Directed mutagenesis, also known as directed mutation, is a hypothesis proposing that organisms can respond to environmental stresses through directing mutations to certain genes or areas of the genome.
The Russian ichthyologist Lev Berg proposed directed mass mutations as the main mechanism for evolution in his anti-Darwinian book Nomogenesis; or, Evolution Determined by Law (1922). Early studies of "directed mutation" were performed by German geneticists. Richard Goldschmidt in 1929 due to his experiments on drosophila through exposure to elevated temperatures had claimed to have produced evidence for directed mutation. Viktor Jollos (1887-1941) in the 1930s had also carried out experiments on drosophila and written that his results had confirmed Goldschmidt's work which was evidence for direct mutation in contrast to natural selection. However later American geneticists were unable to replicate these experiments.
The hypothesis of directed mutagenesis was first proposed in 1988  by John Cairns, of Harvard University who was studying Escherichia coli that lacked the ability to metabolize lactose. He grew these bacteria in media in which lactose was the only source of energy. In doing so, he found that the rate at which the bacteria evolved the ability to metabolize lactose was many orders of magnitude higher than would be expected if the mutations were truly random. This inspired him to propose that the mutations that had occurred had been directed at those genes involved in lactose utilization.
Later support for this hypothesis came from Susan Rosenberg, then at the University of Alberta, who found that an enzyme involved in DNA recombinational repair, recBCD, was necessary for the directed mutagenesis observed by Cairns and colleagues in 1989.
The directed mutagenesis hypothesis was challenged in 2002, when John Roth and colleagues showed that the phenomenon was due to general hypermutability due to selected gene amplification, and was thus a standard Darwinian process. Later research published in 2006 by Jeffrey D. Stumpf, Anthony R. Poteete, and Patricia L. Foster, however, concluded that amplification could not account for the adaptive mutation and that "mutants that appear during the first few days of lactose selection are true revertants that arise in a single step".
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