Molecular biologists time travel – over 3 billion years
A research group working at Uppsala University has successfully studied “translational factors” – important components of a cell’s protein synthesis machinery – that are billions of years old. By studying these old “resurrected” factors, the researchers were able to establish that they had much broader specificities than their current, more specialized counterparts.
In order to survive and thrive, all cells contain an internal protein synthesis factory. These are ribosomes and associated translational factors that work together to ensure that the complex process of protein production runs smoothly. While almost all of the components of modern translational machinery are well known, until now scientists were unsure how the process evolved.
The new study, published in the journal Molecular Biology and Evolution, took the research group led by Professor Suparna Sanyal from the Department of Cellular and Molecular Biology on an epic journey into the past. A previously published study used a special algorithm to predict DNA ancestor sequences of an important translational factor called thermo-unstable elongation factor, or EF-Tu, dating back billions of years. The Uppsala research group used these DNA sequences to resuscitate ancient bacterial EF-Tu proteins and then to study their properties.
The researchers examined several nodes in the evolutionary history of EF-Tu. The oldest proteins they created were around 3.3 billion years old.
“It was amazing to see that the ancestral EF-Tu proteins matched the geological temperatures on Earth at their corresponding periods. It was much hotter 3 billion years ago and these proteins worked well at 70 ° C, while proteins 300 million years old could only withstand 50 ° C, ”explains Suparna Sanyal.
The researchers were able to show that the ancient elongation factors are compatible with various types of ribosomes and can therefore be classified as “generalists”, while their modern descendants have evolved to perform “specialized” functions. While this makes them more efficient, they require specific ribosomes to function properly. The results also suggest that the ribosomes probably evolved their RNA core before the other associated translation factors.
“The fact that we now know how protein synthesis has evolved so far allows us to model the future. If the components of translation machines have already evolved to such a level of specialization, what will happen in the future, for example, in the case of new mutations? Suparna Sanyal wonders.
The fact that researchers have demonstrated that it is possible to recreate such ancient proteins, and that extremely ancient translation factors work well with many different types of ribosomes, indicates that the process is of potential interest for product research. protein pharmaceuticals. If it turns out that other ancient components of protein synthesis were also generalists, it might be possible to use these ancient variants to produce therapeutic proteins with unnatural or synthetic components in the future. .
Reference: “Kinetic analysis suggests the evolution of ribosome specificity in the modern elongation factor-Tus of“ generalist ”ancestors” by Arindam De Tarafder, Narayan Prasad Parajuli, Soneya Majumdar, Betül Kaçar and Suparna Sanyal, 19 April 2021, Molecular biology and evolution.
DOI: 10.1093 / molbev / msab114