MHC polymorphism in island populations of mice.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to F Figueroa.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Two populations of the wild house mouse, Mus domesticus, found living close to each other (one inhabited a chicken coop and the other an open field at the Educational Farm of the Hebrew University of Jerusalem, East Talpiot, Jerusalem) were studied for their H-2 polymorphism. These two populations were selected because they are well characterized in terms of their ecological parameters; they have been under continuous surveillance for several years. Twenty-seven H-2 homozygous lines were produced by mating wild mice from these two populations with laboratory strains. The H-2w homozygotes were then characterized by serological typing with monoclonal and polyclonal antibodies specific for the known allomorphs controlled by the class I H-2K and H-2D loci or the class II H-2A and H-2E loci. They were also used as donors for immunizations and for the selection of antisera defining the H-2 haplotypes carried by these lines. Four new H-2 haplotypes could be identified: H-2w82 (Kw16 Dw82), H-2w83 (Kw83 Dw16), H-2w84 (Kw84 Dw84), and H-2w85 (Kw83 Dw84), the last haplotype being a recombinant derived from H-2w83 and H-2w84. Antisera defining the new haplotypes were then used for a study of the wild populations. This study revealed that the populations contain only the four identified H-2 haplotypes, having three alleles at the H-2K locus (Kw16, Kw83, Kw84) and three alleles at the H-2D locus (Dw16, Dw82, and Dw84). The alleles occur in the populations with a frequency of 0.12-0.54. There were no significant differences in gene frequencies between the two populations, and the allele frequencies remained more or less stable. There was a significant excess of heterozygotes for at least some of the genes, compared with the frequency expected from Hardy-Weinberg equilibrium. The same antisera were also used to type other populations in the vicinity of Jerusalem. In one population, located 30 km west of Jerusalem, the mice failed to react with any of the reagents. In the other two populations, located 15 km west and 40 km northeast of Jerusalem, three of the four H-2 haplotypes found in East Talpiot were present at high frequencies. It appears, therefore, that only three main H-2 haplotypes and two or three minor ones are present in the area around Jerusalem. This study thus provides the first example of a large mainland population in which the H-2 polymorphism is comparable to that of many other non-H-2 loci.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The major histocompatibility complex is a group of closely linked loci that code for molecules used by T-lymphocytes as context for the recognition of antigens. The loci fall into two classes: I, coding for molecules used as context by cytotoxic T-lymphocytes and II, used as context by helper and other regulatory T-cells. The Mhc is present in all mammals and perhaps all vertebrates. Some of the Mhc loci are highly polymorphic, while others are not. This article will summarize what is known about the genetic organization of the Mhc in different species and will discuss the selection pressures acting on the individual loci and the tempo and the mechanisms of their evolution.
Genomic DNA was isolated from 29 t strains and 4 congenic lines of mice, digested with restriction endonucleases, and hybridized with a probe representing the complement component 4 (C4) gene. All but one of the enzymes revealed restriction fragment length polymorphism in this sample of C4-related genes. Double digestion analysis suggested the presence of three C4 gene copies in some of the t chromosomes and two copies in others. The enzymes distinguished 16 different haplotypes among the 33 strains tested. Based on their restriction fragment length patterns, the t strains could be divided into four groups with strains in each group more closely related to each other with respect to their C4-region genes than strains belonging to different groups. At least three of these four groups represent different branches of the evolutionary tree constructed for the t chromosomes. The C4-related genes of the chromosomes are in strong linkage disequilibrium with the class II genes of the H-2 complex. Typing for the Ss and Slp allotypes of C4 has revealed the presence of the Ss1 phenotype in two t strains and of the Slpa phenotype in one strain.
DNA was isolated from 75 mouse strains carrying classical H-2 haplotypes as well as haplotypes derived from wild mice. The DNA was digested with three restriction endonucleases, Bst EII, Eco RI, and Bam HI, the digests hybridized, using the Southern blotting technique, with probes for the class II genes A alpha, A beta, E alpha, and E beta, and the restriction fragment length polymorphism at these loci determined. The analysis revealed that the most polymorphic of the four loci is A beta, followed by E beta, and, at a different level, by E alpha and A alpha. There is a large difference in the degree of polymorphism between the A beta and E beta genes, on the one hand, and the A alpha and E alpha genes, on the other hand. There is no difference in the degree of polymorphism between the A alpha and E alpha genes. These findings do not substantiate previous postulates of a high A alpha polymorphism and they do not agree with the hypothesis that the class II region is divided into highly polymorphic centromeric and less polymorphic telomeric subregions. Rather, it appears that the differences in the degree of polymorphism of the different segments of the class II region are determined by the class II loci themselves. The polymorphism of the less polymorphic class II genes is, however, still greater than the polymorphism of certain other genes on chromosome 17, notably the alpha 4-globin pseudogene. The distribution of polymorphisms at the A beta and E beta loci suggests that even populations occupying relatively small geographical regions differ in alleles at these loci. Sharing of A beta alleles between unrelated populations is yet to be detected. A certain degree of linkage disequilibrium exists among the A alpha, A beta, and E beta loci; by contrast, the E alpha locus appears to vary largely independently of the other class II loci.
The major histocompatibility complex (Mhc) is a group of loci coding for lymphocyte membrane glycoproteins that provide the context for the recognition of foreign antigens in the initial phase of the immune response. The complex contains a large number of loci, some of which are highly polymorphic. The complexity and polymorphism pose a number of questions concerning the evolution of the Mhc. In an attempt to answer some of these questions, we have begun to study the Mhc of the mole-rat, Spalax ehrenbergi, a rodent representing a complex of sibling species occupying ecologically and geographically clearly delineated regions within the borders of Israel. In an earlier publication we identified the Spalax major histocompatibility (Smh) complex serologically and biochemically. Here, we analyze the Smh by Southern blotting of DNA fragments produced by restriction enzyme digestion. The fragments were hybridized to mouse probes specific for class I, class II, and C4 genes. The analysis has revealed that the Smh complex contains as many class I genes as the mouse does and that these genes are polymorphic. The number of class II genes could not be determined with certainty, but it is probably not greater than in the mouse. Polymorphism was also detected at the loci coding for the complement component 4 (C4), which are probably closely linked to the Smh complex. The polymorphism of mole-rat class I loci contrasts with the reported monomorphism of these loci in the Syrian hamster. Since the mole-rat leads a solitary, subterranean life, as the Syrian hamster does, ecology cannot be an explanation for the lack of class I polymorphism in the latter species.
Virtually all wild mouse populations carry t haplotypes that cause embryonic lethality or semilethality, distortion of segregation ratios, suppression of crossing-over, and male sterility. The t complex of genes is located on chromosome 17, closely linked to the H-2, the major histocompatibility complex of the mouse. The t haplotypes differ from each other not only in lethal genes they carry but also in their linked H-2 haplotypes. In this study, we compared the class II H-2 genes present on 31 t chromosomes extracted from wild populations in different parts of the world. The comparison was based on the analysis of DNA fragments obtained after digestion with restriction endonucleases. The results reveal the existence of three major groups of class II alleles representing main branches on the evolutionary tree of the t chromosomes. Alleles within each group are similar if not identical, although they are borne by chromosomes that have been separated in time and space. The presence of similar alleles in Mus musculus and Mus domesticus suggests that some of them may have been separated for more than 1 million years. This must also be the minimal age of the t chromosomes but, because at least two of the three main branches appear to be related in their origin, the actual age of t chromosomes could be much greater. The observations support the proposal that H-2 genes evolve slowly.
Explore the source record for details and available documents.
Thirty-three mouse strains carrying t haplotypes were typed with a large battery of monoclonal and polyclonal antibodies specific for class I and class II antigens controlled by the H-2 complex. Among these t haplotypes were representatives of the six complementation groups defined previously and of eight new groups defined by us recently. The typing resulted in the identification of the H-2 haplotypes of these strains and of their alleles at K, D, A, and E loci. Nineteen of the 33 strains proved to carry a mutation that prevents the expression of the E molecule on the cell surface. All H-2 haplotypes of the t strains are related in terms of sharing certain antigenic determinants, most of which have not, as yet, been found in inbred strains or in wild mice that do not carry t haplotypes. According to the degree of serological relatedness, the haplotypes can be arranged into a pedigree presumably reflecting the evolutionary history of the t chromosomes. The ancestral t chromosome from which the 33 chromosomes derive was presumably present in the mouse population before the divergence of the Mus musculus and Mus domesticus species. The E0 mutation, too, is apparently ancient because it occurs in different branches of the evolutionary tree.
The mole-rat, Spalax ehrenbergi, is a complex subterranean rodent species whose habitat is restricted largely to the Middle East and North Africa. We typed over 50 mole-rats with mouse monoclonal and polyclonal antibodies specific for class I and class II major histocompatibility complex (Mhc) molecules. Some of these antibodies were produced against mouse Mhc molecules, others against Mhc molecules of other species. About 25% of the antibodies reacted with mole-rat lymphocytes in the cytotoxic test. Some of the serologically positive antibodies precipitated from a glycoprotein pool of mole-rat spleen cell molecules that corresponded in size with class I and class II molecules of other species. We conclude, therefore, that mole-rats, like other mammals, possess the Mhc which consists of class I and class II loci. We call this Mhc Spalax major histocompatibility (Smh) complex. The occurrence of a large number of different serotypes among the tested animals suggests that Smh loci are polymorphic. This Mhc polymorphism of the mole-rat contrasts with the monomorphism or oligomorphism of the Syrian hamster, a rodent with a similar ecology. Thus far no qualitative correlation could be found between Smh polymorphism and chromosome variation described in this superspecies.
Explore the source record for details and available documents.
In this second part of the Second Listing, we describe genes that constitute the H-2 complex proper. Here, we define the complex functionally as consisting of class I and class II loci (see Klein et al. 1983a). The H-2-associated complement loci and the Neu-1 locus have been described in the first part of the Second Listing (Klein et al. 1982), but for completeness we list them here again in some of the tables. We include into the H-2 complex the cluster of Qa and Tla loci, which we consider as class I loci (Klein et al. 1983). The genetic map of the definitely established loci appears in Figure 1 and is based on the recent results of molecular genetics studies (Steinmetz et al. 1982 a, b). For historical reasons we also describe loci (regions, subregions) that were once thought to be part of the H-2 complex but either they have since been withdrawn, or their actual existence is at present uncertain. We first list loci (regions, subregions) that have been designated by capital letters (we call it Madman's Alphabet because of the frivolity with which symbols have been introduced and then withdrawn again), and then other loci believed to be associated with the H-2 complex. As in the First Listing (Klein et al. 1978), the core of the review in the Second Listing constitutes the tables of H-2 haplotypes, antigens, and determinants.
Wild mice captured in Texas, Scotland, Federal Republic of Germany, Denmark, Spain, Greece, Israel, Egypt, and Chile were mated to inbred strains and through successive backcross matings and H-2 typing lines homozygous for wild-derived H-2, haplotypes were established. The lines, which are neither congenic nor inbred, were then typed with antibodies defining known H-2 alleles at class I and class II loci. In addition, antisera were produced by the immunization of inbred strains with tissues of the new lines. Sixteen of the lines were characterized in this manner. The characterization resulted in the identification of 16 new H-2 haplotypes, 11 new K alleles, 10 new D alleles, and 21 new class I antigenic determinants, most of them of the private type. Most of the haplotypes represent natural recombinants sharing segments of the H-2 complex with previously identified haplotypes. A number of haplotypes are recombinants between the K and the A loci, which in genetic studies have proved difficult to separate. The lines, however, also provide evidence for preservation of blocks of genes in the H-2 complex, particularly in the class II region. Some of class I alleles previously found in wild mice from Michigan have now been found again in these mice. Several class II alleles of these lines appear to be the same as those found in inbred strains. Identical or nearly identical class I and class II alleles thus commonly occur in different populations. These findings strengthen the argument that in populations, H-2 alleles are relatively stable.
Explore the source record for details and available documents.