Swiss team learns how mistranslation can affect evolutionary fitness, lessen predictability

Sometimes increased evolutionary fitness can be achieved when mistakes are made in the commonly assumed mutational pathways of adaptive DNA mutation. How this occurs is important in understanding what influences evolution and how predictable evolution is. 

A June 18 article in the Journal of Evolutionary Biology by a team of researchers at the University of Zurich in Switzerland, studied how mistranslation by messenger RNA (mRNA) occurs and influences the predictability of evolution. Mistranslation, as defined by the authors, means "the erroneous incorporation of amino acids into nascent proteins" in an organism.

The research team, from the university's Department of Evolutionary Biology and Environmental Studies, looked at how different degrees of mistranslation helped or hindered an organism's use of normally less accessible alternative evolutionary pathways to reach a state of high fitness. 

The researchers studied the growth of beta-lactamase TEM-1, a substance that determines antibiotic resistance, in the bacterium Escherichia coli when the antibiotic cefotaxime was introduced. They reconstructed the DNA mutations involved with resistance to cefotaxime and compared the effect of low mistranslation rates to high mistranslation rates on the TEM-1.

The research team notes that mistranslation causing amino acid variations is up to about 10⁵ times more frequent than DNA mutations. 

In their reconstruction of adaptive DNA mutations, they found "that some of the DNA mutations do not change fitness under low mistranslation but cause a significant increase in fitness under high-mistranslation." Thus, the high mistranslation rates made it more likely that the accessibility of high cefotaxime-resistant genotypes can evolve.

The researchers describe two ways that elevated mistranslation "increases the diversity of evolutionary trajectories toward high cefotaxime-resistance genotypes." First, it increases the benefit of adaptive DNA mutations. Second, the DNA mutations "form an epistatic network that can lead to mutually exclusive evolutionary trajectories toward different high cefotaxime-resistance genotypes."

(Epistasis refers to the dependence of a gene mutation's effect on mutations in other genes.)

The result is that the evolutionary trajectories of the organism become unpredictable.

The researchers conclude that "The life of a cell is intrinsically noisy, and this stochasticity [randomness] might have substantial impact on the trajectories of adaptive evolution."