DNA to Protein Translator

Translation maps nucleotide triplets onto amino acids. With four bases read three at a time there are 64 codons for 20 amino acids plus termination, so the code is degenerate: 61 sense codons and three stop signals, UAA, UAG, and UGA. AUG serves double duty as the codon for methionine and as the initiation signal. Degeneracy is not random. Most synonymous codons differ only at the third position, and the code groups chemically similar amino acids so that many single-base substitutions are silent or conservative, which buffers the effect of point mutations. Converting DNA to mRNA replaces thymine with uracil; the coding strand sequence and the mRNA are otherwise identical. Because codons are read without punctuation, the choice of starting nucleotide defines the reading frame, and a sequence has three forward frames plus three more on the reverse complement. Shifting by one base produces an entirely different peptide, which is why an insertion or deletion that is not a multiple of three is so damaging. An open reading frame is a stretch running from an AUG to an in-frame stop with no interruption. In random sequence a stop appears roughly once every 21 codons, so ORFs shorter than about 100 codons occur frequently by chance and carry little evidence of being genuine genes. Two caveats limit direct translation of any sequence: eukaryotic genomic DNA contains introns that must be spliced out before the reading frame is meaningful, so translation should be applied to cDNA, and the standard code is not universal. Vertebrate mitochondria read UGA as tryptophan and AGA and AGG as stop, and several ciliates reassign UAA and UAG to glutamine, so the correct translation table must match the source organism and compartment.

That the code must be triplet-based was argued theoretically before it was read. Francis Crick proposed the adaptor hypothesis in 1958, predicting a molecule that would carry an amino acid and recognize the nucleic acid template, and in 1961 Crick, Leslie Barnett, Sydney Brenner, and Richard Watts-Tobin used acridine-induced frameshift mutations in bacteriophage T4 to show that the code is read in non-overlapping groups of three from a fixed starting point. The assignments themselves were determined experimentally beginning the same year, when Marshall Nirenberg and Heinrich Matthaei at the National Institutes of Health added a synthetic poly-uracil template to a cell-free extract and obtained polyphenylalanine, establishing UUU as phenylalanine. Severo Ochoa contributed further copolymer work, and Har Gobind Khorana synthesized defined repeating sequences that resolved ambiguities. The decisive method was the triplet binding assay developed by Nirenberg and Philip Leder in 1964, in which individual trinucleotides were tested for their ability to bind specific charged transfer RNAs to ribosomes; with it the full table was completed by 1966. Nirenberg, Khorana, and Robert Holley, who had sequenced alanine transfer RNA, shared the 1968 Nobel Prize in Physiology or Medicine. The code was long assumed universal until Barrell, Bankier, and Drouin reported in 1979 that human mitochondria use different assignments, and the National Center for Biotechnology Information now maintains a numbered set of translation tables covering the standard code and its documented variants.