Restriction endonucleases, simian virus 40, and the new genetics.

Introduction Some 3.5 years ago the study of heredity took a chemical turn when Avery and his colleagues discovered that deoxyribonucleic acid-DNA-is the " transforming principle " that converts bacteria from one genotype to another. Watson and Crick's structural model of DNA then provided the basis for investigating its role as the hereditary material. There followed rapid advances in the biochemistry of DNA replication, gene expression, and regulation of genes. Recently, fresh impetus has been given to the study of genetic mechanisms, particularly in higher organisms, by several methodological developments that have opened a new approach to the analysis of chromosomes: site-specific cleavage of DNA by restriction endonucleases and electrophoretic fractionation of the resulting fragments ; recombination, cloning, and amplification of DNA segments from any source; rapid methods for determining the nucleotide sequence of DNA; site-directed in vitro mutagenesis; synthesis of polydeoxynucleotides of predetermined sequence; and the ability to introduce cloned, functioning genes into prokaryotic or eukaryotic cells. As a result of these developments even chromosomes which are largely inaccessible to classical genetic methods can now be analysed piece by piece in chemical detail. Genes and signals can be altered at pre-selected sites, and the functional effect of such alterations determined. And active, synthetic genes can be constructed in vitro by recombination or by chemical synthesis.