Occasionally, single-letter misspellings in the genetic code, known as point mutations, occur. Point mutations that alter the resulting protein sequences are called nonsynonymous mutations, while those that do not alter protein sequences are called silent or synonymous mutations. Between one-quarter and one-third of point mutations in protein-coding DNA sequences are synonymous. Those mutations have generally been assumed to be neutral, or nearly so. A new study involving the genetic manipulation of yeast cells shows that most synonymous mutations are strongly harmful.