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Mutagenesis

dna called sequence genetic

Mutagenesis is the induction of genetic change in a cell by the alterations in the cell's genetic material (usually deoxyribonucleic acid [DNA]). This change or alteration can subsequently be inherited from one cell to the next. While many mutations are benign, some can be detrimental and cause human genetic disease. If the mutation occurs in a gamete (sex cell), the genetic alteration may be passed to subsequent generations. Mutations provide a mechanism for evolution if the mutations in the DNA produce a new or modified protein that has enhanced or new beneficial functions such that this newly acquired characteristic has a selective survival advantage and thus will be more likely to be passed down from one generation to the next. Mutations in somatic cells, or cells that have undergone differentiation and will not have the potential to develop into any other cell types are usually spontaneous and not inherited.

Mutagenesis can result in alteration of an individual gene, or a specific letter in the DNA alphabet called a nucleotide. There are four nucleotides, adenine, guanine, cytosine, and thymine. Mutagenesis—or the process acquiring mutations—can be in the form of a point mutation, a deletion, or a duplication in the DNA sequence. A single nucleotide change, called a point mutation, can cause a genetic disease if it occurs in a gene important for normal cellular function. Deletions involve deleted sequence of DNA that can be in a coding gene sequence (called an exon) or a noncoding sequence of the gene (called an intron) or the noncoding sequence that separates genes. Deletions can be in a single nucleotide or span several genes. A duplication involves a sequence of DNA that gets repeated.

Mutagenesis can occur as the result of exposure to ionizing radiation and certain chemicals. Ionizing radiations include cosmic rays, x rays, and ultraviolet light. It is of interest to note that melanoma, caused almost exclusively by exposure to the ultraviolet radiation from the sun, is the most rapidly increasing lethal cancer in the United States. In melanoma, ultra violet radiation induces what is called thymine dimers. This means that two thymine nucleotides next to each other in a DNA sequence form an abnormal bond. Thymine dimers in a skin cell can lead to skin cancer. The heightened prevalence of melanoma is presumably due to increased ultraviolet radiation exposure of skin most likely from depletions in the ozone layer.

Mutations that affect tumor suppressor genes can result in uncontrollable cellular growth, also called cancer. If this cancer is not detected early and removed, it can become vascularized and leak into the bloodstream. If it metastizes in this way, the cancer can quickly spread to other organs. Additionally, a number of chemicals have been identified as mutagenic such as the common household cleaner bleach. Many chemicals intercalate into the DNA double helix and cause errors during DNA replication. Chemicals that bind to DNA are called DNA adducts. There are many environmental carcinogens or cancer-causing chemicals that induce mutagenesis.

Teratogenesis is the development of congenital abnormalities due to the exposure to substances during development called teratogens. Many teratogens are mutagens in that they can cause mutations in DNA. An example of a teratogen is thalidomide. Thalidomide was used in the 1950s to as a treatment for morning sickness in pregnant women. It was later found to cause birth defects. In this case, it disrupted developmental processes resulting in abnormalities affecting normal development.

Despite the many different ways that mutagenesis can occur, mechanisms for DNA repair exist that help maintain the integrity of the genome. One mechanism, called nucleotide excision repair, involves recognition and removal of damaged DNA by nicking it where there is a point mutation, removing the damaged nucleotide sequence, re-synthesis to add the correct nucleotide, and DNA ligation of the nicked DNA to seal the DNA where it is being repaired.

Resources

Books

Robert L. Nussbaum, Roderick R. McInnes, Huntington F. Willard. Genetics in Medicine. Philadelphia: Saunders, 2001.

David L. Rimoin. Emery and Rimoin's Principles and Practice of Medical Genetics. London; New York: Churchill Livingstone, 2002.


Bryan Cobb

KEY TERMS

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Deoxyribonucleic acid (DNA)

—The genetic material in a cell.

Genotype

—The full set of paired genetic elements carried by each individual, representing the its genetic blueprint.

Mutation

—Molecular defect in DNA.

Nucleotide

—Molecular unit that is the building block of DNA.

Phenotype

—The outward manifestation of the genotype, including an organism's morphological, physiological, and many behavioral attributes.

[back] Mutagen - History, Where Mutagens Exist, How Mutagens Work, Somatic Vs. Germline Mutations, Types Of Mutagens

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