Can gene-inactivating mutations lead to evolutionary novelty?

Evolutionary novelty is difficult to define. It typically involves shifts in organismal or biochemical phenotypes that can be seen as qualitative as well as quantitative changes. In laboratory-based experimental evolution of novel phenotypes and the human domestication of crops, the majority of the mutations that lead to adaptation are loss-of-function mutations that impair or eliminate the function of genes rather than gain-of-function mutations that increase or qualitatively alter the function of proteins. Here, I speculate that easier access to loss-of-function mutations has led them to play a major role in the adaptive radiations that occur when populations have access to many unoccupied ecological niches. I discuss five possible objections to this claim: that genes can only survive if they confer benefits to the organisms that bear them, antagonistic pleiotropy, the importance of pre-existing genetic variation in populations, the danger that adaptation by breaking genes will, over long times, cause organisms to run out of genes, and the recessive nature of most loss-of-function mutations. Andrew Murray proposes that mutations that impair gene function play a major role in the evolution of novel traits.