KEY CONCEPTS:
- Changes in the universal genetic code have occurred in some species.
- They are more common in mitochondrial genomes, where a phylogenetic tree can be constructed for the changes.
- In nuclear genomes, they are sporadic and usually affect only termination codons.
The universality of the genetic code is striking, but some
exceptions exist. They tend to affect the codons involved in initiation or
termination and result from the production (or absence) of tRNAs representing
certain codons. The changes found in principal (bacterial or nuclear) genomes
are summarized in Figure 7.10.
Almost all of the changes that allow a codon to represent an
amino acid affect termination codons:
- In the prokaryote Mycoplasma capricolum, UGA is not used for
termination, but instead codes for tryptophan. In fact, it is the predominant
Trp codon, and UGG is used only rarely. Two Trp-tRNA species exist, with the
anticodons UCA
(reads UGA and UGG) and CCA
(reads only UGG).
- Some ciliates (unicellular protozoa) read UAA and UAG as glutamine instead of termination signals. Tetrahymena thermophila, one of the ciliates, contains three tRNAGlu species. One recognizes the usual codons CAA and CAG for glutamine, one recognizes both UAA and UAG (in accordance with the wobble hypothesis), and the last recognizes only UAG. We assume that a further change is that the release factor eRF has a restricted specificity, compared with that of other eukaryotes.
- In another ciliate (Euplotes octacarinatus), UGA codes for cysteine. Only UAA is used as a termination codon, and UAG is not found. The change in meaning of UGA might be accomplished by a modification in the anticodon of tRNACys to allow it to read UGA with the usual codons UGU and UGC.
- The only substitution in coding for amino acids occurs in a yeast (Candida), where CUG means serine instead of leucine (and UAG is used as a sense codon).
Acquisition of a coding function by a termination codon
requires two types of change: a tRNA must be mutated so as to recognize the
codon; and the class 1 release factor must be mutated so that it does not
terminate at this codon.
The other common type of change is loss of the tRNA that
responds to a codon, so that the codon no longer specifies any amino acid. What
happens at such a codon will depend on whether the termination factor evolves to
recognize it.
All of these changes are sporadic, which is to say that they
appear to have occurred independently in specific lines of evolution. They may
be concentrated on termination codons, because these changes do not involve
substitution of one amino acid for another. Once the genetic code was
established, early in evolution, any general change in the meaning of a codon
would cause a substitution in all the proteins that contain that amino acid. It
seems likely that the change would be deleterious in at least some of these
proteins, with the result that it would be strongly selected against. The
divergent uses of the termination codons could represent their "capture" for
normal coding purposes. If some termination codons were used only rarely, they
could be recruited to coding purposes by changes that allowed tRNAs to recognize
them.
Exceptions to the universal genetic code also occur in the
mitochondria from several species. Figure 7.11 constructs
a phylogeny for the changes. It suggests that there was a universal code that
was changed at various points in mitochondrial evolution. The earliest change
was the employment of UGA to code for tryptophan, which is common to all
(non-plant) mitochondria (for review see Osawa et al., 1992).
Some of these changes make the code simpler, by replacing
two codons that had different meanings with a pair that has a single meaning.
Pairs treated like this include UGG and UGA (both Trp instead of one Trp and one
termination) and AUG and AUA (both Met instead of one Met and the other
Ile).
Why have changes been able to evolve in the mitochondrial
code? Because the mitochondrion synthesizes only a small number of proteins
(~10), the problem of disruption by changes in meaning is much less severe.
Probably the codons that are altered were not used extensively in locations
where amino acid substitutions would have been deleterious. The variety of
changes found in mitochondria of different species suggests that they have
evolved separately, and not by common descent from an ancestral mitochondrial
code.
According to the wobble hypothesis, a minimum of 31 tRNAs
(excluding the initiator) are required to recognize all 61 codons (at least 2
tRNAs are required for each codon family and 1 tRNA is needed per codon pair or
single codon). But an unusual situation exists in (at least) mammalian
mitochondria in which there are only 22 different tRNAs. How does this limited
set of tRNAs accommodate all the codons?
The critical feature lies in a simplification of
codon-anticodon pairing, in which one tRNA recognizes all four members of a
codon family. This reduces to 23 the minimum number of tRNAs required to respond
to all usual codons. The use of AGAG for termination
reduces the requirement by one further tRNA, to 22.
In all eight codon families, the sequence of the tRNA
contains an unmodified U at the first position of the anticodon. The remaining
codons are grouped into pairs in which all the codons ending in pyrimidines are
read by G in the anticodon, and all the codons ending in purines are read by a
modified U in the anticodon, as predicted by the wobble hypothesis. The
complication of the single UGG codon is avoided by the change in the code to
read UGA with UGG as tryptophan; and in mammals, AUA ceases to represent
isoleucine and instead is read with AUG as methionine. This allows all the
nonfamily codons to be read as 14 pairs.
The 22 identified tRNA genes therefore code for 14 tRNAs
representing pairs, and 8 tRNAs representing families. This leaves the two usual
termination codons UAG and UAA unrecognized by tRNA, together with the codon
pair AGAG. Similar rules are followed in the mitochondria
of fungi (for review see Fox, 1987).