Changes in expression patterns may occur when organisms are presented with new environmental challenges, for example following migration or genetic changes. To elucidate the mechanisms by which the translational machinery adapts to such changes, we perturbed the tRNA pool of Saccharomyces cerevisiae by tRNA gene deletion. We then evolved the deletion strain and observed that the genetic adaptation was recurrently based on a strategic mutation that changed the anticodon of other tRNA genes to match that of the deleted one. Strikingly, a systematic search in hundreds of genomes revealed that anticodon mutations occur throughout the tree of life. We further show that the evolution of the tRNA pool also depends on the need to properly couple translation to protein folding. Together, our observations shed light on the evolution of the tRNA pool, demonstrating that mutation in the anticodons of tRNA genes is a common adaptive mechanism when meeting new translational demands.
Genes contain the blueprints for the proteins that are essential for countless biological functions and processes, and the path that leads from a particular gene to the corresponding protein is long and complex. The genetic information stored in the DNA must first be transcribed to produce a messenger RNA molecule, which then has to be translated to produce a string of amino acids that fold to form a protein. The translation step is performed by a molecular machine called the ribosome, with transfer RNA molecules bringing the amino acids that are needed to make the protein.
The information in messenger RNA is stored as a series of letters, with groups of three letters called codons representing the different amino acids. Since there are four letters—A, C, G and U—it is possible to form 64 different codons. And since there are only 20 amino acids, two or more different codons can specify the same amino acid (for example, AGU and AGC both specify serine), and two or more different transfer RNA molecules can take this amino acid to the ribosome. Moreover, some codons are found more often than others in the messenger RNA molecules, so the genes that encode the related transfer RNA molecules are more common than the genes for other transfer RNA molecules.
Environmental pressures mean that organisms must adapt to survive, with some genes and proteins increasing in importance, and others becoming less important. Clearly the relative numbers of the different transfer RNA molecules will also need to change to reflect these evolutionary changes, but the details of how this happens were not understood.
Now Yona et al. have explored this issue by studying yeast cells that lack a gene for one of the less common transfer RNA molecules (corresponding to the codon AGG, which specifies the amino acid arginine). At first this mutation resulted in slower growth of the yeast cells, but after being allowed to evolve over 200 generations, the rate of growth matched that of a normal strain with all transfer RNA genes. Yona et al. found that the gene for a more common transfer RNA molecule, corresponding to the codon AGA, which also specifies arginine, had mutated to AGG. As a result, the mutated yeast was eventually able to produce proteins as quickly as wild type yeast. Moreover, further experiments showed that the levels of some transfer RNAs are kept deliberately low in order to slow down the production of proteins so as to ensure that the proteins assume their correct structure.
But does the way these cells evolved in the lab resemble what happened in nature? To address this question Yona et al. examined a database of transfer RNA sequences from more than 500 species, and found evidence for the same codon-based switching mechanism in many species across the tree of life.