Revising the neutral theory

So we've now produced empirical evidence that many mutations are not neutral. Does this mean that we throw the neutral theory of molecular evolution away? Hardly. We need only modify it a little to accomodate these new observations.

• Most non-synonymous substitutions are deleterious. We can actually generalize this assertion a bit and say that most mutations that affect function are deleterious. After all, organisms have been evolving for about 3.5 billion years. Wouldn't you expect their cellular machinery to work pretty well by now?

• Most molecular variability found in natural populations is selectively neutral. If most function-altering mutations are deleterious, it follows that we are unlikely to find much variation in populations for such mutations. Selection will quickly eliminate them.

• Natural selection is primarily purifying. Although natural selection for variants that improve function is ultimately the source of adaptation, even at the molecular level, most of the time selection is simply eliminating variants that are less fit than the norm, not promoting the fixation of new variants that increase fitness.

• Alleles enhancing fitness are rapidly incorporated. They do not remain polymorphic for long, so we aren't likely to find them.

As we'll see, even these revisions aren't entirely sufficient, but what we do from here on out is more to provide refinements and clarifications than to undertake wholesale revisions.