Risk assessment: the importance of genetic polymorphisms in man

Spontaneous mutation was greatly increased in a localized region of the chromosome of Haemophilus influenzae, but not at other loci, by a nov gene mutation called novC that increased DNA supercoiling. Another nov gene mutation, called novD, decreased spontaneous mutation in the same localized region and depressed DNA supercoiling. Both mutations, which code for the gyrase B subunit, have been cloned, and the cloned versions also altered mutagenesis and supercoiling in a similar fashion as the two mutations on the chromosome, although novC on the plasmid caused somewhat less mutation than on the chromosome. We postulate that the effects of the gyrase B mutations on the chromosome result from their effects on supercoiling because of increased gyrase near its site of production. The fact that the novC on a plasmid does not cause mutagenesis except in the same localized region that is altered by this mutation on the chromosome, is difficult to explain. One possibility is that there is a complex of proteins in this region which is necessary for the effects on supercoiling and thus, also on mutagenesis.