Fundamentals of Molecular Biology - V.I. Rezyapkin 2009

Genome Rearrangements
Amplification

The process of generating additional copies of DNA sequences is known as Gene amplification. The resulting copies of DNA sequences (genes) may either integrate into The Genome or become part of extrachromosomal DNA. An increased copy number ensures the synthesis of large amounts of the product encoded by that specific gene. Amplification can be either programmed or unprogrammed. In programmed amplification, the copy number increases in specific Cells at a defined time point, just before The Cell requires large quantities of the gene product. Unprogrammed amplification, on the other hand, occurs in response to an external factor, and the resulting product of the amplified gene helps mitigate the NEGATIVE IMPACT OF that factor.

Programmed amplification

A classic example of programmed amplification is the amplification of eggshell protein genes in the follicular cells of Drosophila. In insects, the follicular cells surrounding the maturing oocyte must rapidly synthesize and secrete large quantities of Proteins that form the eggshell. While some insects achieve this through the efficient METABOLISM/31.html">Transcription of repetitive genes encoding these proteins, in Drosophila these genes are present as single copies. However, a few hours before Protein Synthesis begins, these genes undergo amplification followed by high-level expression, thereby ensuring the rapid production of substantial amounts of protein. These amplified genes reside within the Drosophila Chromosomes.

rRNA genes can also undergo programmed amplification. It is well known that most genomes contain numerous copies of rRNA genes, reflecting the cell's high demand for these products. Nevertheless, these genes can be further amplified in oocytes—for instance, in Xenopus oocytes, where rRNA genes are amplified a thousand-fold. These amplified genes are organized into large extrachromosomal circular DNA molecules containing up to a hundred repeating units of rRNA genes. In many cases, unprogrammed amplification helps compensate for insufficient enzyme activity within cells, such as when cells are exposed to Enzyme Inhibitors. When cells are cultured in the presence of a specific enzyme inhibitor, the majority die due to an insufficient supply of the product normally catalyzed by that enzyme. However, a small fraction of cells survive and multiply under these conditions. If these surviving cells are subsequently cultured at higher concentrations of the inhibitor, the same scenario repeats: only a minor subset of cells survives and grows. By gradually increasing the inhibitor concentration, it is possible to isolate cells resistant to high levels of the inhibitor. To counteract the inhibitory effect, these cells produce large amounts of the enzyme. This increased enzyme synthesis is achieved through the amplification of its gene, leading to elevated mRNA production, whose subsequent Translation results in the enhanced intracellular level of the enzyme.