title: Transposon-mediated death of an ancestral A-23-like allele: evolution of TCR-positioning motifs in the HLA-A lineage.
abstract: HLA-A alleles are characterized by tandem arginine and histidine/arginine motifs (i.e., R65 and H151R motifs) present on the α1- and α2-helix, respectively. In crystallographic structures, α/β T-cell receptors (TCR) contact both motifs and appear to be geometrically positioned for alloreactivity. Herein, bioinformatics of "dual-motif" MHC A-like alleles were investigated across phylogeny. While A-like alleles with the R65 motif are widespread, the H151R motif has segregated out of most species. Surprisingly, an uncharacterized orf in tarsiers (Loc-103275158) encodes R151 within a truncated A-23-like gene, which is in frame with short footprints of Tc5 and Tigger transposons (TE); the extant tarsier A-23 allele is totally missing exon-3 and part of exon-4; together, suggesting TE-mediated inactivation of an intact/ancestral A-23 allele. Since the only other (non-human) dual-motif A-like alleles are in gorilla, chimpanzee, and the Florida manatee, we speculate that dual-motif A alleles first emerged in the Afrotherian lineage and reappeared during the evolution of higher primates.
authors.affiliation: Xenolaüs Genetics LLC, 10880 Wilshire Blvd., Suite 1101, Los Angeles, CA, 90024, USA, jsmurray@xenolausgenetics.com.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Murray
mesh_terms: D000483:Alleles; D020816:Amino Acid Motifs / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000737:chemistry / Q000235:genetics; D004251:DNA Transposable Elements / Q000235:genetics*; D019143:Evolution, Molecular; D006071:Gorilla gorilla; D015234:HLA-A Antigens / Q000145:classification / Q000235:genetics*; D006639:Histidine / Q000737:chemistry / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D002679:Pan troglodytes; D010802:Phylogeny; D011323:Primates; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid
chemical_list: D004251:DNA Transposable Elements; D015234:HLA-A Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D006639:Histidine; D001120:Arginine