Changes in proteins as evolutionary mechanism

Evolution in yeast species (grey and red) with mass spectrometry in green (Image courtesy Villen Lab/University of Washington)
Evolution in yeast species (grey and red) with mass spectrometry in green (Image courtesy Villen Lab/University of Washington)

An article published in the journal “Science” describes a research that states the importance of the mechanism called post-translational modification (PTM) in evolution. An international team led by Pedro Beltrao of the European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI) and by Professor Judit Villen of the University of Washington investigated in particular phosphorylation obtaining information also useful in medical research such as that on cancer.

The research on evolution mechanisms focused on gene expression, which control among other things the production of proteins. However, cellular mechanism of post-translational modification plays an important role. In previous studies, the comparison of proteins in related species showed very few mutations so that kind of mechanism wasn’t considered important but in this new research it was discovered that a few mutations are needed to have a strong impact on the way in which proteins and cells work.

The researchers reconstructed the evolutionary history of phosphorylation sites, the modifications that can control proteins, in 18 species of unicellular fungi, specifically yeast, tracing their mutations. Until recently it wasn’t possible to study phosphorylation so thoroughly or for so many samples but technological advances with the applications to genetics such as bioinformatics and mass spectrometry now allows to conduct such research.

The analysis of phosphorylation sites indicates that most of them came about in relatively recent times in the evolution of the yeast species. This indicates that they are part of what makes the species different and an important factor in evolutionary diversity. The changes in phosphorylation are important in the adaptation of a species to a new situation as much as changes in gene expression.

These discoveries may also be useful in cancer research. Some anti-cancer drugs block tumors by blocking the proteins functioning mechanisms which allow their growth. The problem is that cancer mutations generate other post translational modifications circumventing the blocks created by the drugs. Most mutations are useless but the one that turns out to be useful is selected.

This research is connected to a series of works carried out over the years, some of which involved Pedro Beltrao. The study of yeasts allowed a better understanding of evolutionary mechanisms that are valid in general with perspectives that will be assessed over time in various fields.

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