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 hypothesis was first proposed in 1988 [1] 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.[2][3]
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".