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ALL BOLDED TEXT IS WHAT WAS ORIGINALLY IN THE STUB AND IS NOT MY OWN WRITING. MY ASSIGNMENT PORTION IS THE UNBOLDED TEXT WHICH CAN BE LOCATED IN THE INTRODUCTORY SECTION AS WELL AS THE SECTION ON ALLELIC EXCLUSION IN MATING-TYPE SWITCHING IN YEAST.
Allelic Exclusion[edit]
Allelic exclusion is a process by which only one allele of a gene is expressed while the other allele is silenced. For autosomal genes, diploid organisms inherit one copy from each parent. In the case of allelic exclusion, there is a differential treatment of the two alleles such that there is preferential expression of one allele over the other. This results in monoallelic gene expression.[1][2]
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 posttranscriptional and posttranslational mechanisms will lead to the elimination of the protein product of one allele.
Though the mechanism by which allelic exclusion occurs is not fully understood.[1]
Allelic Exclusion in Mating-Type Switching in Yeast[edit]
Some strains of yeast including Saccharomyces cerevisiae are able to switch between two mating types, a or α. This mating-type switching is an example of allelic exclusion which results in the preferential expression of one allele while the other remains transcriptionally silent. Yeast mating-type switching is accomplished through programmed gene rearrangement which involves DNA rearrangements for the purpose of regulation of expression of particular genes.[1] The mating type of the cell is determined by the information present at the MAT locus located on chromosome three. The MAT locus carries one of two possible sets of genetic information; MATa or MATα. If the yeasts genotype at the MAT locus is a, it is considered the a mating type; if it's genotype is α at the MAT locus, it's mating type is α. These two mating types are genetically distinct from one another, each with unique DNA sequences.[1][3]
Strains with the dominant allele encoding the HO endonuclease have the ability to switch its mating-type every generation. If the strain has the recessive allele, ho, its mating-type is considered stable and changes with a frequency of only 1 in 1 000 000.[1][3] The HO endonuclease is responsible for introducing site-specific double-stranded breaks in the DNA at the MAT locus during mating-type switching, providing the opportunity for an alternate allele to be incorporated.[1] [4] Two additional loci important in this process are the HMRa locus and the HMLα locus. Although silenced through epigenetic mechanisms and therefore not expressed, these loci contain the genetic information sequences for the a-mating-type and the α-mating-type respectively. These loci are used in mating-type switching to provide the genetic information in the form of DNA for the new mating-type.[1][3]
Mating-type switching begins when the HO endonuclease introduces double-stranded breaks at the MAT locus. This double-stranded break triggers a repair system that relies on homologous recombination in which there is an exchange of DNA between homologous DNA sites.[5] Homologous sites flank the MAT, HMR, and HML loci, which allows homologous recombination to occur between these loci. The original genotype at the MAT locus is a good indicator of which mating-type the cell will switch to since there is preferential switching to the type opposite the original due to an enhancer/repressor mechanism.[1] [6] The selected HMRa or HMLα locus is copied and inserted into the MAT locus, while the original genes of the MAT locus are displaced and degraded. The new mating-type is then expressed at the MAT locus. The HMRa and HMLα loci are still present on the chromosome and contain the information for each mating-type but are kept in a heterochromatic state to repress transcription. Although the HMRa and HMLα loci are not expressed in this state, they are still available for future recombination events.[1]
In yeast mating-type switching, either the a or α allele is expressed while the other allele remains transcriptionally silent. Through this process the HMRa and HMLα alleles are treated differently in such a way that the allele opposite the original mating-type is preferentially expressed completing the mating-type switch and demonstrating allelic exclusion.[1]
Allelic exclusion in B-Lymphocytes[edit]
Allelic exclusion has been observed most often in genes for cell surface receptors and has been extensively studied in immune cells such as B lymphocytes.[2] In B lymphocytes, successful heavy chain gene rearrangement of the genetic material from one chromosome results in the shutting down of rearrangement of genetic material from the second chromosome. If no successful rearrangement occurs, rearrangement of genetic material on the second chromosome takes place. 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.
Allelic exclusion in sensory neurons[edit]
A study published in 2006 showed that CpA-methylation helps for allelic exclusion in sensory neurons.[3]
- ^ a b c d e f g h i Allison, Lizabeth A. (2012). Fundamental Molecular Biology. John Wiley & Sons, Inc. pp. 383–398. ISBN 9781118059814.
- ^ Nussbaum 1., McInnes 2., Willard 3., Robert L. 1., Roderick R. 2., Huntington F. 3. (2007). Genetic in Medicine. Elsevier Inc. p. 38. ISBN 9781416030805.
{{cite book}}: CS1 maint: multiple names: authors list (link) CS1 maint: numeric names: authors list (link) - ^ a b c Nasmyth, Kim A. (1982). "Molecular Genetics of Yeast Mating Type". Annual Reviews of Genetics. PMID 6760802.
- ^ Kraus 1. Leung 2. Haber 3., Eliyahu 1. Wai-Ying 2. James E. 3. (July 17, 2001). "Break-induced replication: A review and an example in budding yeast". Proceedings of the National Academy of Science. PMID 11459961.
{{cite journal}}: CS1 maint: numeric names: authors list (link) - ^ Alberts 1. Johnson 2. Lewis 3. Raff 4. Roberts 5. Walter 6., Bruce 1. Alexander 2. Julian 3. Martin 4. Keith 5. Peter 6. (2002). Molecular Biology of the Cell. New York: Garland Science. ISBN 0815340729.
{{cite book}}: CS1 maint: numeric names: authors list (link) - ^ Haber, James E. (1998). "Mating-type gene switching in Saccharomyces cerevisiae". Annual Review of Genetics. PMID 9928492.