neutral versus nearly neutral theories

Hughes AL 2008 Near neutrality: leading edge of the neutral theory of molecular evolution. Ann NY Acad Sci 1133:162-179.

• slightly deleterious mutations in coding regions will usually be nonsynonymous
• the ratio of nonsynonymous to synonymous fixed differences between species should often exceed the ratio of nonsynonymous to synonymous polymorphisms within species
• many (probably most) claimed cases of positive selection will turn out to involve the fixation of slightly deleterious mutations by genetic drift

• near neutrality describes conditions under which the neutral theory makes bold predictions
• thus represents the leading edge of the neutral theory, where that theory as a whole stands or falls

• the truly new idea in evolutionary biology is that of Kimura (building on the work of Sewall Wright), which along with Heisenberg's uncertainty principle and Gödel's proof of the incompleteness of mathematics formed part of a 20th century revolution in thought that for the first time revealed the universe as nonalgorithmic
• the originality of Lynch's vision is that he illustrates how nonadaptive forces may have given rise to raw materials that could later be exploited by natural selection
• slightly deleterious mutations can contribute to later adaptive evolution by creating the conditions that make possible a future adaptation