Co-linearity of the gene with the polypeptide chain [first study to show co-linearity]

Sarabhai, A. S.; Stretton, A. O. W., Brenner, Sydney (1927- ); and Bolle, A. Co-linearity of the gene with the polypeptide chain. Offprint from Nature 201 (1964). [4]pp. Text illustrations. 280 x 218 mm. Without wrappers as issued. Light browning, minor creasing, small marginal tears, otherwise very good. First Separate Edition. Brenner and his colleagues performed the first study to show co-linearity; i.e., that there is a simple congruence between the amino acid sequence of a protein and the nucleotide sequence of the gene determining that protein. Brenner and his team were working with "nonsense" mutants, called amber mutants, that terminated protein synthesis in E. coli genes. "The presence of random nonsense mutants would therefore yield multiple random protein fragments of different sizes. . . . [W]e now suddenly realized that since we had all these amber mutants in this gene we could give a topological proof of co-linearity. And we wouldn't have to do any protein sequencing! The only assumption we would have to make is that the protein is always read from the same end, which seemed a very reasonable one. So in 1964 we published a paper which proved that the gene and the protein were co-linear by an argument that was totally unexpected at that time. We showed that as the amber mutations moved further and further to the right in the position of the gene, we got progressively more and more of the protein made :(Brenner, My Life, p. 103). Co-linearity means that changes in DNA sequence can produce changes in protein sequence at corresponding positions. Working independently, Charles Yanofsky and his colleagues were also able to show co-linearity; "it was the Yanofsky work on tryptophan synthetase that was to provide the specifics of amino acid substitutions with gene mutations" (Brock, p. 312). .…