Balancing selection and heterozygote advantage in major histocompatibility complex loci of the bottlenecked Finnish wolf population

2014 ◽  
Vol 23 (4) ◽  
pp. 875-889 ◽  
Author(s):  
A. K. Niskanen ◽  
L. J. Kennedy ◽  
M. Ruokonen ◽  
I. Kojola ◽  
H. Lohi ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Balancing Selection ◽  
Heterozygote Advantage ◽  
Major Histocompatibility ◽  
Wolf Population ◽  
Histocompatibility Complex

scholarly journals Polymorphism and balancing selection at major histocompatibility complex loci.

Genetics ◽  
1992 ◽  
Vol 130 (4) ◽  
pp. 925-938 ◽  
Author(s):  
N Takahata ◽  
Y Satta ◽  
J Klein
Keyword(s):  
Major Histocompatibility Complex ◽  
Dna Sequences ◽  
Balancing Selection ◽  
Heterozygote Advantage ◽  
Nucleotide Substitution Rate ◽  
Major Histocompatibility ◽  
Effective Population ◽  
Nucleotide Substitutions ◽  
Mhc Genes ◽  
Histocompatibility Complex

Abstract Amino acid replacements in the peptide-binding region (PBR) of the functional major histocompatibility complex (Mhc) genes appear to be driven by balancing selection. Of the various types of balancing selection, we have examined a model equivalent to overdominance that confers heterozygote advantage. As discussed by A. Robertson, overdominance selection tends to maintain alleles that have more or less the same degree of heterozygote advantage. Because of this symmetry, the model makes various testable predictions about the genealogical relationships among different alleles and provides ways of analyzing DNA sequences of Mhc alleles. In this paper, we analyze DNA sequences of 85 alleles at the HLA-A, -B, -C, -DRB1 and -DQB1 loci with respect to the number of alleles and extent of nucleotide differences at the PBR, as well as at the synonymous (presumably neutral) sites. Theory suggests that the number of alleles that differ at the sites targeted by selection (presumably the nonsynonymous sites in the PBR) should be equal to the mean number of nucleotide substitutions among pairs of alleles. We also demonstrate that the nucleotide substitution rate at the targeted sites relative to that of neutral sites may be much larger than 1. The predictions of the presented model are in surprisingly good agreement with the actual data and thus provide means for inferring certain population parameters. For overdominance selection in a finite population at equilibrium, the product of selection intensity (s) against homozygotes and the effective population size (N) is estimated to be 350-3000, being largest at the B locus and smallest at the C locus. We argue that N is of the order of 10(5) and s is several percent at most, if the mutation rate per site per generation is 10(-8).

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.

scholarly journals Quantitative disease resistance: to better understand parasite-mediated selection on major histocompatibility complex

2011 ◽  
Vol 279 (1728) ◽  
pp. 577-584 ◽  
Author(s):  
Helena Westerdahl ◽  
Muhammad Asghar ◽  
Dennis Hasselquist ◽  
Staffan Bensch
Keyword(s):  
Major Histocompatibility Complex ◽  
Disease Resistance ◽  
Balancing Selection ◽  
Quantitative Resistance ◽  
Infection Intensity ◽  
Positive Association ◽  
Major Histocompatibility ◽  
Quantitative Disease Resistance ◽  
Histocompatibility Complex ◽  
Descriptive Framework

We outline a descriptive framework of how candidate alleles of the immune system associate with infectious diseases in natural populations of animals. Three kinds of alleles can be separated when both prevalence of infection and infection intensity are measured—qualitative disease resistance, quantitative disease resistance and susceptibility alleles. Our descriptive framework demonstrates why alleles for quantitative resistance and susceptibility cannot be separated based on prevalence data alone, but are distinguishable on infection intensity. We then present a case study to evaluate a previous finding of a positive association between prevalence of a severe avian malaria infection (GRW2, Plasmodium ashfordi ) and a major histocompatibility complex (MHC) class I allele (B4b) in great reed warblers Acrocephalus arundinaceus . Using the same dataset, we find that individuals with allele B4b have lower GRW2 infection intensities than individuals without this allele. Therefore, allele B4b provides quantitative resistance rather than increasing susceptibility to infection. This implies that birds carrying B4b can mount an immune response that suppresses the acute-phase GRW2 infection, while birds without this allele cannot and may die. We argue that it is important to determine whether MHC alleles related to infections are advantageous (quantitative and qualitative resistance) or disadvantageous (susceptibility) to obtain a more complete picture of pathogen-mediated balancing selection.

scholarly journals INITIAL CHARACTERIZATION OF MAJOR HISTOCOMPATIBILITY COMPLEX (MHC) CLASS IIB EXON 2 IN AN ENDANGERED RATTLESNAKE, THE EASTERN MASSASAUGA (SISTRURUS CATENATUS)

2014 ◽  
pp. 98-104 ◽  
Author(s):  
Collin P. Jaeger ◽  
Richard B. King ◽  
Melvin R. Duvall
Keyword(s):  
Major Histocompatibility Complex ◽  
Positive Selection ◽  
Balancing Selection ◽  
Population Level ◽  
Major Histocompatibility ◽  
Exon 2 ◽  
Conservation Implications ◽  
Histocompatibility Complex ◽  
Sistrurus Catenatus ◽  
Mhc Class Iib

Genes of the major histocompatibility complex (MHC) play an important role in the vertebrate immune system and exhibit remarkably high levels of polymorphism, maintained by strong balancing selection. While the conservation implications of MHC variation have been explored in a variety of vertebrates, non-avian reptiles (most notably snakes) have received less attention. To address this gap and take the first steps toward more extensive population-level analyses, we cloned and sequenced MHC IIB exon 2 in an endangered rattlesnake, the Eastern Massasauga (Sistrurus catenatus). Based on three individuals, we found evidence of at least four putatively functional loci. These sequences exhibited relatively high levels of variation and significantly higher rates of nonsynonymous to synonymous substitutions, especially within the antigen-binding sites, indicating strong positive selection. Phylogenetic analysis revealed a pattern of trans-species polymorphism, also suggesting positive selection. These results contribute to our understanding of MHC variation in non-avian reptiles and form a basis for more studies of MHC variation in snakes of conservation concern.

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