1. We only see mutations that have large effects.
2. Large effects are more likely to be deleterious.
3. Small mutations are also likely to be deleterious.
4. We have few examples of small deleterious mutations.
5. Beneficial mutations are most likely to be small in effect.
6. We are unlikely to find many cases of beneficial mutations.
Asking to see beneficial mutations is like asking to see minor bad ones. We donÃ¢â‚¬â„¢t see them because their effect is likely to be small. Sickle cell anaemia is used because it is a major effect.
Here is another and in this case, because of the beauty of the experiment, it is empirical and repeatable.
In 2008, Lenski and his collaborators reported on a particularly important adaptation that occurred in one of the twelve populations: the bacteria evolved the ability to utilize citrate as a source of energy. Wild type E. coli cannot transport citrate across the cell membrane to the cell interior (where it could be incorporated into the citric acid cycle) when oxygen is present. The consequent lack of growth on citrate under oxic conditions is considered a defining characteristic of the species that has been a valuable means of differentiating E. coli from pathogenic Salmonella. Around generation 33,127, the experimenters noticed a dramatically expanded population-size in one of the samples; they found that there were clones in this population that could grow on the citrate included in the growth medium to permit iron acquisition. Examination of samples of the population frozen at earlier time points led to the discovery that a citrate-using variant had evolved in the population at some point between generations 31,000 and 31,500. They used a number of genetic markers unique to this population to exclude the possibility that the citrate-using E. coli were contaminants. They also found that the ability to use citrate could spontaneously re-evolve in populations of genetically pure clones isolated from earlier time points in the population's history. Such re-evolution of citrate utilization was never observed in clones isolated from before generation 20,000. Even in those clones that were able to re-evolve citrate utilization, the function showed a rate of occurrence on the order of once per trillion cells. The authors interpret these results as indicating that the evolution of citrate utilization in this one population depended on an earlier, perhaps non-adaptive "potentiating" mutation that had the effect of increasing the rate of mutation to citrate utilization to an accessible level (with the data they present further suggesting that citrate utilization required at least two mutations subsequent to this "potentiating" mutation). More generally the authors suggest that these results indicate (following the argument of Stephen Jay Gould) "that historical contingency can have a profound and lasting impact" on the course of evolution.