| Abstract: |
Protein dysfunction is, to some extent, in the eye of the beholder. The general tenet of neo-Darwinian biology is that evolution proceeds by the trials and errors of successive mutations. For many characteristics of living organisms it can be quite hard to work out in detail the workings of evolution from the mere inspection of the final products as we see them today. However, when dealing with a specific protein, two basic criteria can be very helpful: (i) the specific biochemical function of that protein; and (ii) the phenotypic consequences of minute changes in that protein, such as those produced by point mutations in the respective gene. The case of glucose 6-phosphate dehydrogenase (G6PD) is especially favourable in this respect, because it is an enzyme with exquisite specificity, and because numerous point mutations in the human G6PD gene produce distinctive phenotypes, which have been well characterized thanks to the attention that patients with haemolytic anaemias have received from haematologists over the past century. Thus, in the case of human G6PD we can clearly define protein dysfunction as a minor or major failure in the catalytic properties or in the stability of the enzyme, which makes a dent in the features which had been finely tuned by the evolutionary process to a level which we regard as optimal. © 1997 by Taylor & Francis Group, LLC. |
