Page 119 - Genetics_From_Genes_to_Genomes_6th_FULL_Part2

278 Chapter 8 Gene Expression: The Flow of Information from DNA to RNA to Protein

codons appear in frame, translation stops. As an example of that differed from the triplet UAG by a single nucleotide.
how investigators established this fact, consider the case of These data suggested that each m mutant had a point muta-
poly-GUAA (review Fig. 8.5b). This mRNA will not gen- tion that changed a codon for an amino acid into the stop
erate a long polypeptide because in all possible reading codon UAG. Such a mutation is called a nonsense mutation
frames, it contains the stop codon UAA. because it changes a codon that signifies an amino acid (a
Sydney Brenner helped establish the identities of the sense codon) into one that does not (a nonsense codon). (It
stop codons in an alternative way, through ingenious experi- was not a coincidence that all of the truncation mutants had
ments involving point mutations in a T4 phage gene named nonsense mutations where a codon was a changed to a par-
m, encoding a protein component of the phage head capsule. ticular stop codon—in this case UAG. Problem 56 at the end
As shown in Fig. 8.8a, Brenner determined that certain mu- of this chapter explains why this was the case.)
tant alleles (m –m ) encoded truncated polypeptides that Brenner later established that a fine structure map of mu-
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were shorter than the wild-type M protein. Brenner found tations m –m corresponds in a linear manner to the size of
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that the final amino acid at the C terminus in each of the the truncated polypeptide chains (Fig. 8.8b). It makes sense
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truncated proteins would have been followed in the normal, that the M protein encoded by m , for example, is shorter than
full-length protein by an amino acid specified by a codon that encoded by m because the m nonsense mutation is
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5
5
closer to the beginning of the reading frame than m .
Brenner also isolated analogous sets of nonsense muta-
Figure 8.8 Sydney Brenner’s experiment showing that
+
UAG is a stop signal. (a) The T4 phage m gene encodes a tions that defined UAA and UGA as stop codons. For histor-
polypeptide M whose amino acids are shown with blue circles. ical reasons, researchers often refer to UAG as the amber
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Mutant alleles m –m direct synthesis of truncated M proteins (black codon, UAA as the ochre codon, and UGA as the opal codon.
circles). In the wild-type M protein, the amino acid that would follow The historical basis of this nomenclature is the last name of
the final amino acid in each truncated protein is encoded by a triplet one of the early investigators—Bernstein—which means
that differs from UAG by a single nucleotide. (b) The genetic map amber in German; ochre and opal derive from their similarity
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positions of the m –m mutations are colinear with the sizes of the
corresponding truncated M proteins. with amber as semiprecious materials.
(a) Nonsense mutations
Phage M polypeptide length
gene CAG The Genetic Code: A Summary
Gln
m + The genetic code is a complete, unabridged dictionary
m 1 equating the four-letter language of the nucleic acids with
UAG the 20-letter language of the proteins. The following list
AAG summarizes the code’s main features:
Lys
m + 1. Triplet codons: As written in Fig. 8.2, the code shows
m 2 the 5′-to-3′ sequence of the three nucleotides in each
UAG mRNA codon; that is, the first nucleotide depicted is
GAG at the 5′ end of the codon.
Gly
m + 2. The codons are nonoverlapping. In the mRNA
m 3 sequence 5′ GAAGUUGAA 3′, for example, the
UAG first three nucleotides (GAA) form one codon;
UAU nucleotides 4 through 6 (GUU) form the second; and
Tyr so on. Each nucleotide is part of only one codon.
m + 3. The code includes three stop, or nonsense, codons:
m 4 UAG, UAA, and UGA. These codons do not usually
UAG
UGG encode an amino acid and thus terminate translation.
Trp 4. The code is degenerate, meaning that more than one
m + codon may specify the same amino acid. The code
m 5 is nevertheless unambiguous because each codon
UAG specifies only one amino acid.
UCG 5. The cellular machinery scans mRNA from a fixed
Ser
m + starting point that establishes a reading frame. As we
m 6 will see later, the nucleotide triplet AUG, which spec-
UAG ifies the amino acid methionine wherever it appears in
the reading frame, also serves as the initiation codon,
(b) Fine structure map marking where in an mRNA the code for a particular
m 6 m 5 m 4 m 3 m 2 m 1
polypeptide begins.