carries out protein synthesis by reading the mRNA sequence that lies immediately downstream of the
“start codon” (typically AUG). The codons are then read sequentially, from 5- to 3on the mRNA, until
the ribosome reaches a “stop codon” (UAA, UAG, or UGA). Each codon is “read,” or decoded, by the for-
mation of Watson–Crick pairings with the anticodonloop of specific tRNAs that carry cognate amino
acidsinto the heart of the ribosome. The sequential arrangement of triplet nucleotides is called the read-
ing frame, which can be disrupted by certain types of DNA mutations that alter the mRNA coding
sequence and produce nonsense proteins. However, certain mRNAs actually encode multiple proteins
through the ribosomal decoding of alternate reading frames (recoding).^52
While the genetic code is remarkably universal from bacteria to higher organisms, there are important
exceptions, particularly in mitochondria and in certain lower eukaryotes.^46 For example, the leucine codon
(CUG) in Candidayeasts has been reassignedto encode serine, and the UAA and UAG stop codons have
been reassigned to glutamine in diverse ciliates and green algae. In bacteria and eukaryotes, UGA (normally
a stop) is often placed in a context that permits pairing with the unusual tRNAsecmolecule, by which it is
used to encode the 21st amino acid, selenocysteine.^53 Modified nucleotides in the anticodon of tRNA can
lead to exceptions in the genetic code (such as lysidine, see Section 7.2.4), and even to the incorporation
of rare amino acids.
While triplet pairings between tRNA and mRNA have remained a remarkably robust format for infor-
mation transfer in all organisms, the genetic code has now been expanded artificially in an effort to incorp-
orate unnatural amino acids into proteins and, potentially, to generate entire organisms with new
properties. Major success in this area has been achieved by using alternative triplet codons in order to
specify unnatural tRNAs that carry modified amino acids.^54 In some cases, new forms of base pairing have
been used to generate entirely novel codons, and there have been efforts to expand the genetic code from
triplet to quadruplet format.
274 Chapter 7
Figure 7.25 The genetic code. The 64 codons are divided into 16 four-codon boxes. The four codons of a codon box
differ in their 3-terminal nucleotide. Red shows where an amino acid is specified by all four codons of
a codon box, pink shows where an amino acid is specified by two (or in one case three) of the four
codons, and grey shows where an amino acid is specified by a single codon