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According to the original Darwinian view of evolution, adaptation happens through sequential fixation of adaptive changes in the population. However, neutral and deleterious mutations can also fix in populations. Once a deleterious mutation arises, its negative effect on the organism’s fitness can be mitigated through compensatory evolution. Thus, compensatory evolution is an adaptive process that suppresses the effect of a harmful mutation. Although previous studies revealed several examples of compensatory evolution, we still have only a limited knowledge about its propensity and evolutionary consequences. To answer these questions, we set out to study the capacity of the brewer’s yeast genome to compensate the complete loss of genes