Transcriptional bias: a non-Lamarckian mechanism for substrate-induced mutations

In bacterial cultures in the stationary phase, substrates can selectively stimulate mutations that lead to their own utilization, but because of apparent conflict with the neo-Darwinian view of evolution the phenomenon has encountered widespread resistance. Building on further evidence for this process, Cairns et al. [Cairns, J., Overbaugh, J. & Miller, S. (1988) Nature (London) 335, 142-145] have suggested a Lamarckian mechanism of directed mutation. This paper proposes an alternative mechanism: transcription induced by the substrate introduces a bias in the random process of mutation, because the resulting single-stranded regions of DNA are more mutable. This stimulation of adaptive mutations by the environment has implications for evolution similar to those of directed mutation, but without contradicting the central "dogma" of molecular genetics. In addition, in eukaryotic cells a mutagenic effect of induction on protooncogenes could contribute to the stimulatory effect of proliferation on carcinogenesis.