ABSTRACT
In the 1950s, RNA emerged as the link between gene and protein. Large ribonucleoprotein complexes, termed ‘ribosomes’, were identified as the sites of protein synthesis. Proteins were shown to be linear polymers of amino acids and the first three-dimensional structures of proteins solved. The order of nucleotides in the DNA was hypothesized and confirmed to instruct the sequence of amino acids in proteins via a temporary (‘messenger’) RNA copy of the gene and adaptor ‘transfer RNAs’ that connected the two. The triplet ‘genetic code’ that specifies the order of amino acids was determined, including translational start and ‘stop’ codons. Mutations were found to alter the amino acid (‘missense’) or prematurely terminate protein synthesis (‘nonsense’). The lactose utilization (lac) operon of Escherichia coli was shown to specify three enzymes and a regulatory locus, initially posited to express an RNA, but subsequently found to encode a DNA-binding repressor protein that is displaced upon lactose binding. The lac operon became the archetypal textbook conception of genes as co-linear segments of protein-coding information controlled by adjacent ‘cis-acting promoter’ sequences that bind regulatory proteins, called ‘transcription factors’. Although the concept of ‘genetic programming’ was emerging, the conclusion that genetic information is transacted primarily by proteins became entrenched, a reflection of the mechanical zeitgeist of the age, and assumed to be true both for bacteria and developmentally complex plants and animals. The newly minted ‘Central Dogma’ of molecular biology asserted that ‘DNA makes RNA makes proteins’, with RNA tacitly but firmly relegated to an ephemeral intermediate. All that remained, it seemed, was to flesh out the detail.
