During early development of metazoans, there is an abrupt increase in the need for specific molecules such as ribosomal RNA and messenger RNA molecules for proteins that make up specific cell or tissue types. One way to increase the rate at which such molecules can be formed is to increase the number of genes available for transcription of these specific molecules. Among the repetitive DNA sequences within the genome are hundreds of copies of ribosomal RNA-encoding genes. These genes preexist repetitively in the DNA of the gametes and thus are transmitted in high copy numbers from generation to generation. In some specific organisms such as the fruit fly (Drosophila), there occurs during oogenesis an amplification of a few preexisting genes such as those for the chorion (eggshell) proteins. Subsequently, these amplified genes, presumably generated by a process of repeated initiations during DNA synthesis, provide multiple sites for gene transcription. The dark side of specific gene amplification is the fact that in human cancer cells drug resistance can develop upon extended therapeutic treatment due to the amplification and increased expression of genes that encode proteins that either degrade, or pump drugs from target cells As noted in Chapter 36, the coding sequences responsible for the generation of specific protein molecules are frequently not contiguous in the mammalian genome. In the case of antibody encoding genes, this is particularly true. As described in detail in Chapter 52, immunoglobulins are composed of two polypeptides, the so-called heavy (about 50 kDa) and light (about 25 kDa) chains. The mRNAs encoding these two protein subunits are encoded by gene sequences that are subjected to extensive DNA sequence–coding changes. These DNA coding changes are integral to generating the requisite recognition diversity central to appropriate immune function.

IgG heavy- and light-chain mRNAs are encoded by several different segments that are tandemly repeated in the germline. Thus, for example, the IgG light chain consists of variable (V_L), joining (J_L), and constant (CL ) domains or segments. For particular subsets of IgG light chains, there are roughly 300 tandemly repeated V_L gene coding segments, 5 tandemly arranged JL coding sequences, and roughly 10 C_L gene coding segments. All of these multiple, distinct coding sequences are located in the same region of the same chromosome, and each type of coding segment (V_L, J_L, and C_L) is tandemly repeated in head-to-tail fashion within the segment repeat region. By having multiple V_L, J_L, and C_L segments to choose from, an immune cell has a greater repertoire of sequences to work with to develop both immunologic flexibility and specificity. However, a given functional IgG light chain transcription unit—like all other “normal” mammalian transcription units—contains only the coding sequences for a single protein. Thus, before a particular IgG light chain can be expressed, single V_L, J_L, and C_L coding sequences must be recombined to generate a single, contiguous transcription unit excluding the multiple nonutilized segments (ie, the other approximately 300 unused V_L segments, the other 4 unused J_L segments, and the other 9 unused CL segments). This deletion of unused genetic information is accomplished by selective DNA recombination that removes the unwanted coding DNA while retaining the required coding sequences: one V_L , one J_L , and one C_L sequence. (V_L sequences are subjected to additional point mutagenesis to generate even more variability—hence the name.) The newly recombined sequences thus form a single transcription unit that is competent for RNA polymerase II mediated transcription into a single monocistronic IgG light chain-encoding mRNA. These multiple IgG-gene recombination and mutation events are generated in a single clonal population of B-cells. Although the IgG genes represent one of the best-studied instances of directed DNA rearrangement modulating gene expression, other cases of gene regulatory DNA rearrangement have been described.

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قسم شؤون المعارف الإسلامية يحتفي بإرث الأديب الراحل علي أنكيل ويتسلم مكتبته الشخصية

سماحة السيد الصافي يدعو إلى توثيق الأفكار والأحداث لحماية الإرث العراقي من الاندثار بغية نقله سليمًا للأجيال القادمة

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مواضيع ذات صلة

Regulation of Messenger RNA Stability Provides Another Control Mechanism

The DNA Binding & Transactivation Domains of Most Regulatory Proteins are Separate DNA

Several Structural Motifs Compose the DNA-Binding Domains of Regulatory Transcription Factor Proteins

Reporter Genes Are Used to Define Enhancers & Other Regulatory Elements That Modulate Gene Expression

Certain DNA Elements Enhance or Repress Transcription of Eukaryotic Genes

Epigenetic Mechanisms Contribute Importantly to the Control of Gene Transcription

The Chromatin Template Contributes Importantly to Eukaryotic Gene Transcription Control

The Genetic Switch of Bacteriophage Lambda (λ) Provides Another Paradigm for Understanding the Role of Conditional Regulatory Protein-DNA Interactions in Transcriptional Control in Eukaryotic Cells

Analysis of Lactose Metabolism in E. coli Led to the Discovery of the Basic Principles of Gene Transcription

Biologic Systems Exhibit Three Types of Temporal Responses to a Regulatory Signal

Regulated Expression of Genes is Required for Development, Differentiation, & Adaptation

Posttranslational Processing Affects the Activity of many Proteins