Takahata N, Nei M.. Allelic genealogy under overdominant and frequency-dependent selection and polymorphism of major histocompatibility complex loci. Genetics 124: 967-978

Center for Demographic and Population Genetics, University of Texas Health Science Center, Houston 77225.
Genetics (Impact Factor: 5.96). 05/1990; 124(4):967-78.
Source: PubMed


To explain the long-term persistence of polymorphic alleles (trans-specific polymorphism) at the major histocompatibility complex (MHC) loci in rodents and primates, a computer simulation study was conducted about the coalescence time of different alleles sampled under various forms of selection. At the same time, average heterozygosity, the number of alleles in a sample, and the rate of codon substitution were examined to explain the mechanism of maintenance of polymorphism at the MHC loci. The results obtained are as follows. (1) The coalescence time for neutral alleles is too short to explain the trans-specific polymorphism at the MHC loci. (2) Under overdominant selection, the coalescence time can be tens of millions of years, depending on the parameter values used. The average heterozygosity and the number of alleles observed are also high enough to explain MHC polymorphism. (3) The pathogen adaptation model proposed by Snell is incapable of explaining MHC polymorphism, since the coalescence time for this model is too short and the expected heterozygosity and the expected number of alleles are too small. (4) From the mathematical point of view, the minority advantage model of frequency-dependent selection is capable of explaining a high degree of polymorphism and trans-specific polymorphism. (5) The molecular mimicry hypothesis also gives a sufficiently long coalescence time when the mutation rate is low in the host but very high in the parasite. However, the expected heterozygosity and the expected number of alleles tend to be too small. (6) Consideration of the molecular mechanism of the function of MHC molecules and other biological observations suggest that the most important factor for the maintenance of MHC polymorphism is overdominant selection. However, some experiments are necessary to distinguish between the overdominance and frequency-dependent selection hypotheses.

Download full-text


Available from: Naoyuki Takahata, Oct 04, 2015
30 Reads
  • Source
    • "The parts of the molecule coding for the peptide binding regions (PBRs) are under strong diversifying or balancing selection, and MHC-genes are the most variable functional genes described in vertebrates to date (Piertney and Oliver 2006). Exactly how the selective pressure is acting on MHC alleles with different PBRs is disputed (van Oosterhout 2009): heterozygote advantage (Doherty and Zinkernagel 1975), rare-allele-advantage (Takahata and Nei 1990), host-pathogen coevolution (Borghans et al. 2004) and MHC-based mating preferences (Penn and Potts 1999; Wedekind et al. 1995) have all been proposed as "
    [Show abstract] [Hide abstract]
    ABSTRACT: We studied variation at the class II gene of the major histocompatibility complex (MHC) in Natterjack toad populations (Bufo [Epidalea] calamita) on islands off the west coast of Sweden. These isolated populations have previously been shown to exhibit low levels of neutral genetic variation. On seven investigated islands we found only two different MHC alleles, indicating that the genetic variation at this locus is also low. The two alleles were found in all populations, although in one population there was only a single heterozygous individual. The Swedish toads showed similar low levels of MHC variation as revealed by previously published data from populations in northern Europe. We did not find a correlation between MHC and neutral genetic variation (as determined by AFLP). However, our findings show that reduced genetic variation in the Swedish Natterjack toads is not restricted to neutral markers, but is likewise reflected at the MHC.
    Conservation Genetics 08/2015; 16(4):1-4. DOI:10.1007/s10592-015-0715-3 · 2.19 Impact Factor
  • Source
    • "Positive selection at the MHC is evidenced by increased nucleotide diversity at the PBR codons, which results in a relatively high rate of nonsynonymous amino acid changes within the mature protein (Hughes and Nei 1988). At the population level, MHC polymorphisms may also result from balancing selection, fueled by the evolutionary ''arms-race'' between the vertebrate immune system and pathogens (Edwards and Hedrick 1998; Takahata and Nei 1990). Balancing selection at the MHC is believed to occur specifically by the processes of overdominance (heterozygote-advantage ; Penn et al. 2002) and frequency-dependent selection (Borghans et al. 2004), which may influence the spectrum of allele diversity through mechanisms such as condition-dependent mate choice and spatiotemporal pathogen dynamics. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The major histocompatibilty complex (MHC) has become increasingly important in the study of the immunocapabilities of non-model vertebrates due to its direct involvement in the immune response. The characterization of MHC class I loci in the lark sparrow (Chondestes grammacus) revealed multiple MHC class I loci with elevated genetic diversity at exon 3, evidence of differential selection between the peptide binding region (PBR) and non-PBR, and the presence of multiple pseudogenes with limited divergence. The minimum number of functional MHC class I loci was estimated at four. Sequence analysis revealed d N /d S ratios significantly less than one at non-PBR sites, indicative of negative selection, whereas PBR sites associated with antigen recognition showed ratios greater than 1 but non-significant. GenBank surveys and phylogenetic analyses of previously reported avian MHC class I sequences revealed variable signatures of evolutionary processes acting upon this gene family, including gene duplication and potential concerted evolution. An increase in the number of class I loci across species coincided with an increase in pseudogene prevalence, revealing the importance of gene duplication in the expansion of multigene families and the creation of pseudogenes.
    Genetica 06/2015; 143(4). DOI:10.1007/s10709-015-9850-5 · 1.40 Impact Factor
  • Source
    • "При этом отбор, действующий на хозяина, принимает характер направленного, дающего преимущество аллелям, с одной стороны обеспечивающим устойчивость к изменившемуся паразиту, а с другой – исходно обладавшим низкой частотой встречаемости. Данный процесс обладает цикличностью и ведет к поддержанию разнообразия и у хозяина, и у его паразита (Takahata, Nei, 1990). Механизмы полового отбора и эффективности размножения могут действовать двумя различными путями: ГКГ-зависимый выбор полового партнера и селективные прерывания беременностей в случае сходства ГКГ-профилей матери и зародыша. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Major histocompatibility complex (MHC) appears to be a suitable tool for solving various tasks of popu- lationgenetics. Information on genetic basis of immunity facilitates understanding of evolutionary his- tory and assessment of current state and prospects of studied population/species survival. On the one hand, MHC variability is maintained through pathogen dependent mechanisms, i.e., directional selection of individuals resistant to diseases, that are present in the environment and balancing selection which gives advantage to those individuals carrying unusual or rare alleles of MHC genes. On the other hand, MHC genes have an influence on reproduction efficiency of individuals. Because of MHC polygeny, its studying requires an application of methods that introduce additional stages between amplification of a certain gene segment and its sequencing. In the article, different tech- niques of allele separation are considered, as well as a simplified version of MHC variability analysis based on the examination of microsatellite loci. Despite the high information value of MHC, it is still not used in zoological studies as often as it deserves. Using as an example predatory mammals of Felidae family which contains quite a few threatened species, we show that a majority of studies on MHC in wild cats is descriptive ones and only few of them deal with genes comparative analysis. The rise of interest to the studies of major histocompatibility complex in non-model species may help not only in solving the fundamental problems of evolution and phylogenetic structure of the family but also in planning the measures for conservation of rare and endangered species exposed to various anthropogenic stresses.
    Zhurnal obshcheĭ biologii 03/2015; 75(4):302-14. · 0.16 Impact Factor
Show more