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.

Contrasting patterns of selection acting on MHC class I and class II DRB genes in the Alpine marmot (Marmota marmota)

“…, 1990; Lobigs et al. , 1995), where two to three loci were found, although our study is the first to document multiple MHC class I loci in Sciuridae (Wettstein et al. , 1996; Yang et al.…”

“…2). Although relatively short sequence analysed does not allow drawing firm conclusions about time‐order of duplications, especially that strong positive selection may interfere with phylogenetic inference (Wettstein et al. , 1996), the grouping of DRB2 with Dipodomys suggests that duplication occurred before the split of Sciuromorpha from other rodent suborders and that Mama ‐DRB2 ortholog has subsequently been lost in Spermophilus .…”