title: The NBS-LRR architectures of plant R-proteins and metazoan NLRs evolved in independent events.
abstract: There are intriguing parallels between plants and animals, with respect to the structures of their innate immune receptors, that suggest universal principles of innate immunity. The cytosolic nucleotide binding site-leucine rich repeat (NBS-LRR) resistance proteins of plants (R-proteins) and the so-called NOD-like receptors of animals (NLRs) share a domain architecture that includes a STAND (signal transduction ATPases with numerous domains) family NTPase followed by a series of LRRs, suggesting inheritance from a common ancestor with that architecture. Focusing on the STAND NTPases of plant R-proteins, animal NLRs, and their homologs that represent the NB-ARC (nucleotide-binding adaptor shared by APAF-1, certain R gene products and CED-4) and NACHT (named for NAIP, CIIA, HET-E, and TEP1) subfamilies of the STAND NTPases, we analyzed the phylogenetic distribution of the NBS-LRR domain architecture, used maximum-likelihood methods to infer a phylogeny of the NTPase domains of R-proteins, and reconstructed the domain structure of the protein containing the common ancestor of the STAND NTPase domain of R-proteins and NLRs. Our analyses reject monophyly of plant R-proteins and NLRs and suggest that the protein containing the last common ancestor of the STAND NTPases of plant R-proteins and animal NLRs (and, by extension, all NB-ARC and NACHT domains) possessed a domain structure that included a STAND NTPase paired with a series of tetratricopeptide repeats. These analyses reject the hypothesis that the domain architecture of R-proteins and NLRs was inherited from a common ancestor and instead suggest the domain architecture evolved at least twice. It remains unclear whether the NBS-LRR architectures were innovations of plants and animals themselves or were acquired by one or both lineages through horizontal gene transfer.
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Urbach
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114; ausubel@molbio.mgh.harvard.edu.|Department of Genetics, Harvard Medical School, Boston, MA 02115.
authors.forename: Frederick M
authors.initials: FM
authors.lastname: Ausubel
mesh_terms: D000818:Animals; D005075:Biological Evolution; D060467:Disease Resistance / Q000235:genetics*; D019143:Evolution, Molecular; D007113:Immunity, Innate; D000090263:Leucine-Rich Repeat Proteins; D016013:Likelihood Functions; D008957:Models, Genetic; D005810:Multigene Family; D000070576:NLR Proteins / Q000737:chemistry / Q000235:genetics*; D043583:Nucleoside-Triphosphatase / Q000737:chemistry / Q000235:genetics*; D010802:Phylogeny; D010940:Plant Proteins / Q000737:chemistry / Q000235:genetics*; D000072417:Protein Domains; D011506:Proteins / Q000737:chemistry / Q000235:genetics*; D020449:Repetitive Sequences, Amino Acid; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013329:Structure-Activity Relationship; D000074436:Tetratricopeptide Repeat
chemical_list: D000090263:Leucine-Rich Repeat Proteins; D000070576:NLR Proteins; D010940:Plant Proteins; D011506:Proteins; D043583:Nucleoside-Triphosphatase
keywords: NLR; NOD-like receptors; R-protein; evolution; innate immunity