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Biomedical subjects

K Mathias Wegner

Publications and source records attributed to K Mathias Wegner.

5 recordsLinked to original sources
PubMed2005

Mate choice decisions of stickleback females predictably modified by MHC peptide ligands.

Sexual selection has been proposed as one mechanism to explain the maintenance of high allelic diversity in MHC genes that control the extent of resistance against pathogens and parasites in natural populations. MHC-based sexual selection is known to involve olfactory mechanisms in fish, mice, and humans. During mate choice, females of the three-spined stickleback (Gasterosteus aculeatus) use an odor-based selection strategy to achieve an optimal level of MHC diversity in their offspring, equipping them with optimal resistance toward pathogens and parasites. The molecular mechanism of odor-based mate-selection strategies is unknown. Because peptide ligands for MHC class I molecules function as individuality signals in mice, we hypothesized that female sticklebacks might assess the degree of MHC diversity of potential partners by means of the structural diversity of the corresponding peptide ligands in perceived odor signals. We show that structurally diverse MHC ligands interact with natural odors of male sticklebacks to predictably modify MHC-related mate choice. For a mating pair with suboptimal numbers of MHC alleles, peptides increase the attractiveness of male water, whereas for a mating pair with superoptimal numbers, attractiveness is decreased. Our results suggest that female sticklebacks use evolutionarily conserved structural features of MHC peptide ligands to evaluate MHC diversity of their prospective mating partners.

Amino Acid Sequence↗
PubMed2004

Recent duplication and inter-locus gene conversion in major histocompatibility class II genes in a teleost, the three-spined stickleback.

Using a bacterial artificial chromosome (BAC) library, we analysed a 99.5 kb genomic segment containing the major histocompatibility class II genes of a teleost, the three-spined stickleback Gasterosteus aculeatus. Experiments with G. aculeatus have provided direct evidence for balancing selection by pathogens and mate choice driving MH class II beta polymorphism. Two sets of paralogous class II alpha genes and beta genes in a tandem arrangement were identified, designated Gaac-DAA/DAB and Gaac-DBA/DBB. Expression analysis of the beta genes using single-strand conformation polymorphism revealed that both gene copies are expressed. Based on an analysis of pairwise nucleotide polymorphisms, we estimate that the duplication into two paralogous class II loci occurred only 1.2-2.4 million years ago, 1-2 orders of magnitude more recently than in other fish, bird or mammalian species. At the 3'-direction of the classical MH loci, we identified another seven genes or gene fragments, two of which (small inducible cytokine, complement regulatory factor) are related to immune function in other vertebrates. None of these genes were associated with MH class II genes in zebrafish, suggesting a markedly different organisation of the MH class II region in sticklebacks, and presumably, across bony fishes. When the nucleotide substitution pattern of the novel class II beta genes was analysed together with a representative sequence sample isolated from fish in northern Germany (n=27), we found that the peptide binding region of the Gaac-DAB and Gaac-DBB loci had undergone an inter-locus gene conversion (P=0.007). In accordance, we found a 10- to 20-fold higher frequency of CpG-islands on the MH class II segment compared to other species, a feature that may be conducive for inter-locus recombination.

Amino Acid Sequence↗
PubMed2004

Major histocompatibility complex diversity influences parasite resistance and innate immunity in sticklebacks.

Proteins of the major histocompatibility complex (MHC) play a central role in the presentation of antigens to the adaptive immune system. The MHC also influences the odour-based choice of mates in humans and several animal taxa. It has recently been shown that female three-spined sticklebacks (Gasterosteus aculeatus) aim at a moderately high MHC diversity in their offspring when choosing a mate. Do they optimize the immune systems of their offspring? Using three-spined sticklebacks that varied in their individual numbers of MHC class IIB molecules, we tested, experimentally, whether allelic diversity at the MHC influences parasite resistance and immune parameters. We found that sticklebacks with low MHC diversity suffered more from parasite infection after experimental exposure to Schistocephalus solidus tapeworms and Glugea anomala microsporidians. They also showed the highest proportion of granulocytes and the strongest respiratory burst reaction, which are correlates of innate immunity. This indicates a strong activity of the innate immune system after challenge by parasites when MHC diversity is suboptimal. Individuals with very high allelic diversity at the MHC seemed inferior to those with moderately high diversity. Such a pattern is consistent with theoretical expectations of an optimal balance between the number of recognizable antigens and self-tolerance.

Alleles↗
PubMed2004

Parasites and individual major histocompatibility complex diversity--an optimal choice?

Overdominant selection or heterozygote advantage can partly explain the extraordinary polymorphism found at classical major histocompatibility complex (MHC) loci. However, several studies employing only single infectious agents often failed to detect it. Here, we review recent studies suggesting that due to the dominant nature of MHC-mediated resistance, a heterozygote advantage is most likely to be detected in multiple pathogen challenges.

Animals↗