title: The proto-MHC of placozoans, a region specialized in cellular stress and ubiquitination/proteasome pathways.
abstract: The MHC is a large genetic region controlling Ag processing and recognition by T lymphocytes in vertebrates. Approximately 40% of its genes are implicated in innate or adaptive immunity. A putative proto-MHC exists in the chordate amphioxus and in the fruit fly, indicating that a core MHC region predated the emergence of the adaptive immune system in vertebrates. In this study, we identify a putative proto-MHC with archetypal markers in the most basal branch of Metazoans--the placozoan Trichoplax adhaerens, indicating that the proto-MHC is much older than previously believed--and present in the common ancestor of bilaterians (contains vertebrates) and placozoans. Our evidence for a T. adhaerens proto-MHC was based on macrosynteny and phylogenetic analyses revealing approximately one third of the multiple marker sets within the human MHC-related paralogy groups have unique counterparts in T. adhaerens, consistent with two successive whole genome duplications during early vertebrate evolution. A genetic ontologic analysis of the proto-MHC markers in T. adhaerens was consistent with its involvement in defense, showing proteins implicated in antiviral immunity, stress response, and ubiquitination/proteasome pathway. Proteasome genes psma, psmb, and psmd are present, whereas the typical markers of adaptive immunity, such as MHC class I and II, are absent. Our results suggest that the proto-MHC was involved in intracellular intrinsic immunity and provide insight into the primordial architecture and functional landscape of this region that later in evolution became associated with numerous genes critical for adaptive immunity in vertebrates.
authors.affiliation: Department of Gene Technology, Tallinn University of Technology, Tallinn 12618, Estonia;
authors.forename: Jaanus
authors.initials: J
authors.lastname: Suurväli
authors.affiliation: Institut National de la Recherche Agronomique, Virologie et Immunologie Moléculaires, F-78350 Jouy-en-Josas, France;
authors.forename: Luc
authors.initials: L
authors.lastname: Jouneau
authors.affiliation: Institut National de la Recherche Agronomique, Biologie du Développement et Reproduction, F-78350 Jouy-en-Josas, France;
authors.forename: Dominique
authors.initials: D
authors.lastname: Thépot
authors.affiliation: Institut de Mathématiques de Toulouse, Université Paul Sabatier, F-31000 Toulouse, France;
authors.forename: Simona
authors.initials: S
authors.lastname: Grusea
authors.affiliation: Université Aix Marseille, Centre National de la Recherche Scientifique, Centrale Marseille, F-13331 Marseille, France; and.
authors.forename: Pierre
authors.initials: P
authors.lastname: Pontarotti
authors.affiliation: Zoology and Evolutionary Biology Department, University of Basel, CH-4051 Basel, Switzerland pierre.boudinot@jouy.inra.fr sirje.boudinot@gmail.com.
authors.forename: Louis
authors.initials: L
authors.lastname: Du Pasquier
authors.affiliation: Department of Gene Technology, Tallinn University of Technology, Tallinn 12618, Estonia;
authors.forename: Sirje
authors.initials: S
authors.lastname: Rüütel Boudinot
authors.affiliation: Institut National de la Recherche Agronomique, Virologie et Immunologie Moléculaires, F-78350 Jouy-en-Josas, France; pierre.boudinot@jouy.inra.fr sirje.boudinot@gmail.com.
authors.forename: Pierre
authors.initials: P
authors.lastname: Boudinot
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics*; D000818:Animals; D005075:Biological Evolution; D016678:Genome; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics* / Q000276:immunology; D009414:Nerve Growth Factors / Q000235:genetics; D010802:Phylogeny; D054909:Placozoa / Q000235:genetics* / Q000276:immunology*; D046988:Proteasome Endopeptidase Complex / Q000235:genetics; D013312:Stress, Physiological / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology; D054875:Ubiquitination / Q000235:genetics
chemical_list: D009414:Nerve Growth Factors; D046988:Proteasome Endopeptidase Complex