A team of researchers led by Anton A. Komar, Ph.D., of Cleveland State University has uncovered fresh evidence of how genetic code governs protein production and folding in the cell.
In new findings published in the prestigious scientific journal Molecular Cell, Dr. Komar and his colleagues documented the impact of “synonymous codons” on protein quality. The genetic code is degenerate, i.e. most amino acids are encoded by more than one codon. These so-called synonymous codons were largely presumed to have the same meaning and were considered “silent,” since their substitutions did not change the amino acid sequence of the encoded proteins.
Dr. Komar’s research team highlighted the mechanism by which synonymous codons do affect protein folding, and therefore the actual function of the protein. Their work promises to deepen our understanding of how genetic diseases linked to silent mutations develop, which would allow physicians to create more specific, personalized treatments based on an individual’s genetic information and develop safer protein therapeutics.
“For nearly four decades, biomedical science has been driven in part by the Neutral Theory of Molecular Evolution, which in particular suggests that synonymous codons will be largely unaffected by selective evolutionary pressure and that synonymous mutations will be inconsequential to protein quality,” said Dr. Komar, director of CSU’s Center for Gene Regulation in Health and Disease. “Our results have specifically disproven this suggestion and illuminated the details of how protein quality is guided by synonymous codon usage.”
The team also included researchers from the Max Planck Institute for Biophysical Chemistry in Göttingen and Johann Wolfgang Goethe University in Frankfurt am Main, both in Germany. Their work was funded by the Human Frontier Science Program.