Abstract: Despite the fact that all-important protein motifs encoded in gene sequences are generally considered to have been generated solely through a gradual and undirected process of change, the idea lacks empirical evidence and also suffers from theoretical difficulties. More recently, sudden developments such as through the exonization of non-coding DNA, as well as frameshift mutation, have been suggested as another source of evolutionary innovation. A mathematical model was used here to describe the combined action of both cumulative natural selection and random drift, relative to that of an alternative mechanism of artificial selection, in the origination of a hypothetical multi-residue sequence motif. A computer simulation of the model quantifiably demonstrates the marked inefficacy of standard forces in developing these molecular features when compared to the power of a directed or self-organizing process. An examination of how natural population shifts, including migration and isolation, as well as intragenic recombination, may serve to facilitate this particular case is also explored. An evolutionary accretion for novel motifs is concluded as being eminently feasible, although not one wholly reliant on the outcome of chance and differential reproduction.Abstract: Despite the fact that all-important protein motifs encoded in gene sequences are generally considered to have been generated solely through a gradual and undirected process of change, the idea lacks empirical evidence and also suffers from theoretical difficulties. More recently, sudden developments such as through the exonization of non-coding DNA...Show More