Major histocompatibility complex polymorphism: dynamics and consequences of parasite-mediated local adaptation in fishes

Parasitism is a common form of life and represents a strong selective pressure for host organisms. In response to this evolutionary pressure, vertebrates have developed genetically coded defences such as the major histocompatibility complex (MHC). Mechanisms of parasite-mediated selection not only maintain outstanding polymorphism in these genes but have also been proposed to further promote host population divergence and ultimately speciation because it can drive evolution of local adaptation in which MHC genes play a crucial role. This review first highlights the dynamics and complexity of parasite-mediated selection in natural systems, which not only depends on dominating parasite strategies and on the taxonomic diversity of the parasite community but also includes the differences in parasite communities between habitats and niches, creating divergent selection on locally adapted populations. Then the different ways in which MHC genes potentially allow vertebrates to respond to these dynamics and to adapt locally are outlined. Finally, it is proposed that varying selection strength in time and space may lead to variation in the strength of precopulatory reproductive isolation which has evolved to maintain local adaptation.     

Diversification of porcine MHC class II genes: evidence for selective advantage

The major histocompatibility complex (MHC) is an immunological gene-dense region of high diversity in mammalian species. Sus scrofa was domesticated by at least six independent events over Eurasia during the Holocene period. It has been hypothesized that the level and distribution of MHC variation in pig populations reflect genetic selection and environmental influences. In an effort to define the complexity of MHC polymorphisms and the role of selection in the generation of class II gene diversity (DQB, DRB1, and pseudogene ΨDRB3), DNA from globally distributed unrelated domestic pigs of European and Asian origins and a Suidae out-group was analyzed. The number of pseudogene alleles identified (ΨDRB3 33) was greater than those found in the expressed genes (DQB 20 and DRB1 23) but the level of observed heterozygosity (ΨDRB3 0.452, DQB 0.732, and DRB1 0.767) and sequence diversity (ΨDRB3 0.029, DQB 0.062, and DRB1 0.074) were significantly lower in the pseudogene, respectively. The substitution ratios reflected an excess of d _N (DQB 1.476, DRB1 1.724, and ΨDRB3 0.508) and the persistence of expressed gene alleles suggesting the influence of balancing selection, while the pseudogene was undergoing purifying selection. The lack of a clear MHC phylogeographic tree, coupled with close genetic distances observed between the European and Asian populations (DQB 0.047 and DRB1 0.063) suggested that unlike observations using mtDNA, the MHC diversity lacks phylogeographic structure and appears to be globally uniform. Taken together, these results suggest that, despite regional differences in selective breeding and environments, no skewing of MHC diversity has occurred. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Sequence variability analysis on major histocompatibility complex class II DRB alleles in three felines

The variation of the exon 2 of the major histo-compatibility complex (MHC) class II gene DRB locus in three feline species were examined on clouded leopard (Neofelis nebulosa), leopard (Panthera pardus) and Amur tiger (Panthera tigris altaica). A pair of degenerated primers was used to amplify DRB locus covering almost the whole exon 2. Exon 2 encodes the β1 domain which is the most variable fragments of the MHC class II molecule. Single-strand conformational polymorphism (SSCP) analysis was applied to detect different MHC class II DRB haplotypes. Fifteen recombinant plasmids for each individual were screened out, isolated, purified and sequenced finally. Totally eight distinct haplotypes of exon 2 were obtained in four individuals. Within 237 bp nucleotide sequences from four samples, 30 variable positions were found, and 21 putative peptide-binding positions were disclosed in 79 amino acid residues. The ratio of nonsynonymous substitutions (d _N ) was much higher than that of synonymous substitutions (d _S ), which indicated that balancing selection probably maintain the variation of exon 2. MEGA neighbor joining (NJ) and PAUP maximum parsimony (MP) methods were used to reconstruct phylogenetic trees among species, respectively. Results displayed a more close relationship between leopard and tiger; however, clouded leopard has a comparatively distant relationship form the other two. __________ Translated from Zoological Research, 2006, 27(2): 181-C188 [译自:动物学研究]     

Sequence variability analysis on major histocompatibility complex class Ⅱ DRB alleles in three felines

The variation of the exon 2 of the major histo-compatibility complex (MHC) class Ⅱ gene DRB locus in three feline species were examined on clouded leopard (Neofelis nebulosa), leopard (Panthera pardus) and Amur tiger (Panthera tigris altaica). A pair of degenerated primers was used to amplify DRB locus covering almost the whole exon 2. Exon 2 encodes the β1 domain which is the most vari-able fragments of the MHC class Ⅱ molecule. Single-strand conformational polymorphism (SSCP) analysis was applied to detect different MHC class Ⅱ DRB haplotypes. Fifteen recombinant plasmids for each individual were screened out, isolated, purified and sequenced finally. Totally eight distinct haplotypes of exon 2 were obtained in four individuals. With-in 237 bp nucleotide sequences from four samples, 30 vari-able positions were found, and 21 putative peptide-binding positions were disclosed in 79 amino acid residues. The ratio of nonsynonymous substitutions (dN) was much higher than that of synonymous substitutions (dS), which indicated that balancing selection probably maintain the variation ofexon 2. MEGA neighbor joining (N J) and PAUP maximum parsimo-ny (MP) methods were used to reconstruct phylogenetic trees among species, respectively. Results displayed a more close relationship between leopard and tiger; however, clouded leopard has a comparatively distant relationship form the other two.     

Divergent patterns of selection on the DAB and DXB MHC class II loci in Xiphophorus fishes

Two MHC class II loci, DAB (a classical class II locus) and DXB (putatively a non-classical class II locus), were sequenced in samples of individuals from two populations of swordtail fish, Xiphophorus multilineatus and X. pygmaeus. The DAB locus showed higher levels of genetic variation in the B1-encoding region, (putative binding region) than the DXB locus. We used two methods to investigate d_N/d_S ratios. The results from a maximum likelihood method based on phylogenetic relationships indicated positive selection on the B1 region of DAB (this method could not be used on DXB). Results from a coalescent-based method also showed evidence for positive selection in the B1 region of DAB, but only weak evidence for selection on the DXB. Further analyses indicated that recombination is an important source of variation in the B1 region of DAB, but has a relatively small effect on DXB. Overall, our results were consistent with the hypothesis that the DAB locus is under positive selection driven by antagonistic coevolution, and that the DXB locus plays the role of a non-classical MHC II locus. We also used simulations to investigate the presence of an elevated synonymous substitution rate in the binding region. The simulations revealed that the elevated rate could be caused by an interaction between positive selection and codon bias. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

MHC-based mate choice combines good genes and maintenance of MHC polymorphism

Polymorphic genes of the major histocompatibility complex (MHC) are regarded as essential genes for individual fitness under conditions of natural and sexual selection. To test this hypothesis, we investigated the ultimate individual fitness trait — that of reproductive success. We used three-spined sticklebacks ( Gasterosteus aculeatus ) in seminatural enclosures, located in natural breeding areas where the experimental fish had been caught. During their reproductive period, fish were exposed continuously to their natural sympatric parasites. By genotyping almost 4000 eggs with nine microsatellites, we determined parenthood and inferred female mating decision. We found that with reference to their own MHC profile, female sticklebacks preferred to mate with males sharing an intermediate MHC diversity. In addition, males with a specific MHC haplotype were bigger and better at fighting a common parasite ( Gyrodactylus sp.). This translated directly into Darwinian fitness since fish harbouring this specific MHC haplotype were more likely to be chosen and had a higher reproductive output. We conclude that females also based their mating decision on a specific MHC haplotype conferring resistance against a common parasite. This identifies and supports 'good genes'. We argue that such an interaction between host and parasite driving assortative mating is not only a prerequisite for negative frequency-dependent selection — a potential mechanism to explain the maintenance of MHC polymorphism, but also potentially speciation.     

Complete loss of MHC genetic diversity in the Common Hamster (Cricetus cricetus) population in The Netherlands. Consequences for conservation strategies

The Common Hamster (Cricetus cricetus L.)has suffered from changes in agriculturalpractices. In some Western European countriesthe populations have become so small andscattered that they are threatened withextinction. We studied the genetic diversity ofmitochondrial and major histoincompatibilitycomplex (MHC) loci in the few animals left inthe South of the Netherlands and in threeanimals from the Alsace region in France, andcompared it to the diversity in Dutch animalsin the past (samples taken from stuffed animalsin museum collections dating back to the period1924–1956) and in a large present-daypopulation from Czech Republic. For themitochondrial cytochrome b gene, SNP mappingdemonstrated a total of nine alleles among 14Czech samples, of which one (possibly two) waspresent in the Dutch museum samples, and onlyone in the current Dutch animals. For the MHCgenes, DQA exon 2 and 3 showed no variation,while 14 different alleles were found at DRBexon 2. The Czech population contained 13different alleles in 15 animals sampled, andmost animals were heterozygous (H_o = 0.80,H_e = 0.91). Therefore, the solitary livingHamster maintains, in nature, a large diversityat this MHC locus. The Dutch museum samplescontained eight different alleles in 20 samples, and they were slightly less heterozygous (H_o = 0.60, H_e = 0.75). All but one ofthese alleles were also found in the Czechsamples. In contrast, the present Dutch andFrench animals (a total of 16 samples)contained only one of these alleles, and allanimals were genetically identical andhomozygous. We conclude that the remaininganimals have lost all diversity at this MHClocus. This is probably the result of a severebottleneck, which may have been quite severe,reducing diversity in many loci. In addition,the remaining Dutch animals are partly derivedfrom one family. These animals are now part ofa breeding program. Options for restocking thegenetic diversity are discussed.     

Historical and contemporary selection of teleost MHC genes: did we leave the past behind?

The extreme polymorphism of antigen‐presenting genes of the major histocompatibility complex (MHC) has spurred intense research unparalleled for any other gene family. This applies also to teleosts where sequence information is available for 3559 MHC class I and class II allelic variants from 137 species. This review summarizes current knowledge on the origin and maintenance of diversity at classical MHC loci. Most studies identified positive selection (i.e. elevated rates of non‐synonymous over synonymous substitutions, dN/dS) as a sign of balancing selection. A meta‐analysis on nine species with sufficient numbers of class I and class II sequences revealed that recombination rate and intensity of positive selection were positively correlated, suggesting that recombination and gene conversion played a significant role in shaping the allelic repertoire. Processes that create diversity over long timescales need to be complemented by contemporary balancing selection, either through overdominance or frequency‐dependent selection, in order to explain the high allelic diversity observed today. While some evidence for overdominance exists for a few taxa (mainly salmonids) by correlating parasite infection data or survival to MHC genotypes, field or experimental data on negative frequency‐dependent selection are lacking altogether, even though some fish species are particularly suitable as model systems. Theoretical predictions suggest that negative frequency‐dependent selection is necessary to maintain the existing polymorphism. Hence, future empirical studies should focus on detecting signals that differentiate between mechanisms of contemporary selection rather than repeatedly showing historical selection events.     

家禽主要组织相容性复合体的研究进展

随着家禽基因组计划的开展,对家禽的主要组织相容性复合体（MHC）的研究取得了较大的进展。关于家禽MHC的各部分基因研究正在逐步深入,并且完成了MHC部分测序和染色体定位工作。 本文介绍近些年来对家禽MHC的基因结构和作用、与抗体的作用以及相关的基因组研究所取得的进展。人、小鼠及其他动物的相关研究结果将对家禽MHC研究的发展产生重要的影响。Abstract:As the development of poultry genome project,it has been acquired many advances in the study of poultry MHC.At present,we have achieved some MHC sequences 、 locations of MHC on chromosome and some MHC gene functions.This article give a detailed introduction about gene structure of poultry MHC and its role in immune reaction、relation with antibody and advances in poultry genome about MHC.With the development of related research,how to use the result of the study more efficiently become more and more important to the poultry MHC study.     

Mate preferences and infectious disease: theoretical considerations and evidence in humans

Mate preferences may operate in part to mitigate the threats posed by infectious disease. In this paper, we outline various ways in which preferring healthy mates can offer direct benefits in terms of pathogen avoidance and indirect benefits in terms of heritable immunity to offspring, as well as the costs that may constrain mate preferences for health. We then pay special attention to empirical work on mate preferences in humans given the depth and breadth of research on human mating. We review this literature and comment on the degree to which human mate preferences may reflect preferences for health.     

A comparison of variability and population structure for major histocompatibility complex and microsatellite loci in California coastal steelhead (Oncorhynchus mykiss Walbaum)

The major histocompatibility complex (MHC) contains genes integral to immune response in vertebrates. MHC genes have been shown to be under selection in a number of vertebrate taxa, making them intriguing for population genetic studies. We have conducted a survey of genetic variation in an MHC class II gene for steelhead trout from 24 sites in coastal California and compared this variation to that observed at 16 presumably neutral microsatellite loci. A high amount of allelic variation was observed at the MHC when compared to previously published studies on other Pacific salmonids. Elevated nonsynonymous substitutions, relative to synonymous substitutions, were detected at the MHC gene, indicating the signature of historical balancing selection. The MHC data were tested for correlations to and deviations from the patterns found with the microsatellite data. Estimates of allelic richness for the MHC gene and for the microsatellites were positively correlated, as were estimates of population differentiation (F(ST)). An analysis for F(ST) outliers indicates that the MHC locus has an elevated F(ST) relative to the neutral expectation, although a significant result was found for only one particular geographical subgroup. Relatively uniform allele frequency distributions were detected in four populations, although this finding may be partially due to recent population bottlenecks. These results indicate that, at the scale studied here, drift and migration play a major role in the observed geographical variability of MHC genes in steelhead, and that contemporary selection is relatively weak and difficult to detect.     

Sexual selection explains more functional variation in the mammalian major histocompatibility complex than parasitism

Understanding drivers of genetic diversity at the major histocompatibility complex (MHC) is vitally important for predicting how vertebrate immune defence might respond to future selection pressures and for preserving immunogenetic diversity in declining populations. Parasite-mediated selection is believed to be the major selective force generating MHC polymorphism, and while MHC-based mating preferences also exist for multiple species including humans, the general importance of mate choice is debated. To investigate the contributions of parasitism and sexual selection in explaining among-species variation in MHC diversity, we applied comparative methods and meta-analysis across 112 mammal species, including carnivores, bats, primates, rodents and ungulates. We tested whether MHC diversity increased with parasite richness and relative testes size (as an indicator of the potential for mate choice), while controlling for phylogenetic autocorrelation, neutral mutation rate and confounding ecological variables. We found that MHC nucleotide diversity increased with parasite richness for bats and ungulates but decreased with parasite richness for carnivores. By contrast, nucleotide diversity increased with relative testes size for all taxa. This study provides support for both parasite-mediated and sexual selection in shaping functional MHC polymorphism across mammals, and importantly, suggests that sexual selection could have a more general role than previously thought.     

Cryptic preference for MHC-dissimilar females in male red junglefowl,Gallus gallus

An increasing number of studies test the idea that females increase offspring fitness by biasing fertilization in favour of genetically compatible partners; however, few have investigated or controlled for corresponding preferences in males. Here, we experimentally test whether male red junglefowl, Gallus gallus, prefer genetically compatible females, measured by similarity at the major histocompatibility complex (MHC), a key gene complex in vertebrate immune function. Theory predicts that because some degree of MHC heterozygosity favours viability, individuals should prefer partners that carry MHC alleles different from their own. While male fowl showed no preference when simultaneously presented with an MHC-similar and an MHC-dissimilar female, they showed a ‘cryptic’ preference, by allocating more sperm to the most MHC-dissimilar of two sequentially presented females. These results provide the first experimental evidence that males might respond to the MHC similarity of a female through differential ejaculate expenditure. By revealing that cryptic male behaviours may bias fertilization success in favour of genetically compatible partners, this study demonstrates the need to experimentally disentangle male and female effects when studying preferences for genetically compatible partners.     

A comparison of lymphocyte antigen specificities in Norwegian and Swiss goats

Summary. In all, 363 alloantireagents were tested in Berne, Switzerland and in Oslo, Norway against lymphocytes from 1679 goats of different breeds. The same lymphocytotoxicity test was used at both laboratories. The test data were pooled, and correlation coefficients for pairs of sera were used to group the sera in clusters. Twelve clusters were accepted as defining lymphocyte antigen specificities believed to be coded by genes within the major histocompatibility complex (MHC). The specificities defined by these clusters were designated Eu 1-Eu12. Two clusters defined specificities which were not coded from loci within the MHC. These were designated GLY-1.1 and GLY-2.1, and the loci GLY-1 and GLY-2, respectively. GLY-1.1 was also located on erythrocytes.