Synonymous mutations in yeast genes are not always neutral as previously thought. Researchers tested mutations in 21 genes and found that most synonymous mutations actually reduced the fitness of the yeast. These mutations also affected the level of gene expression. Nonsynonymous mutations had more variation in fitness across different environments compared to synonymous mutations. This suggests that fewer nonsynonymous mutations are always harmless in changing environments, which may explain why nonsynonymous mutations are less common than synonymous mutations. This new understanding could change how we think about mutation, selection, population size, evolution, and disease mechanisms.