A HUMBLE yeast that has dared to rewrite the 鈥渦niversal鈥� genetic language of
DNA is more resistant to stress as a result, researchers say. Their work reveals
a fast-track mechanism that organisms can use to evolve, raising new fears about
the speed with which harmful microbes can develop resistance to drugs.
Biochemists are taught that all living things employ a common language or
code when they read information in DNA and use it as a blueprint for assembling
proteins. Francis Crick, the co-discoverer of DNA鈥檚 structure, suggested in 1968
that organisms would die if they developed deviations in this language, as
proteins would be mis-assembled and the organism would be too freakish and
鈥渦nfit鈥� to survive.
But in 1993, Manuel Santos and Mick Tuite at the University of Kent showed
that the code is not universal. The team discovered deviations from the norm in
a strain of Candida albicans, the yeast that causes thrush and other
fungal infections. They found that proteins from the yeast often contain the
amino acid serine where leucine would have been expected. Now Santos and his
colleagues have shown that this makes the yeast 鈥渇itter鈥� than its more
conventional relatives.
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Cells assemble proteins by reading the recipes encoded in messenger RNA
(mRNA), a single-stranded copy of the original DNA. The cell works out which
amino acid to add next by reading 鈥渃odons鈥濃�攖riplets of adenine (A),
guanine (G), cytosine (C) and uracil (U), the four bases of mRNA.
The yeast strain isolated by the Kent team broke the rules by misreading the
codon CUG, which usually corresponds to the amino acid leucine. The yeast often
added serine to the chain instead.
Santos and his colleagues have pinned the blame on a mutant form of transfer
RNA (tRNA), a molecular shuttle that delivers amino acids to the growing protein
chain. They transplanted the mutant gene for the tRNA from C. albicans
into baker鈥檚 yeast (Saccharomyces cerevisiae), which is easier to grow
in the lab. The mutant tRNA鈥檚 molecular architecture meant that it could load
serine as well as leucine into the growing protein.
As a result, the altered S. cerevisiae could potentially load 50 000
serines into proteins instead of leucine, which should have spelt catastrophe
for the baker鈥檚 yeast. Instead, it tolerated stresses such as high temperatures,
heavy metals, powerful oxidising agents and a laboratory antibiotic called
cyclohexamide. Natural baker鈥檚 yeast died when exposed to the same stresses.
鈥淧eople said such changes would be lethal, but we鈥檝e shown it鈥檚 advantageous,鈥�
says Santos, who is now at the University of Aveiro in Portugal.
鈥淲e think that the serine-rich proteins are detected by molecular sensors in
the yeast which trigger a general stress response,鈥� says Santos. This would
explain how the yeast becomes so resistant to the stresses. The team鈥檚 work will
appear in Molecular Microbiology.
Variants of the genetic code could be widespread. 鈥淲e believe there are many
more genetic code changes, as they provide accelerated development of new
phenotypes,鈥� says Santos. He adds that microorganisms might use it as a
fast-track ploy for developing traits such as antibiotic resistance.
