Home About us Contact
|
Home About us Contact | ||
|
|
||
MHC Loci (mhc + locus)
Selected AbstractsPATHOGEN RESISTANCE AND GENETIC VARIATION AT MHC LOCIEVOLUTION, Issue 10 2002Philip W. Hedrick Abstract., Balancing selection in the form of heterozygote advantage, frequency-dependent selection, or selection that varies in time and/or space, has been proposed to explain the high variation at major histocompatibility complex (MHC) genes. Here the effect of variation of the presence and absence of pathogens over time on genetic variation at multiallelic loci is examined. In the basic model, resistance to each pathogen is conferred by a given allele, and this allele is assumed to be dominant. Given that s is the selective disadvantage for homozygotes (and heterozygotes) without the resistance allele and the proportion of generations, which a pathogen is present, is e, fitnesses for homozygotes become (1 ,s)(n-1)e and the fitnesses for heterozygotes become (1 ,s)(n-2)e, where n is the number of alleles. In this situation, the conditions for a stable, multiallelic polymorphism are met even though there is no intrinsic heterozygote advantage. The distribution of allele frequencies and consequently heterozygosity are a function of the autocorrelation of the presence of the pathogen in subsequent generations. When there is a positive autocorrelation over generations, the observed heterozygosity is reduced. In addition, the effects of lower levels of selection and dominance and the influence of genetic drift were examined. These effects were compared to the observed heterozygosity for two MHC genes in several South American Indian samples. Overall, resistance conferred by specific alleles to temporally variable pathogens may contribute to the observed polymorphism at MHC genes and other similar host defense loci. [source] Between-year variation of MHC allele frequencies in great reed warblers: selection or drift?JOURNAL OF EVOLUTIONARY BIOLOGY, Issue 3 2004H. Westerdahl Abstract The major histocompatibility complex (MHC) genes are extremely polymorphic and this variation is assumed to be maintained by balancing selection. Cyclic interactions between pathogens and their hosts could generate such selection, and specific MHC alleles or heterozygosity at certain MHC loci have been shown to confer resistance against particular pathogens. Here we compare the temporal variation in allele frequencies of 23 MHC class I alleles with that of 23 neutral microsatellite markers in adult great reed warblers (a passerine bird) in nine successive cohorts. Overall, the MHC alleles showed a significantly higher variation in allele frequencies between cohorts than the microsatellite alleles, using a multi-variate genetic analysis (amova). The frequency of two specific MHC alleles, A3e (P = 0.046) and B4b (P = 0.0018), varied more between cohorts than expected from random, whereas none of the microsatellite alleles showed fluctuations exceeding the expectation from stochastic variation. These results imply that the variation in MHC allele frequencies between cohorts is not a result of demographic events, but rather an effect of selection favouring different MHC alleles in different years. [source] Spatio-temporal variation in the strength and mode of selection acting on major histocompatibility complex diversity in water vole (Arvicola terrestris) metapopulationsMOLECULAR ECOLOGY, Issue 1 2009MATTHEW K. OLIVER Abstract Patterns of spatio-temporal genetic variation at a class II major histocompatibility complex (MHC) locus and multiple microsatellite loci were analysed within and between three water vole metapopulations in Scotland, UK. Comparisons of MHC and microsatellite spatial genetic differentiation, based on standardised tests between two demographically asynchronous zones within a metapopulation, suggested that spatial MHC variation was affected by balancing selection, directional selection and random genetic drift, but that the relative effects of these microevolutionary forces vary temporally. At the metapopulation level, between-year differentiation for MHC loci was significantly correlated with that of microsatellites, signifying that neutral factors such as migration and drift were primarily responsible for overall temporal genetic change at the metapopulation scale. Between metapopulations, patterns of genetic differentiation implied that, at large spatial scales, MHC variation was primarily affected by directional selection and drift. Levels of MHC heterozygosity in excess of Hardy,Weinberg expectations were consistent with overdominant balancing selection operating on MHC variation within metapopulations. However, this effect was not constant among all samples, indicating temporal variation in the strength of selection relative to other factors. The results highlight the benefit of contrasting variation at MHC with neutral markers to separate the effects of stochastic and deterministic microevolutionary forces, and add to a growing body of evidence showing that the mode and relative strength of selection acting on MHC diversity varies both spatially and temporally. [source] MHC diversity and the association to nematode parasitism in the yellow-necked mouse (Apodemus flavicollis)MOLECULAR ECOLOGY, Issue 7 2005Y. MEYER-LUCHT Abstract In vertebrates, the genes of the major histocompatibility complex (MHC) are among the most debated candidates accounting for co-evolutionary processes of host,parasite interaction at the molecular level. The exceptionally high allelic polymorphism found in MHC loci is believed to be maintained by pathogen-driven selection, mediated either through heterozygous advantage or rare allele advantage (= frequency dependent selection). While investigations under natural conditions are still very rare, studies on humans or mice under laboratory conditions revealed support for both hypotheses. We investigated nematode burden and allelic diversity of a functional important MHC class II gene (DRB exon2) in free-ranging yellow-necked mice (Apodemus flavicollis). Twenty-seven distinct Apfl -DRB alleles were detected in 146 individuals with high levels of amino acid sequence divergence, especially at the antigen binding sites (ABS), indicating selection processes acting on this locus. Heterozygosity had no influence on the infection status (being infected or not), the number of different nematode infections (NNI) or the intensity of infection, measured as the individual faecal egg count (FEC). However, significant associations of specific Apfl -DRB alleles to both nematode susceptibility and resistance were found, for all nematodes as well as in separate analyses of the two most common nematodes. Apodemus flavicollis individuals carrying the alleles Apfl -DRB*5 or Apfl -DRB*15 revealed significantly higher FEC than individuals with other alleles. In contrast, the allele Apfl -DRB*23 showed a significant association to low FEC of the most common nematode. Thus, our results provide evidence for pathogen-driven selection acting through rare allele advantage under natural conditions. [source] Genetic drift outweighs balancing selection in shaping post-bottleneck major histocompatibility complex variation in New Zealand robins (Petroicidae)MOLECULAR ECOLOGY, Issue 12 2004HILARY C. MILLER Abstract The Chatham Island black robin, Petroica traversi, is a highly inbred, endangered passerine with extremely low levels of variation at hypervariable neutral DNA markers. In this study we investigated variation in major histocompatibility complex (MHC) class II genes in both the black robin and its nonendangered relative, the South Island robin Petroica australis australis. Previous studies have shown that Petroica have at least four expressed class II B MHC genes. In this study, the sequences of introns flanking exon 2 of these loci were characterized to design primers for peptide-binding region (PBR) sequence analysis. Intron sequences were comprised of varying numbers of repeated units, with highly conserved regions immediately flanking exon 2. Polymerase chain reaction primers designed to this region amplified three or four sequences per black robin individual, and eight to 14 sequences per South Island robin individual. MHC genes are fitness-related genes thought to be under balancing selection, so they may be more likely to retain variation in bottlenecked populations. To test this, we compared MHC variation in the black robin with artificially bottlenecked populations of South Island robin, and with their respective source populations, using restriction fragment length polymorphism analyses and DNA sequencing of the PBR. Our results indicate that the black robin is monomorphic at class II B MHC loci, while both source and bottlenecked populations of South Island robin have retained moderate levels of variation. Comparison of MHC variation with minisatellite DNA variation indicates that genetic drift outweighs balancing selection in determining MHC diversity in the bottlenecked populations. However, balancing selection appears to influence MHC diversity over evolutionary timescales, and the effects of gene conversion are evident. [source] Detection of arthritis-susceptibility loci, including Ncf1, and variable effects of the major histocompatibility complex region depending on genetic background in ratsARTHRITIS & RHEUMATISM, Issue 2 2009Carola Rintisch Objective To characterize the arthritis-modulating effects of 3 non,major histocompatibility complex (MHC) quantitative trait loci (QTLs) in rat experimental arthritis in the disease-resistant E3 strain, and to investigate the disease-modulating effects of the MHC region (RT1) in various genetic backgrounds. Methods A congenic fragment containing Ncf1 along with congenic fragments containing the strongest remaining loci, Pia5/Cia3 and Pia7/Cia13 on chromosome 4, were transferred from the arthritis-susceptible DA strain into the background of the completely resistant E3 strain. The arthritis-regulatory potential of the transferred alleles was evaluated by comparing the susceptibility to experimental arthritis in congenic rats with that in E3 rats. The RT1u haplotype from the E3 strain was transferred into the susceptible DA strain (RT1av1), and various F1 and F2 hybrids were generated to assess the effects of RT1 on arthritis susceptibility. Results The DA allele of Ncf1 did not break the arthritis resistance of the E3 rats, although it led to enhanced autoimmune B cell responses, as indicated by significantly elevated levels of anticollagen antibodies in congenic rats. Introgressing Pia5 and Pia7 loci on chromosome 4 broke the resistance to arthritis, and the MHC locus on chromosome 20 in DA rats enhanced arthritis when RT1 interacted with E3 genes. Conclusion The findings in these congenic lines confirm the existence of 3 major QTLs that regulate the severity of arthritis and are sufficient to induce the transformation of a completely arthritis-resistant rat strain into an arthritis-susceptible strain. This study also reveals a dramatic difference in the arthritis-regulatory potential of the rat MHC depending on genetic background, suggesting that strong epistatic interactions occur between MHC and non-MHC genes. [source] HLA,E gene polymorphism associated with susceptibility to kawasaki disease and formation of coronary artery aneurysmsARTHRITIS & RHEUMATISM, Issue 2 2009Y.-J. Lin Objective Kawasaki disease (KD) is a pediatric systemic vasculitis of unknown cause for which a genetic influence is supposed. The purpose of this study was to identify possible genetic variants in the major histocompatibility complex (MHC) region that are associated with KD and the development of coronary artery aneurysms (CAAs) in a Taiwanese population. Methods The 168 genetic variants covering the MHC locus were analyzed in an association study of a Taiwanese cohort of 93 KD patients and 680 unrelated healthy children matched for sex and age with the study patients. Results Eleven single-nucleotide polymorphisms (SNPs) were associated with the occurrence of KD. The SNP located at the 3,-untranslated region of HLA,E (rs2844724) was highly associated (P < 1 × 10,7). In addition, the frequency of the C allele was higher in KD patients without CAAs than in controls (P < 0.001) due to a significantly increased frequency of the CC and CT genotypes. Plasma levels of soluble HLA,E were significantly higher in KD patients than in controls regardless of the presence of CAAs. Furthermore, there was a trend toward higher plasma levels of soluble HLA,E in KD patients with the CT and TT genotypes of the HLA,E gene polymorphism. Conclusion Our results suggest that the HLA,E gene polymorphism may play a role in the pathogenesis of KD. [source] A Fundamental Problem with Amino-Acid-Sequence Characters for Phylogenetic AnalysesCLADISTICS, Issue 3 2000Mark P. Simmons Protein-coding genes may be analyzed in phylogenetic analyses using nucleotide-sequence characters and/or amino-acid-sequence characters. Although amino-acid-sequence characters "correct" for saturation (parallelism), amino-acid-sequence characters are subject to convergence and ignore phylogenetically informative variation. When all nucleotide-sequence characters have a consistency index of 1, characters coded using the amino acid sequence may have a consistency index of less than 1. The reason for this is that most amino acids are specified by more than one codon. If two different codons that both code for the same amino acid are derived independent of one another in divergent lineages, nucleotide-sequence characters may not be homoplasious when amino-acid-sequence characters may be homoplasious. Not only may amino-acid-sequence characters support groupings that are not supported by nucleotide-sequence characters, they may support contradictory groupings. Because this convergence is a problem of character delimitation, it affects the results of all tree-construction methods (maximum likelihood, neighbor joining, parsimony, etc.). In effect, coding amino-acid-sequence characters instead of nucleotide-sequence characters putatively corrects for saturation and definitely causes a convergence problem. An empirical example from the Mhc locus is given. [source] | ||||||||||||||||||||||