scholarly journals Maintaining functional major histocompatibility complex diversity under inbreeding: the case of a selfing vertebrate

2012 ◽  
Vol 279 (1749) ◽  
pp. 5004-5013 ◽  
Author(s):  
A. Ellison ◽  
J. Allainguillaume ◽  
S. Girdwood ◽  
J. Pachebat ◽  
K. M. Peat ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Adaptive Immune Response ◽  
Selective Advantage ◽  
Pathogen Resistance ◽  
Mixed Mating ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Genome Wide ◽  
Laboratory Populations ◽  
Mhc Diversity

Major histocompatibility complex (MHC) genes encode proteins that present pathogen-derived antigens to T-cells, initiating the adaptive immune response in vertebrates. Although populations with low MHC diversity tend to be more susceptible to pathogens, some bottlenecked populations persist and even increase in numbers despite low MHC diversity. Thus, the relative importance of MHC diversity versus genome-wide variability for the long-term viability of populations after bottlenecks and/or under high inbreeding is controversial. We tested the hypothesis that genome-wide inbreeding (estimated using microsatellites) should be more critical than MHC diversity alone in determining pathogen resistance in the self-fertilizing fish Kryptolebias marmoratus by analysing MHC diversity and parasite loads in natural and laboratory populations with different degrees of inbreeding. Both MHC and neutral diversities were lost after several generations of selfing, but we also found evidence of parasite selection acting on MHC diversity and of non-random loss of alleles, suggesting a possible selective advantage of those individuals with functionally divergent MHC, in accordance with the hypothesis of divergent allele advantage. Moreover, we found that parasite loads were better explained by including MHC diversity in the model than by genome-wide (microsatellites) heterozygosity alone. Our results suggest that immune-related overdominance could be the key in maintaining variables rates of selfing and outcrossing in K. marmoratus and other mixed-mating species.

scholarly journals Does intra-individual major histocompatibility complex diversity keep a golden mean?

2008 ◽  
Vol 364 (1513) ◽  
pp. 117-128 ◽  
Author(s):  
Benno Woelfing ◽  
Arne Traulsen ◽  
Manfred Milinski ◽  
Thomas Boehm
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
Adaptive Immune Response ◽  
Population Level ◽  
Current Data ◽  
Small Subset ◽  
Major Histocompatibility ◽  
Mhc Molecules ◽  
Histocompatibility Complex ◽  
Mhc Diversity

An adaptive immune response is usually initiated only if a major histocompatibility complex (MHC) molecule presents pathogen-derived peptides to T-cells. Every MHC molecule can present only peptides that match its peptide-binding groove. Thus, it seems advantageous for an individual to express many different MHC molecules to be able to resist many different pathogens. However, although MHC genes are the most polymorphic genes of vertebrates, each individual has only a very small subset of the diversity at the population level. This is an evolutionary paradox. We provide an overview of the current data on infection studies and mate-choice experiments and conclude that overall evidence suggests that intermediate intra-individual MHC diversity is optimal. Selective forces that may set an upper limit to intra-individual MHC diversity are discussed. An updated mathematical model based on recent findings on T-cell selection can predict the natural range of intra-individual MHC diversity. Thus, the aim of our review is to evaluate whether the number of MHC alleles usually present in individuals may be optimal to balance the advantages of presenting an increased range of peptides versus the disadvantages of an increased loss of T-cells.

scholarly journals Low major histocompatibility complex diversity in the Tasmanian devil predates European settlement and may explain susceptibility to disease epidemics

2013 ◽  
Vol 9 (1) ◽  
pp. 20120900 ◽  
Author(s):  
Katrina Morris ◽  
Jeremy J. Austin ◽  
Katherine Belov
Keyword(s):  
Major Histocompatibility Complex ◽  
Tasmanian Devil ◽  
Major Histocompatibility ◽  
European Settlement ◽  
Low Genetic Diversity ◽  
Histocompatibility Complex ◽  
Devil Facial Tumour Disease ◽  
History Of ◽  
Mhc Diversity ◽  
Disease Epidemics

The Tasmanian devil ( Sarcophilus harrisii ) is at risk of extinction owing to the emergence of a contagious cancer known as devil facial tumour disease (DFTD). The emergence and spread of DFTD has been linked to low genetic diversity in the major histocompatibility complex (MHC). We examined MHC diversity in historical and ancient devils to determine whether loss of diversity is recent or predates European settlement in Australia. Our results reveal no additional diversity in historical Tasmanian samples. Mainland devils had common modern variants plus six new variants that are highly similar to existing alleles. We conclude that low MHC diversity has been a feature of devil populations since at least the Mid-Holocene and could explain their tumultuous history of population crashes.

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

2013 ◽  
Vol 280 (1769) ◽  
pp. 20131605 ◽  
Author(s):  
J. C. Winternitz ◽  
S. G. Minchey ◽  
L. Z. Garamszegi ◽  
S. Huang ◽  
P. R. Stephens ◽  
...  
Keyword(s):  
Sexual Selection ◽  
Major Histocompatibility Complex ◽  
Mate Choice ◽  
Nucleotide Diversity ◽  
Major Histocompatibility ◽  
Parasite Richness ◽  
Histocompatibility Complex ◽  
Mhc Polymorphism ◽  
Testes Size ◽  
Mhc Diversity

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.

scholarly journals Comprehensive analysis of the major histocompatibility complex in systemic sclerosis identifies differential HLA associations by clinical and serological subtypes

2021 ◽  
pp. annrheumdis-2021-219884
Author(s):  
Marialbert Acosta-Herrera ◽  
Martin Kerick ◽  
Elena Lopéz-Isac ◽  
Shervin Assassi ◽  
Lorenzo Beretta ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Systemic Sclerosis ◽  
Genome Wide Association Study ◽  
Genetic Effect ◽  
Nucleotide Polymorphisms ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Genome Wide ◽  
Novel Association ◽  
Hla Dqa1

ObjectiveThe greatest genetic effect reported for systemic sclerosis (SSc) lies in the major histocompatibility complex (MHC) locus. Leveraging the largest SSc genome-wide association study, we aimed to fine-map this region to identify novel human leucocyte antigen (HLA) genetic variants associated with SSc susceptibility and its main clinical and serological subtypes.Methods9095 patients with SSc and 17 584 controls genome-wide genotyped were used to impute and test single-nucleotide polymorphisms (SNPs) across the MHC, classical HLA alleles and their composite amino acid residues. Additionally, patients were stratified according to their clinical and serological status, namely, limited cutaneous systemic sclerosis (lcSSc), diffuse cutaneous systemic sclerosis (dcSSc), anticentromere (ACA), antitopoisomerase (ATA) and anti-RNApolIII autoantibodies (ARA).ResultsSequential conditional analyses showed nine SNPs, nine classical alleles and seven amino acids that modelled the observed associations with SSc. This confirmed previously reported associations with HLA-DRB1*11:04 and HLA-DPB1*13:01, and revealed a novel association of HLA-B*08:01. Stratified analyses showed specific associations of HLA-DQA1*02:01 with lcSSc, and an exclusive association of HLA-DQA1*05:01 with dcSSc. Similarly, private associations were detected in HLA-DRB1*08:01 and confirmed the previously reported association of HLA-DRB1*07:01 with ACA-positive patients, as opposed to the HLA-DPA1*02:01 and HLA-DQB1*03:01 alleles associated with ATA presentation.ConclusionsThis study confirms the contribution of HLA class II and reveals a novel association of HLA class I with SSc, suggesting novel pathways of disease pathogenesis. Furthermore, we describe specific HLA associations with SSc clinical and serological subtypes that could serve as biomarkers of disease severity and progression.

scholarly journals Costly major histocompatibility complex signals produced only by reproductively active males, but not females, must be validated by a ‘maleness signal’ in three-spined sticklebacks

2009 ◽  
Vol 277 (1680) ◽  
pp. 391-398 ◽  
Author(s):  
Manfred Milinski ◽  
Siân W. Griffiths ◽  
Thorsten B. H. Reusch ◽  
Thomas Boehm
Keyword(s):  
Major Histocompatibility Complex ◽  
Mate Choice ◽  
Immune Function ◽  
Major Histocompatibility ◽  
Reproductive State ◽  
Complex Signals ◽  
Olfactory Information ◽  
Histocompatibility Complex ◽  
Mhc Diversity ◽  
Gravid Females

Olfactory information about individual major histocompatibility complex (MHC) immune genotypes is important for mate choice in several species. For example, during the mate choice decisions of three-spined sticklebacks, females assess males on the basis of odour cues that convey information about their MHC diversity. Here, we show that an additional ‘maleness’ signal is needed to validate the MHC signal. Furthermore, using interaction between natural odour of sticklebacks and synthetic MHC-ligand peptides, we show that MHC signals are conditional on the reproductive state in males. By contrast, we find that gravid females do not produce such signals. Since MHC olfactory signals relevant to mate choice decisions are conditional upon gender and reproductive state, we suggest that their manufacture is likely to be costly to senders, and therefore, potentially conditional on the health/parasitization status of the sender. We hypothesize that shedding of peptide–MHC complexes compromises immune function, selecting against unconditional use of these signals.

scholarly journals Birdsong signals individual diversity at the major histocompatibility complex

2017 ◽  
Vol 13 (11) ◽  
pp. 20170430 ◽  
Author(s):  
J. W. G. Slade ◽  
M. J. Watson ◽  
E. A. MacDougall-Shackleton
Keyword(s):  
Major Histocompatibility Complex ◽  
Early Life ◽  
Major Histocompatibility ◽  
Song Repertoire ◽  
Song Complexity ◽  
Song Sparrows ◽  
Histocompatibility Complex ◽  
Trade Offs ◽  
Material Benefits ◽  
Mhc Diversity

The major histocompatibility complex (MHC) plays a key role in vertebrate immunity, and pathogen-mediated selection often favours certain allelic combinations. Assessing potential mates' MHC profiles may provide receivers with genetic benefits (identifying MHC-compatible mates and producing optimally diverse offspring) and/or material benefits (identifying optimally diverse mates capable of high parental investment). Oscine songbirds learn songs during early life, such that song repertoire content can reflect population of origin while song complexity can reflect early life condition. Thus birdsong may advertise the singer's genetic dissimilarity to others in the population (and, presumably, compatibility with potential mates), or individual genetic diversity (and thus condition-dependent material benefits). We tested whether song repertoire content and/or complexity signal MHC class IIβ dissimilarity and/or diversity in male song sparrows ( Melospiza melodia ). Pairwise dissimilarity in repertoire content did not predict MHC dissimilarity between males, suggesting that locally rare songs do not signal rare MHC profiles. Thus, geographical variation in song may not facilitate MHC-mediated inbreeding or outbreeding. Larger repertoires were associated with intermediate MHC diversity, suggesting intermediate rather than maximal MHC diversity is optimal. This could reflect trade-offs between resisting infection and autoimmune disorders. Song complexity may advertise optimal MHC diversity, a trait affecting disease resistance and capacity for parental care.

scholarly journals Lifetime reproductive success is maximized with optimal major histocompatibility complex diversity

2008 ◽  
Vol 276 (1658) ◽  
pp. 925-934 ◽  
Author(s):  
Martin Kalbe ◽  
Christophe Eizaguirre ◽  
Ilka Dankert ◽  
Thorsten B.H Reusch ◽  
Ralf D Sommerfeld ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Reproductive Success ◽  
Mhc Class Ii ◽  
Gasterosteus Aculeatus ◽  
Natural Populations ◽  
Lifetime Reproductive Success ◽  
Breeding Period ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Mhc Diversity

Individual diversity at the major histocompatibility complex (MHC) is predicted to be optimal at intermediate rather than at maximal levels. We showed previously in sticklebacks that an intermediate MHC diversity is predominant in natural populations and provides maximal resistance in experimental multiple parasite infections in the laboratory. However, what counts ultimately is the lifetime reproductive success (LRS). Here, we measured LRS of six laboratory-bred sib-groups—to minimize the influence of non-MHC genes—three-spined sticklebacks ( Gasterosteus aculeatus ) during their entire breeding period, each in a seminatural enclosure in the lake of their parents, where they were exposed to the natural spectrum of parasites. We collected developing clutches at regular intervals and determined parenthood for a representative number of eggs (2279 in total) per clutch with 18 microsatellites. Both males and females with an intermediate MHC class II B variant number had the highest LRS. The mechanistic link of MHC diversity and LRS differed between the sexes: in females, we found evidence for a trade-off between number of eggs and immunocompentence, whereas in males this correlation was concealed by different timing strategies of reproduction.

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