A possible origin of novel coding sequences is the removal of stop codons, leading to the inclusion of 3′ untranslated regions (3′ UTRs) within genes. We classified changes in the position of stop codons in closely related Saccharomyces species and in a mouse/rat comparison as either additions to or subtractions from coding regions. In both cases, the position of stop codons is highly labile, with more subtractions than additions found. The subtraction bias may be balanced by the input of new coding regions through gene duplication. Saccharomyces shows less stop codon lability than rodents, probably due to greater selective constraint. A higher proportion of 3′ UTR incorporation events preserve frame in Saccharomyces. This higher proportion is consistent with the action of the [PSI+] prion as an evolutionary capacitor to facilitate 3′ UTR incorporation in yeast.