Functional and Evolutionary Analyses Identify Proteolysis as a General Mechanism for NLRP1 Inflammasome Activation
(A) Results of PAML  and PARRIS  maximum likelihood analyses using 11 primate NLRP1 genes, providing evidence for positive selection for the entire NLRP1 gene, just the N-terminal linker region, or the entire ORF with the linker removed. The left two columns show two times the log likelihood difference and statistical support (p-value) comparing a model that allows (M8) or disallows (M7) positive selection in PAML. The right column shows the statistical support for a similar analysis in PARRIS. (B) Analyses of the N-terminal linker region of 20 primate NLRP1 genes reveal several codons have recurrently evolved under positive selection. An expanded view of the N-terminal linker region is shown, with hatched lines indicating regions that have lineage-specific insertions or deletions. Locations of individual codons that were identified by PAML  and FUBAR  maximum likelihood methods as evolving under positive selection are marked above the schematic. Locations of TEV sites introduced in this study are marked below the schematic. (C) Alignment of a portion of the linker region. At left is shown a phylogenetic tree of the analyzed species with hominoids in black text, Old World monkeys in green text and New World monkeys in blue text. Species marked with asterisks were also used for the analyses shown in panel (A). Amino acids marked in bold red differ from human NLRP1.