title: Evolutionary and functional evidence for positive selection at the human CD5 immune receptor gene.
abstract: CD5 is a lymphocyte surface coreceptor of still incompletely understood function. Currently available information indicates that CD5 participates not only in cell-to-cell immune interactions through still poorly defined endogenous ligands expressed on hemopoietic and nonhemopoietic cells but also in recognition of exogenous and highly conserved microbial structures such as fungal β-glucans. Preceding single nucleotide polymorphism (SNP) data analysis provided evidence for a recent selective sweep in East Asia and suggested a nonsynonymous substitution at position 471 (A471V; rs2229177) of the cytoplasmatic region of the CD5 receptor as the most plausible target of selection. The present report further investigates the role of natural selection in the CD5 gene by a resequencing approach in 60 individuals representing populations from 3 different continents (20 Africans, 20 Europeans and 20 East Asians) and by functionally assaying the relevance of the A471V replacement on CD5 signaling. The high differentiation pattern found at the nonsynonymous A471V site together with the low diversity, most of the performed neutrality tests (Tajima's D, Fu and Li's F* and D*, and Fu's Fs) and the predominance of a major haplotype in East Asians strongly argue in favor of positive selection for the A471V site. Importantly, anti-CD5 monoclonal antibody cross-linking unveiled significant differences among A471V variants regarding the mitogen-activated protein kinase (MAPK) cascade activation on COS7 and on human peripheral blood mononuclear cells. Similar differences on MAPK activation and IL-8 cytokine release were also observed upon exposure of HEK293 cell transfectants expressing the A471V variants to Zymosan, a β-glucan-rich fungal particle. Taken together, the results provide evidence for the hypothesis of an adaptive role of the A471V substitution to environmental challenges, most likely infectious pathogens, in East Asian populations.
authors: Institut de Biologia Evolutiva (UPF-CSIC), Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Parc de Recerca Biomèdica de Barcelona, 08003 Barcelona, Spain. elena.bosch@upf.edu
authors: Elena
authors: E
authors: Carnero-Montoro
authors: Lizette
authors: L
authors: Bonet
authors: Johannes
authors: J
authors: Engelken
authors: Torsten
authors: T
authors: Bielig
authors: Mario
authors: M
authors: Martínez-Florensa
authors: Francisco
authors: F
authors: Lozano
authors: Elena
authors: E
authors: Bosch
mesh_terms: D000911:Antibodies, Monoclonal; D001483:Base Sequence; D018956:CD5 Antigens / Q000235:genetics* / Q000276:immunology; D002461:Cell Line, Transformed; D019143:Evolution, Molecular; D014644:Genetic Variation; D005838:Genotype; D057809:HEK293 Cells; D006239:Haplotypes; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000235:genetics*; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011971:Receptors, Immunologic / Q000235:genetics*; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D015054:Zymosan
chemical_list: D000911:Antibodies, Monoclonal; D018956:CD5 Antigens; D016209:Interleukin-8; D011971:Receptors, Immunologic; D015054:Zymosan; D020928:Mitogen-Activated Protein Kinases