title: The divergence of major histocompatibility complex class I genes in Sciurus aberti.
abstract: Major histocompatibility complex (MHC) class I genes encode cell surface molecules that bind and present immunogenic peptides to cytolytic T lymphocytes. We have developed a model using the MHC (Scab) of tassel-eared squirrels, Sciurus aberti, to investigate the evolution of MHC genes in subspecies that have been effectively isolated in comparable, if not identical, environments. Class I cDNAs from single S. aberti aberti and S. aberti kaibabensis squirrels were cloned and sequenced. These two cDNA transcripts differed by nucleotide substitutions that were predominantly located in codons impacting the peptide binding site, and nonsynonymous substitutions exceeded synonymous substitutions at these sites. These sequences also differed by the insertion of two amino acids in a beta-strand adjacent to position 45 in pocket B of the peptide binding site that may result in a deeper pocket with altered peptide specificity. This indel is present in additional Scab class I sequences, and class I sequences in five subspecies carry identically sized insertions. Phylogenetic analyses of exons 2, 3, and 4 with neighbor-joining and maximum parsimony methods depict that Scab class I sequences diverged at a point intermediate between murid class I sequences and class I sequences of primates, carnivores, and artiodactyls. The relative relatedness of Scab class I sequences to those in the latter group appears to be founded in relative similarities in exons 2 and 3, which encode the peptide binding site. These results bring into question the use of a single model for rodent class I sequences. Moreover, they demonstrate that the inclusion of exons 2 and 3 in phylogenetic analyses of class I may obscure true phylogenetic relationships, perhaps due to convergence through strong selective pressure.
authors.affiliation: Department of Surgery, Mayo Foundation, Rochester, Minnesota 55905, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Wettstein
authors.forename: M
authors.initials: M
authors.lastname: Strausbauch
authors.forename: S L
authors.initials: SL
authors.lastname: Johnston
authors.forename: J
authors.initials: J
authors.lastname: States
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D008969:Molecular Sequence Data; D010802:Phylogeny; D012589:Sciuridae / Q000235:genetics* / Q000276:immunology*; D016415:Sequence Alignment; D017421:Sequence Analysis
chemical_list: D015395:Histocompatibility Antigens Class I