We noticed that during short-term experimental evolution and carcinogenesis, mutations causing gene inactivation (i.e., nonsense mutations or frameshifts) are frequent. Our meta-analysis of 65 experiments using modified dN/dS statistics indicated that nonsense mutations are adaptive in different experimental conditions and we empirically confirmed this prediction. Using yeast S. cerevisiae as a model we show that fixed or highly frequent gene loss-of-function mutations are almost exclusively adaptive in the majority of experiments.