The
structure of DNA was determined in 1953 by Watson, Crick, and Franklin, with
strands of the double helix consisting of four nucleotides: adenine (A),
thymine (T), cytosine (C), and guanine (G); in RNA, uracil (U) replaces T. But
how was the genetic information contained in the DNA molecule translated to the
biosynthesis of a protein?
The
Russian physicist George Gamow postulated that a three-letter nucleotide
(codon) could define up to sixty-four amino acids, more than sufficient to code
for all twenty amino acids used to build proteins. In 1961, Marshall Nirenberg,
with J. Heinrich Matthaei at the National Institutes of Health, sought to
determine what amino acid would be formed after a single nucleotide was added
to a reaction mixture. UUU produced the amino acid phenylalanine, cracking the
first letter in the genetic code. Shortly thereafter, the addition CCC was
found to yield proline. Har Gobind Khorana at the University of
Wisconsin-Madison produced more complex sequences composed of repeated
twonucleotide sequences, the first of which was UCUCUC, read as
serine-leucine-serine-leucine . . .; subsequently, the remainder of the codons
were determined.
 |
| This image depicts the relationship between the codon (the three-letter nucleotide consisting of adenine, thymine, cytosine, and guanine or uracil) and the encoding of amino acids. |
In
1964, Robert Holley, at Cornell University, discovered and established the
chemical structure of transfer RNA (tRNA), thus providing the link between the
role of messenger RNA (mRNA) and ribosomes. The information needed to make a
protein is first attached to tRNA and then translated to messenger mRNA in a
ribosome. Each tRNA only recognizes one set of three nucleotides in mRNA, and
tRNA binds to only one of the twenty amino acids. A protein is formed by the
addition of one amino acid at a time. Nirenberg, Khorana, and Holley were
jointly awarded the 1968 Nobel Prize. Apart from variations, the genetic codes
used by all forms of life are very similar. Based on the theory of evolution,
the genetic code was established very early in the history of life.
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