Each gene is made up of a long sequence of substances called nucleotides; these nucleotides, taken in series of three at a time, specify each amino acid subunit of a protein (see nucleic acid). In a frameshift mutation, a nucleotide is added or deleted to the sequence and the decoding of the entire gene sequence will be radically altered and the amino acid sequence of the protein produced will also be very different. Often the resulting protein is totally ineffective. If one nucleotide substitutes for another in the sequence only one amino acid of the protein will be different, but the effect can be quite dramatic. For example, the inherited sickle cell disease is the result of a mutation that results in the substitution of the amino acid valine for glutamic acid in hemoglobin.

Because proteins called enzymes control most cell activities, a mutation affecting an enzyme can result in alteration of other cell components. A single gene mutation may have many effects if the enzyme it controls is involved in several metabolic processes. Occasionally a mutation can be offset by either another mutation on the same gene or on another gene that suppresses the effect of the first. Certain genes are responsible for producing enzymes that can repair some mutations. While this process is not fully understood, it is believed that if these genes themselves mutate, the result can be a higher mutation rate of all genes in an organism.

Mutations may be induced by exposure to ultraviolet rays and alpha, beta, gamma, and X radiation, by extreme changes in temperature, and by certain mutagenic chemicals such as nitrous acid, nitrogen mustard, and chemical substitutes for portions of the nucleotide subunits of genes. H. J. Muller, an American geneticist, pioneered in inducing mutations by X-ray radiation (using the fruit fly, Drosophila) and developed a method of detecting mutations that are lethal.

In 1901 the observation of mutants, or sports, among evening primrose plants led the Dutch botanist Hugo de Vries to present his theory that new characteristics may appear suddenly and that these characteristics are inheritable; before this time the sources of evolutionary variation were not known and some still believed that evolution resulted from a gradual selection of favorable acquired characteristics. The work of de Vries and of subsequent investigators who demonstrated the distinction between mutation and environmental variations has shown the importance of mutation in the mechanism of evolution.