Neutral and nonneutral mutations: the creative mix--evolution of complexity in gene interaction systems.

Random drift, while indifferent to the functionality of the molecular features on which it acts, may nevertheless affect evolving molecular mechanisms. It can lead to functional novelty in either gene structure or regulation. In particular, a nearly neutral (in the sense of Ohta), somewhat deleterious mutation can result in a loss of efficiency in gene regulation, and this loss is expected at times to be compensated by a selected event of a particular type: the use of an additional regulatory factor. An accumulation of additional regulatory factors, implying a combination of events of drift and selection, can permit regulatory systems to achieve an increase in both specificity and complexity as mere byproducts of a particular repair process. Nearly neutral mutations thus may, at times, constitute a required pathway for increases in gene interaction complexity. The process seems to point to an inbuilt drive-built into the gene interaction system itself-toward the evolution of higher organisms. This is a matter worthy of experimental exploration, since the general foundations for the evolution of "higher" from "lower" organisms seems so far to have largely eluded analysis.