Transmembrane domain length variation in the evolution of major histocompatibility complex class I genes.

Abstract

The fifth exons of major histocompatibility complex (MHC) class I genes encode a transmembrane domain (TM) that is largely responsible for class I antigen cell-surface expression usually through conventional hydrophobic amino acid-membrane interactions or, less often, through phosphatidylinositol linkage. In this report we show that Peromyscus lucopus, a Cricetidae rodent, has MHC class I genes (Pele-A genes) encoding three distinct sizes of TMs. Increases in TM lengths were due to tandem duplications ofsequences similar to human hypervariable minisatellite repeats and the A chi site. We discerned remnants of a similar duplication event in comparable rodent and primate MHC class I genes. Furthermore, several duplications and deletions appear to have occurred independently in H-2, RTI, Pele-A, and ChLA genes in near-identical positions. Accumulated data suggests that sequences in the fifth exon of MHC class I genes may, therefore, constitute a mutational or recoombinational hot spot that is mediated by minisatellite-and chi-like sequences imbedded within the coding region. The MHC class I genes may thus have recruited "selfish" DNA in their evolution to encode cell surface proteins. Expression of Pele-A genes was examined by the polymerase chain reaction (PCR) using oligonucleotide primers specific for exon 4 and 5 sequences. The PCR product sizes indicated that genes encoding each TM domain length are ubiquitously transcribed.

Evolutionary History of MHC Class I Genes in the Mammalian Order Perissodactyla

“…some intragroup variation (group A) it is clear that this trait is not necessarily a good phylogenetic marker. Small variations in MHC class I gene TM length have been observed in other species, and it has been suggested that this area represents a hotspot for recombination and so is particularly susceptible to tandem duplications and deletions (Crew et al 1991), although we found no evidence of these processes here.…”

Characterization of MHC class I alleles in sooty mangabeys as a tool for evaluating cellular immunity in natural hosts of SIV infection

“…The transmembrane domain of Ceat-B*1101 was unusual in that there was a three amino acid insertion of alanine, valine, valine (AVV) which appeared to be due to a tandem duplication (Figure 1). A nine base pair duplication in the transmembrane domain of MHC class I genes has been reported in chimpanzee B-locus alleles and rodent MHC class I genes (Mayer et al 1988, Crew et al 1991). It is noteworthy that the duplication (AVV) in the chimpanzee allele is similar to that observed in Ceat-B*1101 .…”

Nucleotide sequence and structural analysis of the rat RT1.E u and RT1.Aw3 l genes, and of genes related to RT1.O and RT1.C

“…The transmembrane region amino acid sequence is significantly different among most class I genes of the rat , yet the deduced amino acid sequence of the transmembrane region of Eu was identical to that of K. In addition, the organization of the repeat in the transmembrane region of both genes is more like that of the mouse than that of other class I genes of the rat (Brorson et al 1989;Crew et al 1991;Rothermel et al 1993). From the evolutionary point of view, therefore, there may have been a duplication of a common ancestral gene that gave rise to RT1.K and RT1.E u, which in turn gave rise to the class I genes in the A region and in the E/C region, respectively, by duplication and subsequent mutation or segmental exchange.…”