There are many mechanisms which lead to polymorphisms. The mechanisms differ from MHC to antibody/TCR genes.
1. MHC MECHANISMS
• Mate choice based on MHC: When mating occurs between different phenotypic traits they display negative mating. Studies of inbred groups are helpful for human mate choice studies. Low levels of HLA polymorphism reduce chances of random matches in distinct HLA.
• Effects of HLA on the outcome of pregnancy: The increased sharing of HLA alleles in couples that have experienced recurrent spontaneous abortions, relative to control couples, has been observed in several studies. This has great effect on the foetal loss. Interactions between mother and baby may play an important role in HLA polymorphism.
Pathogen co evolution Mechanism
• The mechanisms such as heterozygous advantage, frequency dependent selection and fluctuating selection are pathogen driven selections when specific alleles are favoured because of their ability to provide protection from pathogen.
• Heterozygous advantage: This is based on the fact that two suites of pathogens are recognised. One for each allele and hence have a higher fitness then homozygotes. Overdominance selection increases selection of heterozygotes. Overdominance maintains polymorphism for two reasons:
• Segregation load: Here there is heterozygous advantage, random mating here produces homozygote individuals with lower fitness. This may lead to extinction of many individuals.
Theoretical Assessment of combination of selection coefficients: These are important for separating the. Overdominance is one of the main causes for extensive distribution of alleles at HLA loci.
• Frequency dependent selection: The values are not fixed they change in proportion to allele frequencies. Minority advantage is in relevance to MHC and it is a form of frequency dependent selection. Peptide binding changes when the pathogen mutates and these are selectively favoured. There will be reduction in fitness of frequent HLA molecule. Selective advantage is seen under frequency dependent selection as pathogens are not adapted to them.
• Fluctuating Selection: If the frequency of pathogen changes constantly; different histocompatibility molecules are selected at different times. Fluctuating selections willingly sustain genetic variance in species where generations overlap in a way that only a portion of the population is exposed to selection.
2. ANTIBODY GENE MECHANISMS
In BCR there is balance selection and directional selection are the mechanisms associated with BCR. The directional selection is found an all except in one particular species of rabbits due to overdominance selection. In directional selection there is favourable selection of a desired allele and there will be increase of this particular allele. Directional selection is contrasting to balancing selection where selection there is selection favours multiple alleles. Directional selection favours heterozygous selection. A balancing polymorphism is a situation in which balancing selection in a given population can maintain stable frequencies. If there is an increased genetic variation between alleles it shows the presence of balancing selection. Fitness and disease association of haplotypes is also an important mechanism to determine polymorphism. Only one report so far of a rabbit and snowshoe hare has been reported as a polymorphism in association with BCR germline.
3. TCR GENE MECHANISMS
TCR and antibody selection procedure is not stringent due to multiple copies of gene sequences. The TCR has no specific mechanism but it is conserved through speciation like BCR.
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