The evolutionary design of error-rates, and the fast fixation enigma.

Genetic and non-genetic error-rates are analyzed in parallel for a lower and a higher organism (E. coli and man, respectively). From the comparison of mutation with fixation rates, contrasting proposals are made, concerning the arrangement of error-rates in the two organisms. In E. coli, reproduction is very conservative, but genetic variability is high within populations. Most mutations are discarded by selection, yet single mutational variants of a gene have, on average, little impact on fitness. In man, the mutation rate per generation is high, the variability generated in the population is comparatively low, and most mutations are fixed by drift rather than selection. The variants of a gene are in general more deleterious than in E. coli. There is a discrepancy in the published mutation rates: the rate of mutation fixations in human populations is twice or four times higher than the individual rate of mutation production, a feature which is not consistent with current population genetics models. Two, not mutually exclusive, hypotheses may explain this 'fast fixation enigma': (i) Mutation rates have substantially decreased in recent human evolution and (ii) A substantial fraction of the fixed mutations were generated in a process-such as gene conversion-that violates the principle of independence of mutation events.