Evolution of major histocompatibility complex class I genes in Cetartiodactyls

Previous studies of cattle MHC have suggested the presence of at least four classical class I loci. Analysis of haplotypes showed that any combination of one, two or three genes may be expressed, although no gene is expressed consistently. The aim of this study was to examine the evolutionary relationships among these genes and to study their phylogenetic history in Cetartiodactyl species, including cattle and their close relatives. A secondary aim was to determine whether recombination had occurred between any of the genes. MHC class I data sets were generated from published sequences or by polymerase chain reaction from cDNA. Phylogenetic analysis revealed that MHC class I sequences from Cetartiodactyl species closely related to cattle were distributed among the main cattle gene "groups", while those from more distantly related species were either scattered (sheep, deer) or clustered in a species-specific manner (sitatunga, giraffe). A comparison between gene and species trees showed a poor match, indicating that divergence of the MHC sequences had occurred independently from that of the hosts from which they were obtained. We also found two clear instances of interlocus recombination among the cattle MHC sequences. Finally, positive natural selection was documented at positions throughout the alpha 1 and 2 domains, primarily on those amino acids directly involved in peptide binding, although two positions in the alpha 3 domain, a region generally conserved in other species, were also shown to be undergoing adaptive evolution.     

Role of nonclassical class I genes of the chicken major histocompatibility complex Rfp-Y locus in transplantation immunity

The chicken major histocompatibility complex (MHC) genes are organized into two genetically independent clusters which both possess class I and class II genes: the classical B complex and the Restriction fragment pattern-Y (Rfp-Y) complex. In this study, we have examined the role of Rfp-Y genes in transplantation immunity. For this we used three sublines, B19H1, B19H2 and B19H3, derived from a line fixed for B19. Southern blots, PCR-SSCP assays using primers specific for Rfp-Y genes, and Rfp-Y class I allele-specific sequencing show that the polymorphisms observed in B19H1, B19H2 and B19H3 are due to the presence of three different Rfp-Y haplotypes. The Rfp-Y class I (YF) alleles in these three haplotypes are highly polymorphic, and RT-PCR shows that at least two YF loci are expressed in each subline. The three sublines show Rfp-Y-directed alloreactivity in that Rfp-Y-incompatible skin grafts are rejected within 15 days, a rate intermediate between that seen in B-incompatible rejection (7 days) and that observed for grafts within the sublines (20 days). We conclude that Rfp-Y has an intermediate role in allograft rejection, likely to be attributable to polymorphism at the class I loci within this region.The sequence data reported are available in the GenBank database under the accession numbers AY257165 (YFVw*15), AY257166 (YFVw*16), AY257167 (YFVIw*15), AY257168 (YFVIw*17), AY257169 (YFw*16), and AY257170 (YFw*17)     

Origin and evolution of the major histocompatibility complex class I region in eutherian mammals

Major histocompatibility complex (MHC) genes in vertebrates are vital in defending against pathogenic infections. To gain new insights into the evolution of MHC Class I (MHCI) genes and test competing hypotheses on the origin of the MHCI region in eutherian mammals, we studied available genome assemblies of nine species in Afrotheria, Xenarthra, and Laurasiatheria, and successfully characterized the MHCI region in six species. The following numbers of putatively functional genes were detected: in the elephant, four, one, and eight in the extended class I region, and κ and β duplication blocks, respectively; in the tenrec, one in the κ duplication block; and in the four bat species, one or two in the β duplication block. Our results indicate that MHCI genes in the κ and β duplication blocks may have originated in the common ancestor of eutherian mammals. In the elephant, tenrec, and all four bats, some MHCI genes occurred outside the MHCI region, suggesting that eutherians may have a more complex MHCI genomic organization than previously thought. Bat‐specific three‐ or five‐amino‐acid insertions were detected in the MHCI α1 domain in all four bats studied, suggesting that pathogen defense in bats relies on MHCIs having a wider peptide‐binding groove, as previously assayed by a bat MHCI gene with a three‐amino‐acid insertion showing a larger peptide repertoire than in other mammals. Our study adds to knowledge on the diversity of eutherian MHCI genes, which may have been shaped in a taxon‐specific manner.     

Composite origin of major histocompatibility complex genes

Major histocompatibility complex WHO genes have now been cloned from representatives of all vertebrate classes except Agnatha. The recent accumulation of sequence data has given great insight into the course of evolution of these genes. Although the primary structure of the MHC genes varies greatly from class to class and also within the individual classes, the general features of the tertiary and quaternary structure have been conserved remarkably well during more than 400 million years.of evolution. The ancestral MHC genes may have been assembled from at least three structural elements derived from different gene families. Class II MHC genes appear to have been assembled first, and then to have given rise to class I genes.     

Reptilian class I major histocompatibility complex genes reveal conserved elements in class I structure

The polymerase chain reaction was used to isolate clones with class I major histocompatibility complex sequences from fish (carp), amphibian (axolotl), and two species of reptile (lizard and snake). The lizard and snake clones were used to isolate class I cDNA clones. All the sequence showed the expected evolutionary relatedness. The carp and axolotl clones and one lizard cDNA clone lacked the first systeine in the ₃ domain which in other class I heavy chains forms an intradomain disulfide bond. A small number of amino acid residues are conserved in the class I heavy chain sequences from all five classes of vertebrates. In the first two domains they are symmetrically clustered and contribute to intra-and interdomain contacts. None of these invariant residues are at peptide-binding, T-cell receptor-interacting, or CD8-binding positions.The nucleotide sequence data reported in this paper have been submitted to the GenBank nucleotide sequence database and have been assigned the accession numbers: A2, M81089; C4,M8109 M81092; S1, M81093; LC1, M81094; LC5, M81095; LC13, M81096; LC25, M81097; LC27, M81098; SCI, M81099; SC2, M81100.     

Evolutionary relationships of major histocompatibility complex class I genes in simian primates

New World monkeys (NWMs) occupy a critical phylogenetic position in elucidating the evolutionary process of major histocompatibility complex (MHC) class I genes in primates. From three subfamilies of Aotinae, Cebinae, and Atelinae, the 5'-flanking regions of 18 class I genes are obtained and phylogenetically examined in terms of Alu/LINE insertion elements as well as the nucleotide substitutions. Two pairs of genes from Aotinae and Atelinae are clearly orthologous to human leukocyte antigen (HLA) -E and -F genes. Of the remaining 14 genes, 8 belong to the distinct group B, together with HLA-B and -C, to the exclusion of all other HLA class I genes. These NWM genes are classified into four groups, designated as NWM-B1, -B2, -B3, and -B4. Of these, NWM-B2 is orthologous to HLA-B/C. Also, orthologous relationships of NWM-B1, -B2, and -B3 exist among different families of Cebidae and Atelidae, which is in sharp contrast to the genus-specific gene organization within the subfamily Callitrichinae. The other six genes belong to the distinct group G. However, a clade of these NWM genes is almost equally related to HLA-A, -J, -G, and -K, and there is no evidence for their orthologous relationships to HLA-G. It is argued that class I genes in simian primates duplicated extensively in their common ancestral lineage and that subsequent evolution in descendant species has been facilitated mainly by independent loss of genes.     

Evolution of major histocompatibility complex class I genes in the sable Martes zibellina (Carnivora,Mustelidae)

The molecules encoded by major histocompatibility complex (MHC) genes play an essential role in the adaptive immune response among vertebrates. We investigated the molecular evolution of MHC class I genes in the sable Martes zibellina. We isolated 26 MHC class I sequences, including 12 putatively functional sequences and 14 pseudogene sequences, from 24 individuals from two geographic areas of northeast China. The number of putatively functional sequences found in a single individual ranged from one to five, which might be at least 1–3 loci. We found that both balancing selection and recombination contribute to evolution of MHC class I genes in M. zibellina. In addition, we identified a candidate nonclassical MHC class I lineage in Carnivora, which may have preceded the divergence (about 52–57 Mya) of Caniformia and Feliformia. This may contribute to further understanding of the origin and evolution of nonclassical MHC class I genes. Our study provides important immune information of MHC for M. zibellina, as well as other carnivores.     

Generation of major histocompatibility complex class I antigens

Presentation of antigenic peptides by major histocompatibility complex (MHC) class I molecules on the surface of antigen-presenting cells is an effective extracellular representation of the intracellular antigen content. The intracellular proteasome-dependent proteolytic machinery is required for generating MHC class I-presented peptides. These peptides appear to be derived mainly from newly synthesized defective ribosomal products, ensuring a rapid cytotoxic T lymphocyte-mediated immune response against infectious pathogens. Here we discuss the generation of MHC class I antigens on the basis of the currently understood molecular, biochemical and cellular mechanisms.     

Evolution of the major histocompatibility complex: a hundred-fold amplification of MHC class I genes in the African pigmy mouse Nannomys setulosus

The genome of the African murine rodent Nannomys setulosus was found to harbor several thousand major histocompatibility complex (MHC) class I genes instead of the 30–40 genes found in conventional laboratory mice, which are mostly of Mus musculus domesticus origin. Other genes of N. setulosus, either functionally or physically linked to class I genes, are not amplified. Amplified genes derive from as few as three ancestors and amplification has likely occured after the divergence of the two Nannomys species, N. setulosus and N. minutoides, which took place about three million years ago. Amplified genes are mostly pseudogenes. Statistical analysis of dinucleotide frequencies leads us to propose that inactivation of the genes has occured through the repeat induced mutation process, a possible newcomer in the evolution of the MHC.The nucleotide sequence data reported in this paper have been submitted to the EMBL nucleotide data library and have been assigned the accession numbers X61685 and X61686. Correspondence to : G. Gachelin.     

HIV Nef-mediated major histocompatibility complex class I down-modulation is independent of Arf6 activity

HIV Nef has a number of important biological effects, including the down-modulation of several immunological important molecules (CD4, major histocompatibility complex [MHC] class I). Down-modulation of CD4 seems to be via clathrin-dependent endocytosis, whereas down-modulation of MHC class I remains unexplained. Several mutant proteins, including mutations in the small GTPase Arf6, have been used to probe membrane traffic pathways. One such mutant has recently been used to propose that Nef acts through Arf6 to activate the endocytosis of MHC class I. Here, we show that MHC class I down-modulation is unaffected by other Arf6 mutants that provide more specific perturbations in the GDP-GTP cycling of Arf6. Inhibition of phosphatidylinositol-3-phosphate kinase, an upstream activator of Arf6, also had no effect on the internalization step, but its activity is required to direct MHC class I to the trans-Golgi network. We conclude that the apparent Arf6 dependency of Nef-mediated MHC class I down-modulation is due to nonspecific perturbations in membrane traffic.     

Cloning of the bovine major histocompatibility complex class II genes

Summary. Class II genes of the bovine major histocompatibility complex (MHC) have been cloned from a genomic library. The library was constructed in the bacteriophage Λ vector EMBL3 and comprises approximately 10 times the equivalent of the haploid genome. Half the library was screened with the human DQA, DQB, DRA and DRB cDNA probes. Of the 100 positively hybridizing phage clones, 37 were eventually fully characterized and mapped by means of Southern blot analysis. The exons encoding the first, second and transmembrane domain of all different A and B genes were subcloned and mapped in more detail. These analyses showed that these 37 clones were derived from five different A and 10 different B genes. The hybridization studies indicate that we have cloned and mapped two DQA genes, one DRA gene, two other A genes, four DQB genes, three DRB genes and three other B genes. Since the library was made from a heterozygous animal, this would suggest that there are at least one DQA, one DRA one other undefined A, two DQB, two DRB and one or two other undefined B genes in the haploid genome of Holstein Friesian cattle.     

Cloning of the bovine major histocompatibility complex class II genes

Class II genes of the bovine major histocompatibility complex (MHC) have been cloned from a genomic library. The library was constructed in the bacteriophage lambda vector EMBL3 and comprises approximately 10 times the equivalent of the haploid genome. Half the library was screened with the human DQA, DQB, DRA and DRB cDNA probes. Of the 100 positively hybridizing phage clones, 37 were eventually fully characterized and mapped by means of Southern blot analysis. The exons encoding the first, second and transmembrane domain of all different A and B genes were subcloned and mapped in more detail. These analyses showed that these 37 clones were derived from five different A and 10 different B genes. The hybridization studies indicate that we have cloned and mapped two DQA genes, one DRA gene, two other A genes, four DQB genes, three DRB genes and three other B genes. Since the library was made from a heterozygous animal, this would suggest that there are at least one DQA, one DRA one other undefined A, two DQB, two DRB and one or two other undefined B genes in the haploid genome of Holstein Friesian cattle.