Molecular Evolution Activities

The Nearly Neutral Theory of Molecular Evolution

The Nearly Neutral Theory of Molecular Evolution

Over the last few decades, the term “nearly neutral mutations” has been used in various ways. However, it was Tomoko Ohta who first developed an independent theory on the fate of nearly neutral mutations, and named it the "nearly neutral theory" in 1973. At that time, Ohta primarily focused on mutations that are "slightly deleterious” instead of both “slightly deleterious” and “slightly advantageous” mutations because of the wide belief of the "status quo" argument among molecular evolutionists. The "status quo" meant that gene function was already close to its optimum in general, and advantageous mutations were extremely rare. Ohta incorporated this “status quo” argument to her nearly neutral theory in the early 1970s; therefore, Ohta did not see any need to discuss slightly advantageous mutations back then.
Toward the end of the 1980s, however, increasing amounts of data showed the existence of slightly advantageous mutations and the effects of positive selection on them. Therefore, Ohta modified her original nearly neutral theory by incorporating the fate of slightly advantageous mutations, and proposed this modified theory as “nearly neutral theory of molecular evolution” in a series of two papers published in 1990 and1991.

There are several other differences between the earlier model of the nearly neutral theory and the later one. To differentiate, Ohta also calls the earlier model, the “shift model”(1973) and the later one the “fixed model” (1990, 1991). Please see more details on these models in the Discussion Transcript from the 2002 Dibner Workshop.

There is also much confusion for the differences between Kimura’s neutral theory and Ohta’s nearly neutral theory. The main difference between Ohta’s nearly neutral theory and Kimura’s neutral theory is while Kimura put his focus on so-called “strictly neutral mutations” (this phrase is specified by Ohta), Ohta was more interested in the evolutionary mechanisms of the “border line mutations” or the “nearly neutral mutations,” (i.e. mutations which are not strictly neutral nor are strongly selected).

The most notable yet overlooked difference between these two theories is the effect of population sizes. Simply, population size does not effect on neutral mutations. For nearly neutral mutations in small populations, the effects of selection are also extremely limited and the fate of them is also determined by random genetic drift just like neutral mutations. However, the effects of selection are not ignorable in a large population for nearly neutral mutations.
The nearly neutral theory in general requires many more parameters because of the characteristics of these mutations. For this reason, the most frequent criticism of the nearly neutral theory is that it is too complex. Neutralists, including Kimura, argue that a theory needs to be simple, easy to be understood, accepted, and applied. Yet, Ohta argues that her theory explains the “actual natural populations” better.

The current focus of Ohta’s research is seeking a possibility to apply the nearly neutral theory to the morphological level evolution.

For more on the nearly neutral theory follow the links to the right.

This page was written by Tomoko Y. Steen. It was last updated 9/9/2004.



  • Topics
    • Discussion Transcript concerning the Nearly Neutral Theory
    • Video Clips of Tomoko Ohta
    • Profile of Tomoko Ohta