Dual consequence of mutation in the dihydrofolate reductase gene of Diplococcus pneumoniae

Ten mutations have been identified at four genetically linked sites on the D. pneumoniae chromosome which determine an increase in the amount of dihydrofolate reductase and severely alter the structure as well. Mutant enzyme levels are increased as much as 60-fold over the wild-type. The mutant enzymes are markedly altered in the ability to bind the antifolate, amethopterin, and in respect to their thermostability properties. These findings may be pertinent to the question of the role of the structural gene itself in setting limits of synthesis of the gene product.