Mutation

For much of our recorded history, the sudden appearance of an altered person, plant, animal, or other living creature was mysterious and feared, and was typically attributed to some divine intervention. Beginning with the observations of Gregor Mendel on the effects of breeding peas of differing appearance, the genetic basis of mutation became recognized and accepted. A greater understanding of the mechanics of mutation came from the experiments conducted by Thomas H. Morgan in 1910 with fruit fly mutations, and George W. Beadle and Edward L. Tatum in the 1940s on bread mold mutations. The publication of the structure and composition of DNA by Francis Crick and James Watson in 1953 paved the way for the understanding of the molecular basis of mutation.

In eukaryotic organisms such as humans every cell contains DNA arranged on threadlike structures. The structures are called chromosomes. Within the chromosomes lie the regions of DNA called genes that contain the information for proteins. Human beings carry about 30,000 genes on their chromosomes. If the DNA of a particular gene is altered, that gene will become changed. If the change is minor, the mutation may not even be apparent or may be irrelevant to the three dimensional structure and the function of the protein that is produced. But, even an alteration at a single site in a gene can produce drastic alteration of the protein. The protein may not function correctly or may not function at all.

Just one missing or abnormal protein can have an enormous effect on the entire body. For example, the multiple effects that are associated with an albino are the result of one missing protein.

DNA is made up of subunits known as nucleotide bases. There are four kinds of bases: adenine (A), cytosine (C), guanine (G), and thymine (T). The arrangement and different combinations of the bases determines the genetic information, analogous to the arrangement of letters to form words. Mistakes in the genetic code occur when any of these nucleotide bases are absent or duplicated or misplaced. Mutation can be thought of as a kind of molecular typographical error.

As an example, a stretch of DNA could have the following arrangement of bases: ATCTTTGGT. A mutation could occur that produces repeats of some of the bases, as in the italicized region that follows: ATCATCATCTTTGGT. The added bases disrupt the arrangement of the bases, and so disrupt the information contained in the base sequence. An example is Huntington's disease. The presence of two copies of a mutated gene (one from each parent) causes the progressive degeneration of the nervous system and leads to death of the afflicted person in their 40s or 50s. The Huntington's disease mutation is caused by a repeating sequence of three bases in the gene.

Other mutations include the presence of an incorrect base at a certain point, and a missing base (a deletion mutation).

An example of a disease that results from a deletion mutation is cystic fibrosis. The presence of mutated genes in which three thymine bases are absent produces cells in the lungs that are defective in the transport of molecules such as sodium. A result is the accumulation of mucus in the lungs. Bacteria readily colonize the mucus and become resistant to treatments intended to kill them. As well, the host's immune response to the invading bacteria causes progressive damage to lung tissue. The infections and impaired lung function can cause a premature death.

Mutational errors can extend to include more than just one base of a chromosome. Humans normally have 23 pairs of chromosomes. But mutations can produce a fetus that has an extra copy or copies of a chromosome. The unique physical appearance and retarded mental faculties associated with Down syndrome arise when three copies of chromosome 21 are present. Another type of chromosomal mutation occurs when portions of two adjacent chromosomes swap places with each other. Such a translocation mutation between chromosomes 9 and 22 lead to a certain type of leukemia.

Mutations that occur in the egg or sperm cells of a eukaryote are called germinal mutations. These mutations can be inherited by subsequent generations. In contrast, somatic mutations, which occur in cells other than sex cells, cannot be inherited.