Spontaneous mutations are thought to occur primarily in growing cells. However, spontaneous mutations also arise in nutritionally deprived cells, and in some cases this process appears to be adaptive. Here it is reported that when a Lac(-) strain of Escherichia coli is under selection for lactose use, the spectrum of Lac(+) mutations that arises is different, and simpler, than that arising without selection. Mutations appearing during selection were mainly one-base deletions in runs of iterated bases. Similar mutations occurring in repetitive DNA elements are associated with a variety of human hereditary diseases and are increased in cells that cannot correct heteroduplex DNA.