Allelic exclusion

Allelic exclusion

Humans and many other organisms are "diploid", i.e. they have two copies of each chromosome (one inherited from each parent) in all their somatic cells. Both chromosomes within the pair contain essentially the same genes, but these genes may contain a small number of nucleotide differences. The two copies of a gene on a pair of chromosomes are called alleles. Usually both alleles show similar levels of gene expression.

Allelic exclusion is a process by which the protein from only one allele is expressed while other allele(s) are silenced. It has been observed most often in genes for cell surface receptors and has been extensively studied in immune cells such as B lymphocytes.cite journal | author = Chess A | title = Expansion of the allelic exclusion principle? | journal = Science | volume = 279 | issue = 5359 | pages = 2067–8 | year = 1998 | pmid = 9537917 | doi = ] In B lymphocytes, successful heavy chain gene rearrangement on one chromosome results in the shutting down of rearrangement on the second chromosome. If no successful rearrangement occurs, rearrangement takes place on the second chromosome. If no successful rearrangement occurs on either chromosome, the cell dies. As a result of allelic exclusion, all the antigen receptors on an individual lymphocyte will have the same amino acid sequence in the variable domain of the heavy chain protein. As the specificity of the antigen receptor is modulated by the variable domain of the light chain encoded by one of the immunoglobulin light chain loci, the specificities of B cells containing the same heavy chain recombination event can differ according to their light chain recombination event.

The mechanism by which allelic exclusion occurs is not fully understood.cite journal | author = Mostoslavsky R, Alt FW, Rajewsky K | title = The lingering enigma of the allelic exclusion mechanism | journal = Cell | volume = 118 | issue = 5 | pages = 539–44 | year = 2004 | pmid = 15339659 | doi = 10.1016/j.cell.2004.08.023]

At least two distinct selection events can lead to allelic exclusion. On one hand, one allele of the gene can be transcriptionally silent, which would result in the expression of only the second allele. On the other hand, both alleles can be transcribed, in which case posttrancriptional and posttranslational mechanisms will lead to the elimination of the protein product of one allele.


Further reading

* Cellular and Molecular Immunology (5th Ed.) Abbas AK, and Lichtman AH., Editor: Saunders, Philadelphia, 2003.

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