The average accuracy of protein synthesis in reticulocytes from several mammalian species does not correlate with longevity potential from 13 to 90 years. Isoleucine incorporation into highly purified hemoglobin chains which contain no genetically coded isoleucine was used as a direct test of protein synthesis accuracy. Since isoleucine can be incorporated into these molecules by mutations in a few cells as well as errors in most cells, the constant level of isoleucine substitution may also show that the mutation rates are not dramatically different among these species. Isoleucine substitutions in hemoglobin can be used to estimate mutations only above the level of errors, which may be as low as 1/1,000,000, but the probability of seeing a few mutant clones at any time is dependent on the number of stem cells producing reticulocytes. The number of stem cells being expressed is a reflection of the number of cell divisions per clone. If the number of cell divisions per clone is 30 or less, then isoleucine substitutions would increase when the mutation accumulation rose above 30 per million for the mutation to isoleucine at any position in the alpha or beta chain.
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