Spontaneous Mutation & DNA Repair Group
Biochemistry & Genetics of Mutagenesis & DNA Repair
John W. Drake, Ph.D.
Principal Investigator - Retired
The Spontaneous Mutation & DNA Repair Group explores diverse aspects of the mutation process using both traditional and exotic organisms.
Collections of spontaneous mutants typically contain more isolates carrying multiple mutations than are predicted if all the mutations were distributed at random. These clusters are likely to arise by a process of transient hypermutability and to contribute to adaptive evolution, microbial pathogenesis, and perhaps carcinogenesis. We are currently exploring the genetic and biochemical mechanisms that generate such clusters using models systems. For instance, a currently pressing question is whether such clusters are limited in extent to one or a few adjacent genes, or can target widely separated genes. This is a technically challenging measurement because it requires screening large numbers of organisms (on the order of 1012 per event), but can be undertaken using a bacterium such as Escherichia coli.
Paradoxically, the organismal group with the highest mutation rate, the riboviruses (including such notorious human pathogens as influenza virus) is also the group for which the least is known about the kinds of mutations that typically arise, and for which only approximate mutation-rate estimates are available. After many years of effort, a moderately tractable model system has been developed using the bacteriophage Qß, which infects the well-studied host E. coli.
Major areas of research:
- Genetic and biochemical mechanisms that generate mutation clusters
- Mutation rates in RNA viruses
John W. Drake, Ph.D., heads the Spontaneous Mutation and DNA Repair Group within the Laboratory of Molecular Genetics. He received his Ph.D. from the California Institute of Technology in 1958 and joined the NIEHS in 1977.