For several decades, finding an improved strain of a microorganism depended on simple selection from natural variants or production of mutants. Natural mutation rates are slow ( on the order of one organism in one million is a mutant ), but irradiation or chemical treatment can induce mutation. This is a helter-skelter approach, and the usual dosage that gives useful numbers of mutants results in a culture that looks rather sick. A very high percentage of mutants are inferior to their parent strain, and most mutations are lethal. Of the surviving mutants, there is only a very remote possibility that they can produce the desired product more quickly or in higher concentrations than were observed with the parent. Nevertheless, countless numbers of mutants were developed and tested in order to achieve dramatic improvements in yields of antibiotics and other biochemicals.
The discovery that genes could be cleaved, altered, and recombined changed genetics to a more exact science. It is now routine to move genetic elements from one organism to another and to cross the boundaries between families. Human insulin is produced by E. coli that has portions of human genetic material.
The field of genetic engineering is based on removing, modifying, cutting, or splicing of the nucleic acids that make up genes. These genes code for the formation of enzymes, structural elements of a cell, or for the metabolic machinery. The concept is to add or to delete genetic material so that a cell will produce more of a desired product. This happens because the cell diverts less resources to other cell functions or because an entirely new capability is created.
Genetic manipulations depend on enzymes (such as restriction endonucleases) that cleave nucleic acid strands at very specific locations and on other enzymes called ligases that will reattach genetic material. Although sequences of nucleic acids can be synthesized by an organic chemist, most sequences to be added come from living cells. It is common to take a sequence from one type of cell and to insert it into the gene of an entirely different cell. Various methods such as using a phage (virus for a microorganism) are used to get new genetic material inside a cell.
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