Biochemistry & Genetics of Mutagenesis & DNA Repair
John W. Drake, Ph.D.
Principal Investigator and Chief, Laboratory of Molecular Genetics
Tel (919) 541-3361
Fax (919) 541-7613
P.O. Box 12233
Mail Drop E3-01
Research Triangle Park, North Carolina 27709
The Spontaneous Mutation & 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 contribute to carcinogenesis, microbial pathogenesis, ribovirus stability, and adaptive evolution. The group is beginning to explore the genetic and biochemical mechanisms that generate such clusters, starting with an RNA bacteriophage, the replicative DNA polymerase gp43 used by bacteriophage RB69, and the human DNA-repair polymerase β.
Rates of spontaneous mutation fall into a few distinct categories that probably represent evolutionary balances between the deleterious consequences of most mutations and the investment costs of further reducing mutation rates. Most DNA-based microbes examined to date produce about one mutation per 300 chromosome replications. Higher eukaryotes have the same or a slightly higher rate, so that rates per sexual generation can approach the maximum compatible with life. RNA-virus mutation rates approach 0.1–1 per chromosome replication. However, an earlier study recorded a high proportion of clusters in an RNA virus and suggested that a majority of viruses had a low mutation frequency while a minority had a high frequency. Thus, RNA virus populations may evolve in two ways, sometimes using low mutation rates and sometimes high rates.
Major areas of research:
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.