Major Histocompatibility Complex Allele Frequencies Research Articles

Mechanisms governing avian phylosymbiosis: Genetic dissimilarity based on neutral and MHC regions exhibits little relationship with gut microbiome distributions of Galápagos mockingbirds.

The gut microbiome of animals, which serves important functions but can also contain potential pathogens, is to varying degrees under host genetic control. This can generate signals of phylosymbiosis, whereby gut microbiome composition matches host phylogenetic structure. However, the genetic mechanisms that generate phylosymbiosis and the scale at which they act remain unclear. Two non‐mutually exclusive hypotheses are that phylosymbiosis is driven by immunogenetic regions such as the major histocompatibility complex (MHC) controlling microbial composition, or by spatial structuring of neutral host genetic diversity via founder effects, genetic drift, or isolation by distance. Alternatively, associations between microbes and host phylogeny may be generated by their spatial autocorrelation across landscapes, rather than the direct effects of host genetics. In this study, we collected MHC, microsatellite, and gut microbiome data from separate individuals belonging to the Galápagos mockingbird species complex, which consists of four allopatrically distributed species. We applied multiple regression with distance matrices and Bayesian inference to test for correlations between average genetic and microbiome similarity across nine islands for which all three levels of data were available. Clustering of individuals by species was strongest when measured with microsatellite markers and weakest for gut microbiome distributions, with intermediate clustering of MHC allele frequencies. We found that while correlations between island‐averaged gut microbiome composition and both microsatellite and MHC dissimilarity existed across species, these relationships were greatly weakened when accounting for geographic distance. Overall, our study finds little support for large‐scale control of gut microbiome composition by neutral or adaptive genetic regions across closely related bird phylogenies, although this does not preclude the possibility that host genetics shapes gut microbiome at the individual level.

Balancing selection versus allele and supertype turnover in MHC class II genes in guppies.

Selection pressure from parasites is thought to be a major force shaping the extreme polymorphism of the major histocompatibility complex (MHC) genes, but the modes and consequences of selection remain unclear. Here, we analyse MHC class II and microsatellite diversity in 16 guppy (Poecilia reticulata) populations from two islands (Trinidad and Tobago) that have been separated for at least 10 ky. Within-population MHC diversity was high, but allele sharing was limited within islands and even lower between islands, suggesting relatively fast turnover of alleles. Allelic lineages strongly supported in phylogenetic analyses tended to be island-specific, suggesting rapid lineage sorting, and an expansion of an allelic lineage private to Tobago was observed. New alleles appear to be generated locally at a detectably high frequency. We did not detect a consistent signature of local adaptation, but FST outlier analysis suggested that balancing selection may be the more general process behind spatial variation in MHC allele frequencies in this system, particularly within Trinidad. We found no evidence for divergent allele advantage within populations, or for decreased genetic structuring of MHC supertypes compared to MHC alleles. The dynamic and complex nature of MHC evolution we observed in guppies, coupled with some evidence for balancing selection shaping MHC allele frequencies, are consistent with Red Queen processes of host-parasite coevolution.

High major histocompatibility complex class I polymorphism despite bottlenecks in wild and domesticated populations of the zebra finch (Taeniopygia guttata).

BackgroundTwo subspecies of zebra finch, Taeniopygia guttata castanotis and T. g. guttata are native to Australia and the Lesser Sunda Islands, respectively. The Australian subspecies has been domesticated and is now an important model system for research. Both the Lesser Sundan subspecies and domesticated Australian zebra finches have undergone population bottlenecks in their history, and previous analyses using neutral markers have reported reduced neutral genetic diversity in these populations. Here we characterize patterns of variation in the third exon of the highly variable major histocompatibility complex (MHC) class I α chain. As a benchmark for neutral divergence, we also report the first mitochondrial NADH dehydrogenase 2 (ND2) sequences in this important model system.ResultsDespite natural and human-mediated population bottlenecks, we find that high MHC class I polymorphism persists across all populations. As expected, we find higher levels of nucleotide diversity in the MHC locus relative to neutral loci, and strong evidence of positive selection acting on important residues forming the peptide-binding region (PBR). Clear population differentiation of MHC allele frequencies is also evident, and this may be due to adaptation to new habitats and associated pathogens and/or genetic drift. Whereas the MHC Class I locus shows broad haplotype sharing across populations, ND2 is the first locus surveyed to date to show reciprocal monophyly of the two subspecies.ConclusionsDespite genetic bottlenecks and genetic drift, all surveyed zebra finch populations have maintained high MHC Class I diversity. The diversity at the MHC Class I locus in the Lesser Sundan subspecies contrasts sharply with the lack of diversity in previously examined neutral loci, and may thus be a result of selection acting to maintain polymorphism. Given uncertainty in historical population demography, however, it is difficult to rule out neutral processes in maintaining the observed diversity. The surveyed populations also differ in MHC Class I allele frequencies, and future studies are needed to assess whether these changes result in functional immune differences.Electronic supplementary materialThe online version of this article (doi:10.1186/s12862-015-0546-3) contains supplementary material, which is available to authorized users.

Spatial patterns of neutral and functional genetic variations reveal patterns of local adaptation in raccoon (Procyon lotor) populations exposed to raccoon rabies

Local adaptation is necessary for population survival and depends on the interplay between responses to selective forces and demographic processes that introduce or retain adaptive and maladaptive attributes. Host-parasite systems are dynamic, varying in space and time, where both host and parasites must adapt to their ever-changing environment in order to survive. We investigated patterns of local adaptation in raccoon populations with varying temporal exposure to the raccoon rabies virus (RRV). RRV infects approximately 85% of the population when epizootic and has been presumed to be completely lethal once contracted; however, disease challenge experiments and varying spatial patterns of RRV spread suggest some level of immunity may exist. We first assessed patterns of local adaptation in raccoon populations along the eastern seaboard of North America by contrasting spatial patterns of neutral (microsatellite loci) and functional, major histocompatibility complex (MHC) genetic diversity and structure. We explored variation of MHC allele frequencies in the light of temporal population exposure to RRV (0-60 years) and specific RRV strains in infected raccoons. Our results revealed high levels of MHC variation (66 DRB exon 2 alleles) and pronounced genetic structure relative to neutral microsatellite loci, indicative of local adaptation. We found a positive association linking MHC genetic diversity and temporal RRV exposure, but no association with susceptibility and resistance to RRV strains. These results have implications for landscape epidemiology studies seeking to predict the spread of RRV and present an example of how population demographics influence the degree to which populations adapt to local selective pressures.

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

Maintaining effective immune response is an essential factor in the survival of small populations. One of the most important immune gene regions is the highly polymorphic major histocompatibility complex (MHC). We investigated how a population bottleneck and recovery have influenced the diversity and selection in three MHC class II loci, DLA-DRB1, DLA-DQA1 and DLA-DQB1, in the Finnish wolf population. We studied the larger Russian Karelian wolf population for comparison and used 17 microsatellite markers as reference loci. The Finnish and Karelian wolf populations did not differ substantially in their MHC diversities (GST″=0.047, P=0.377), but differed in neutral microsatellite diversities (GST″=0.148, P=0.008). MHC allele frequency distributions in the Finnish population were more even than expected under neutrality, implying balancing selection. In addition, an excess of nonsynonymous compared to synonymous polymorphisms indicated historical balancing selection. We also studied association between helminth (Trichinella spp. and Echinococcus canadensis) prevalence and MHC diversity at allele and SNP level. MHC-heterozygous wolves were less often infected by Trichinella spp. and carriers of specific MHC alleles, SNP haplotypes and SNP alleles had less helminth infections. The associated SNP haplotypes and alleles were shared by different MHC alleles, which emphasizes the necessity of single-nucleotide-level association studies also in MHC. Here, we show that strong balancing selection has had similar effect on MHC diversities in the Finnish and Russian Karelian wolf populations despite significant genetic differentiation at neutral markers and small population size in the Finnish population.

Donor population size rather than local adaptation can be a key determinant of amphibian translocation success

AbstractTranslocation of species to new locations is a widespread procedure in conservation biology. Conventional wisdom suggests using large numbers of donor stock from sites as close and as ecologically similar to the recipient location as possible to minimise risks from maladaptation and outbreeding depression. Here, we compare translocation success to a common receptor site of animals from a large but distant population with those from smaller proximal populations. Common toads (Bufo bufo) from a site far from the recipient locality and with very different habitat rapidly established a new population where three attempts with local animals failed. After 10 years, the new population retained allele frequency distributions at microsatellite loci almost the same as the donor site, whereas major histocompatibility complex allele frequencies changed to resemble local ones. Variations in phenology and climate could not readily explain the success of the distant translocation source. We postulate that success was due to the very large size of the donor population compared with local sources, implying that high levels of mean fitness or adaptive variation can be more important than local factors when considering translocations, at least in some circumstances.

Inference of Selection Based on Temporal Genetic Differentiation in the Study of Highly Polymorphic Multigene Families

The co-evolutionary arms race between host immune genes and parasite virulence genes is known as Red Queen dynamics. Temporal fluctuations in allele frequencies, or the ‘turnover’ of alleles at immune genes, are concordant with predictions of the Red Queen hypothesis. Such observations are often taken as evidence of host-parasite co-evolution. Here, we use computer simulations of the Major Histocompatibility Complex (MHC) of guppies (Poecilia reticulata) to study the turnover rate of alleles (temporal genetic differentiation, G'ST). Temporal fluctuations in MHC allele frequencies can be ≥≤order of magnitude larger than changes observed at neutral loci. Although such large fluctuations in the MHC are consistent with Red Queen dynamics, simulations show that other demographic and population genetic processes can account for this observation, these include: (1) overdominant selection, (2) fluctuating population size within a metapopulation, and (3) the number of novel MHC alleles introduced by immigrants when there are multiple duplicated genes. Synergy between these forces combined with migration rate and the effective population size can drive the rapid turnover in MHC alleles. We posit that rapid allelic turnover is an inherent property of highly polymorphic multigene families and that it cannot be taken as evidence of Red Queen dynamics. Furthermore, combining temporal samples in spatial FST outlier analysis may obscure the signal of selection.

Selection Maintains MHC Diversity through a Natural Population Bottleneck

A perceived consequence of a population bottleneck is the erosion of genetic diversity and concomitant reduction in individual fitness and evolutionary potential. Although reduced genetic variation associated with demographic perturbation has been amply demonstrated for neutral molecular markers, the effective management of genetic resources in natural populations is hindered by a lack of understanding of how adaptive genetic variation will respond to population fluctuations, given these are affected by selection as well as drift. Here, we demonstrate that selection counters drift to maintain polymorphism at a major histocompatibility complex (MHC) locus through a population bottleneck in an inbred island population of water voles. Before and after the bottleneck, MHC allele frequencies were close to balancing selection equilibrium but became skewed by drift when the population size was critically low. MHC heterozygosity generally conformed to Hardy-Weinberg expectations except in one generation during the population recovery where there was a significant excess of heterozygous genotypes, which simulations ascribed to strong differential MHC-dependent survival. Low allelic diversity and highly skewed frequency distributions at microsatellite loci indicated potent genetic drift due to a strong founder affect and/or previous population bottlenecks. This study is a real-time examination of the predictions of fundamental evolutionary theory in low genetic diversity situations. The findings highlight that conservation efforts to maintain the genetic health and evolutionary potential of natural populations should consider the genetic basis for fitness-related traits, and how such adaptive genetic diversity will vary in response to both the demographic fluctuations and the effects of selection.

Rapid and adaptive evolution of MHC genes under parasite selection in experimental vertebrate populations.

The genes of the major histocompatibility complex are the most polymorphic genes in vertebrates, with more than 1,000 alleles described in human populations. How this polymorphism is maintained, however, remains an evolutionary puzzle. Major histocompatibility complex genes have a crucial function in the adaptive immune system by presenting parasite-derived antigens to T lymphocytes. Because of this function, varying parasite-mediated selection has been proposed as a major evolutionary force for maintaining major histocompatibility complex polymorphism. A necessary prerequisite of such a balancing selection process is rapid major histocompatibility complex allele frequency shifts resulting from emerging selection by a specific parasite. Here we show in six experimental populations of sticklebacks, each exposed to one of two different parasites, that only those major histocompatibility complex alleles providing resistance to the respective specific parasite increased in frequency in the next host generation. This result demonstrates experimentally that varying parasite selection causes rapid adaptive evolutionary changes, thus facilitating the maintenance of major histocompatibility complex polymorphism.

Effects of contrasting demographic histories on selection at major histocompatibility complex loci in two sympatric species of tuco-tucos (Rodentia: Ctenomyidae)

bij_1358 260..277 To explore the impact of history on selection and genetic structure at functional loci, we compared patterns of major histocompatibility complex (MHC) variability in two sympatric species of ctenomyid rodents with different demographic backgrounds. Although Ctenomys talarum has experienced a stable demographic history, Ctenomys australis has undergone a recent demographic expansion. Accordingly, we predicted that MHC allele frequency distributions should be more skewed, differences between coding and noncoding regions should be less pronounced, and evidence of current selection on MHC loci should be reduced in C. australis relative to C. talarum. To test these predictions, we compared variation at the MHC class II DRB and DQA genes with that at multiple neutral markers, including DQA intron 2, the mitochondrial control region, and 8–12 microsatellite loci. These analyses supported the first two of our predictions but indicated that estimates of selection (based on w-values) were greater for C. australis. Further exploration of these data, however, revealed differences in the time frames over which selection appears to have acted on each species, with evidence of contemporary selection on MHC loci being limited to C. talarum. Collectively, these findings indicate that demographic history can substantially influence genetic structure at functional loci and that the effects of history on selection may be temporally complex and dynamic. © 2010 The Linnean Society of London, Biological Journal of the Linnean Society, 2010, 99, 260–277. ADDITIONAL KEYWORDS: Ctenomys australis – Ctenomys talarum – expansion – population.

MHC allele frequency distributions under parasite-driven selection: A simulation model

BackgroundThe extreme polymorphism that is observed in major histocompatibility complex (MHC) genes, which code for proteins involved in recognition of non-self oligopeptides, is thought to result from a pressure exerted by parasites because parasite antigens are more likely to be recognized by MHC heterozygotes (heterozygote advantage) and/or by rare MHC alleles (negative frequency-dependent selection). The Ewens-Watterson test (EW) is often used to detect selection acting on MHC genes over the recent history of a population. EW is based on the expectation that allele frequencies under balancing selection should be more even than under neutrality. We used computer simulations to investigate whether this expectation holds for selection exerted by parasites on host MHC genes under conditions of heterozygote advantage and negative frequency-dependent selection acting either simultaneously or separately.ResultsIn agreement with simple models of symmetrical overdominance, we found that heterozygote advantage acting alone in populations does, indeed, result in more even allele frequency distributions than expected under neutrality, and this is easily detectable by EW. However, under negative frequency-dependent selection, or under the joint action of negative frequency-dependent selection and heterozygote advantage, distributions of allele frequencies were less predictable: the majority of distributions were indistinguishable from neutral expectations, while the remaining runs resulted in either more even or more skewed distributions than under neutrality.ConclusionsOur results indicate that, as long as negative frequency-dependent selection is an important force maintaining MHC variation, the EW test has limited utility in detecting selection acting on these genes.

Major histocompatibility complex genes, symmetry, and body scent attractiveness in men and women

Previous research indicates that the scent of developmental stability (low fluctuating asymmetry, FA) is attractive to women who are fertile (at high-conception risk points in their menstrual cycles), but not to other women or men. Prior research also indicates that the scent of dissimilarity in major histocompatibility complex (MHC) genes may play a role in human mate choice. We studied the scent attractiveness to the opposite sex of t-shirts worn for 2 nights' sleep. Our results indicate that the two olfactory systems are independent. We repeated previous results from studies of the scent of symmetry. We repeated previous results from MHC research in part; men, but not women, showed a preference for t-shirts with the scent of MHC dissimilarity. Women's scent ratings of t-shirts were uncorrelated with the wearer's MHC dissimilarity and allele frequency, but positively correlated with the wearer's MHC heterozygosity. Fertile women did not exhibit any MHC trait preferences. Women's preference for the scent of men who were heterozygous for MHC alleles may be stronger in women who are at infertile cycle points. Men preferred the scent of common MHC alleles, which may function to avoid mates with rare alleles that exhibit gestational drive. Men also preferred the scent of women at fertile cycle points. The scent of facially attractive women, but not men, was preferred. Neither FA nor facial attractiveness in either sex correlated with MHC dissimilarity to others, MHC heterozygosity, or MHC allelic rarity. Copyright 2003.