Evolution__3rd_Edition

188 PART 2 / Evolutionary Genetics
In microbes, codon usage matches
tRNA abundance, ...
. . . and the match is better for
genes that are expressed more
Table 7.7
Relative frequencies of six leucine codons in genes of Escherichia coli and yeast (Saccharomyces
cerevisiae). The genes are divided into high usage genes and low usage genes: high usage genes are
frequently transcribed, low usage genes are rarely transcribed. Note (i) codon biases are larger for
highly used genes than low use genes, and (ii) the codon biases differ between the two species. The
numbers are relative frequencies: they add up to six. A relative frequency of less than one means the
codon is rarer than expected; of more than one means it is commoner than expected. Modified from
Sharp et al. (1995).
E. coli S. cerevisiae
Leucine codon High Low High Low
UUA 0.06 1.24 0.49 1.49
UUG 0.07 0.87 5.34 1.48
CUU 0.13 0.72 0.02 0.73
CUC 0.17 0.65 0.00 0.51
CUA 0.04 0.31 0.15 0.95
CUG 5.54 2.20 0.02 0.93
hydrogen bonds while AT has only two. Natural selection might work against GC to
AT changes in regions of the DNA that need to be stably bonded. Secondly, different
transfer RNAs are used by the different synonymous codons. (There are fewer kinds of
tRNA than codons because of the phenomenon of “wobble.” For some pairs of codons,
one kind of tRNA can bind them both.) The different tRNAs have a certain frequency
distribution in the cells: some tRNAs, among a synonymous set, are more frequent
than others. Figure 7.8 shows tRNA abundances in the lower half (gray columns). A
change in E. coli DNA from a CUG codon to a CUA codon might be selected against.
The change might reduce the efficiency of protein synthesis, because the cell contains
little leucine tRNA for the CUA codon.
Figure 7.8 shows that the codon frequencies match the tRNA frequencies. The
pattern makes sense if the two distributions evolve together, and changes from common
to rare codons reduce translational efficiency. The argument can be strengthened.
Some genes in bacteria and yeast are frequently translated. These can be called “high
use” genes. Other genes are less often translated, and can be called “low use” genes. The
efficiency of protein synthesis probably matters more for high use than low use genes.
Table 7.7 shows that codon biases are much greater in high use than in low use genes.
Thus, in high use genes natural selection works against codon changes. The cell benefits
from having more of the codons corresponding to abundant tRNAs. In low use genes,
changes are disadvantageous and the codon frequencies evolve by drift to be more
equal. The difference between high use and low use genes in Table 7.7 is difficult to
explain by mutation pressure.
At least in unicellular organisms, codon biases are thought to be caused more by
selective constraints than mutation pressure. Evolution in synonymous sites still fits
..