Random with Respect to Fitness or External Selection? An Important but Often Overlooked Distinction.

Mutations are often described as being "random with respect to fitness." Here we show that the experiments used to establish randomness with respect to fitness are only capable of showing that mutations are random with respect to current external selection. Current debates about whether or not mutations are directed may be at least partially resolved by making use of this distinction. Additionally, this distinction has important mathematical, experimental, and inferential implications.