New insights into the evolutionary dynamic and lineage divergence of gasdermin E in metazoa

• DOI: 10.3389/fcell.2022.952015
• Publication Date: 2022-07-22T15:50:55Z
• Authors: Zihao Yuan; Shuai Jiang; Kunpeng Qin; Li Sun
• Keywords: Tetrapod (structure); Lineage (genetic); Pyroptosis; Conserved sequence; Functional divergence

Gasdermin (GSDM) is a family of pore-forming proteins that induce pyroptosis. To date, the origin and evolution GSDM in Metazoa remain elusive. Here, we found emerged early Placozoa but absent large number invertebrates. In lower vertebrate, fish, three types GSDME, i.e., GSDMEa, GSDMEb, previously unreported type (designated GSDMEc), were idenitied. Evolutionarily, GSDMEs are distinctly separated: GSDMEa closely related to tetrapod GSDME; GSDMEb exists exclusively fish; GSDMEc forms lineage root GSDMA/B/C/D. shares conserved genomic features with probably prototype GSDMA, which existing all classes. displays fast evolutionary dynamics, likely as result transposition. A cross-metazoan analysis GSDME revealed caspase recognition motif tetrapods cnidarians, whereas has unique similar mammalian GSDMD, exhibits no apparent motif. Through functional test, four highly residues vertebrate proved be essential auto-inhibition. Together our results provide new insights into origin, evolution, function metazoan GSDMs.