphibian and reptile GSDME encodes prototypical caspase-3 cleavage sites.