Mutation and Adaptation: The Directed Mutation Controversy in Evolutionary Perspective

A central tenet of evolutionary theory is that mutation is random with respect to its adaptive consequences for individual organisms; that is, the production of variation precedes and does not cause adaptation. Several recent experimental reports have challenged this tenet by suggesting that bacteria (and yeast) "may have mechanisms for choosing which mutations will occur" (6, p. 142). The phenomenon of nonrandom mutation claimed in these experiments was initially called "directed mutation" but has undergone several name changes during its brief and controversial history. The directed mutation hypothesis has not fared well; many examples of apparently directed mutation have been rejected in favor of more conventional explanations, and several reviews questioning the validity of directed mutation have appeared (53, 54, 59-61, 79, 80). Nonetheless, directed mutation has recently been reincarnated under the confusing label "adaptive mutation" (5, 23, 24, 27, 35, 74). Here we discuss the many experimental and conceptual problems with directed/adaptive mutation, and we argue that the most plausible molecular models proposed to explain "adaptive mutation" are entirely consistent with the modem Darwinian concept of adaptation by natural selection on randomly occurring variation. In the concluding section of the paper, we discuss the importance of an informed evolutionary approach in the study of the potential adaptive significance of mutational phenomena. Knowledge of the molecular bases of muta-