A cross-eyed geneticist’s view V. How Sydney Brenner, Leslie Barnett, Eugene Katz, and Francis Crick inferred that UGA is a nonsense codon
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Introduction: the unique genetics of T4 rII
UGA was the last of the 64 codons of the genetic code to be assigned. Until then, 61 codons were shown to code for one or another of the 20 amino acids. Two codons, UAG (amber) and UAA (ochre), were established to not code for any amino acid, and hence were designated as ‘nonsense’ codons. Only UGA remained unallocated. To show that UGA also is a nonsense codon, Brenner et al. (1967) used three ‘genetics’ resources: (1) The chemical mutagens 2-aminopurine (2-AP) and hydroxylamine (HA). The former induces G-C to A-T and A-T to G-C transition mutations, whereas the latter induces only G-C to A-T transitions. (2) The amber- and ochre-suppressor strains of E. coliK12 that contain suppressor tRNAs that insert an ‘acceptable’ amino acid at, respectively, UAG and UAA codons in the mRNA, and thus suppress the phenotypes of mutations to these codons, and (3) the vast collection of bacteriophage T4 rIIA and rIIB gene mutants amassed by Seymour Benzer...
Keywords2-Aminopurine anomalous minutes bacteriophage T4 hydroxylamne nonsense suppression rIIA and rIIB cistrons
I thank Gene Katz, Vidyanand Nanjundiah, K. Dharmalingam, Sharat Chandra, and Dipankar Chatterji for comments and suggestions. The article was developed from my lecture (‘Brenner’s elegant nonsense’) to commemorate the life and research of Sydney Brenner (13 January 1927 – 5 April 2019) in the First Hy-Sci Conference in Hyderabad. I am an Indian National Science Academy Senior Scientist in the Centre for DNA Fingerprinting and Diagnostics, Hyderabad, and an Honorary Visiting Scientist at the Centre for Cellular and Molecular Biology, Hyderabad. This article is dedicated to the memory of John A. Whitbread.