Insertional mutagenesis

Insertional mutagenesis is mutagenesis of DNA by the insertion of one or more bases.

Insertional mutations can occur naturally, mediated by virus or transposon, or can be artificially created for research purposes in the lab.

This is a technique used to study the function of genes. A transposon, such as the Drosophila melanogaster P element, is allowed to integrate at random locations in the genome of the organism being studied. Mutants generated by this method are then screened for any unusual phenotypes. If such a phenotype is found then it can be assumed that the insertion has caused the gene relating to the usual phenotype to be inactivated. Because the sequence of the transposon is known, the gene can be identified, either by sequencing the whole genome and searching for the sequence, or using the polymerase chain reaction to amplify specifically that gene.

As mentioned in the introduction, insertional mutagenesis refers to mutation of an organism caused by the insertion of additional DNA bases into the organism's preexisting DNA. Because many viruses (not all of them) integrate their own genome into the genome of their host cells in order to replicate, mutagenesis caused by viral infections is a fairly common occurrence. Not all integrating viruses cause insertional mutagenesis, however.

It is important to note that not all DNA insertions will lead to a noticeable mutation. In recent gene therapy trials, the lentiviral vectors used showed no tendency to disrupt gene function or promote oncogenic development. Because of these advances, gene therapy with integrating vectors is now considered safe and is the preferred method of gene transfer due to the permanent nature of the integration compared to the transient persistence of non-integrating viruses. For those viruses such as gamma-retroviruses that do tend to integrate their DNA in genetically unfavorable locations, the severity of any ensuing mutation depends entirely on the location within the host's genome wherein the viral DNA is inserted. If the DNA is inserted into the middle of an essential gene the effects on the cell will be drastic. Additionally, insertion into the promoter region of a gene can cause equally drastic effects. For instance, if the viral DNA is inserted into a repressor, the gene corresponding to that promoter may be over expressed – leading to an overabundance of its product and altered cellular activity. If the DNA is inserted into an enhancer region, the gene may be under-expressed – leading to relative absence of its product, which can significantly interrupt the activity of the cell.

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