scholarly journals The Implications of Intergenic Polymorphism for Major Histocompatibility Complex Evolution

Genetics ◽  
2000 ◽  
Vol 156 (2) ◽  
pp. 867-877 ◽  
Author(s):  
Colm O'hUigin ◽  
Yoko Satta ◽  
Anja Hausmann ◽  
Roger L Dawkins ◽  
Jan Klein
Keyword(s):  
Major Histocompatibility Complex ◽  
Least Squares ◽  
Balancing Selection ◽  
Low Frequency ◽  
Least Squares Estimate ◽  
B Locus ◽  
Histocompatibility Complex ◽  
Intergenic Regions ◽  
Major Histocompatibility Complex Evolution ◽  
High Degree

Abstract A systematic survey of six intergenic regions flanking the human HLA-B locus in eight haplotypes reveals the regions to be up to 20 times more polymorphic than the reported average degree of human neutral polymorphism. Furthermore, the extent of polymorphism is directly related to the proximity to the HLA-B locus. Apparently linkage to HLA-B locus alleles, which are under balancing selection, maintains the neutral polymorphism of adjacent regions. For these linked polymorphisms to persist, recombination in the 200-kb interval from HLA-B to TNF must occur at a low frequency. The high degree of polymorphism found distal to HLA-B suggests that recombination is uncommon on both sides of the HLA-B locus. The least-squares estimate is 0.15% per megabase with an estimated range from 0.02 to 0.54%. These findings place strong restrictions on possible recombinational mechanisms for the generation of diversity at the HLA-B.

Recombination, Balancing Selection and Phylogenies in MHC and Self-Incompatibility Genes

Genetics ◽  
2001 ◽  
Vol 159 (4) ◽  
pp. 1833-1844 ◽  
Author(s):  
Mikkel H Schierup ◽  
Anders M Mikkelsen ◽  
Jotun Hein
Keyword(s):  
Major Histocompatibility Complex ◽  
Phylogenetic Tree ◽  
Balancing Selection ◽  
Nucleotide Sequences ◽  
Recombination Process ◽  
Self Incompatibility ◽  
Selection Coefficient ◽  
Histocompatibility Complex ◽  
A Site ◽  
Possible Cause

AbstractUsing a coalescent model of multiallelic balancing selection with recombination, the genealogical process as a function of recombinational distance from a site under selection is investigated. We find that the shape of the phylogenetic tree is independent of the distance to the site under selection. Only the timescale changes from the value predicted by Takahata's allelic genealogy at the site under selection, converging with increasing recombination to the timescale of the neutral coalescent. However, if nucleotide sequences are simulated over a recombining region containing a site under balancing selection, a phylogenetic tree constructed while ignoring such recombination is strongly affected. This is true even for small rates of recombination. Published studies of multiallelic balancing selection, i.e., the major histocompatibility complex (MHC) of vertebrates, gametophytic and sporophytic self-incompatibility of plants, and incompatibility of fungi, all observe allelic genealogies with unexpected shapes. We conclude that small absolute levels of recombination are compatible with these observed distortions of the shape of the allelic genealogy, suggesting a possible cause of these observations. Furthermore, we illustrate that the variance in the coalescent with recombination process makes it difficult to locate sites under selection and to estimate the selection coefficient from levels of variability.

Highly polymorphic genetic markers in meadow voles (Microtus pennsylvanicus) revealed by a murine major histocompatibility complex (MHC) probe

1991 ◽  
Vol 69 (1) ◽  
pp. 213-220 ◽  
Author(s):  
Yves Plante ◽  
Peter T. Boag ◽  
Bradley N. White ◽  
Rudy Boonstra
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class Ii ◽  
Population Sample ◽  
Meadow Vole ◽  
Major Histocompatibility ◽  
Genomic Libraries ◽  
Histocompatibility Complex ◽  
Length Polymorphisms ◽  
Species Specific ◽  
High Degree

We performed cross-species hybridization at the major histocompatibility complex (MHC) to evaluate the ability of murine probes to reveal polymorphism in wild meadow vole populations. Genomic hybridization of a mouse MHC class II I-Aα cDNA revealed extensive restriction fragment length polymorphisms when meadow vole genomic DNA was cleaved with BamHI EcoRI, HindIII, or HincII. The polymorphisms were interpreted by analyzing 10 half-sib families, comprising 6 sires, 10 dams, and 34 offspring. At least 26 different alleles were found with HincII in the family material, and the estimated heterozygosity at those sites is 96%. Several other alleles were found in a population sample. The high degree of genetic variation revealed by this system indicates that it is a viable alternative to multilocus "genetic fingerprinting" probes for the analysis of small mammal pedigrees or strains. Several mouse MHC probes are readily available and they provide a quick route to screening populations and remove the need to extract species-specific markers from genomic libraries.

Natural selection at the class II major histocompatibility complex loci of mammals

1994 ◽  
Vol 346 (1317) ◽  
pp. 359-367 ◽  
Keyword(s):  
Major Histocompatibility Complex ◽  
Natural Selection ◽  
Balancing Selection ◽  
Synonymous Substitution ◽  
Class Ii ◽  
Class I ◽  
Major Histocompatibility ◽  
Class I Mhc ◽  
Histocompatibility Complex ◽  
Class Ii Mhc

The role of natural selection at major histocompatibility complex (MHC) loci was studied by analysis of molecular sequence data from mammalian class II MHC loci. As found previously for the class I MHC molecule and a hypothetical model of the class II molecule, the rate of non-synonymous nucleotide substitution exceeded that of synonymous substitution in the codons encoding the antigen recognition site of polymorphic class II molecules. This pattern is evidence that the polymorphism at these loci is maintained by a form of balancing selection, such as overdominant selection. By contrast, in the case of monomorphic class II loci, no such enhancement of the rate of non-synonymous substitution was observed. Phylogenetic analysis indicates that, in contrast to monomorphic (‘non-classical’) class I MHC loci, some monomorphic class II loci of mammals are quite ancient. The DMA and DMB loci, for example, diverged before all other known mammalian class II loci, possibly before the divergence of tetrapods from bony fishes. Analysis of the patterns of sharing of polymorphic residues at class II MHC loci by mammals of different species revealed that extensive convergent evolution has occurred at these loci; but no support was found for the hypothesis that MHC polymorphisms have been maintained since before the divergence of orders of eutherian mammals.

scholarly journals Major histocompatibility complex (MHC) heterozygote superiority to natural multi-parasite infections in the water vole ( Arvicola terrestris )

2008 ◽  
Vol 276 (1659) ◽  
pp. 1119-1128 ◽  
Author(s):  
M.K Oliver ◽  
S Telfer ◽  
S.B Piertney
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class Ii ◽  
Balancing Selection ◽  
Parasite Burden ◽  
Island Population ◽  
Water Vole ◽  
Immune Recognition ◽  
Major Histocompatibility ◽  
Arvicola Terrestris ◽  
Histocompatibility Complex

The fundamental role of the major histocompatibility complex (MHC) in immune recognition has led to a general consensus that the characteristically high levels of functional polymorphism at MHC genes is maintained by balancing selection operating through host–parasite coevolution. However, the actual mechanism by which selection operates is unclear. Two hypotheses have been proposed: overdominance (or heterozygote superiority) and negative frequency-dependent selection. Evidence for these hypotheses was evaluated by examining MHC–parasite relationships in an island population of water voles ( Arvicola terrestris ). Generalized linear mixed models were used to examine whether individual variation at an MHC class II DRB locus explained variation in the individual burdens of five different parasites. MHC genotype explained a significant amount of variation in the burden of gamasid mites, fleas ( Megabothris walkeri ) and nymphs of sheep ticks ( Ixodes ricinus ). Additionally, MHC heterozygotes were simultaneously co-infected by fewer parasite types than homozygotes. In each case where an MHC-dependent effect on parasite burden was resolved, the heterozygote genotype was associated with fewer parasites, and the heterozygote outperformed each homozygote in two of three cases, suggesting an overall superiority against parasitism for MHC heterozygote genotypes. This is the first demonstration of MHC heterozygote superiority against multiple parasites in a natural population, a mechanism that could help maintain high levels of functional MHC genetic diversity in natural populations.

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