Uppsala University: Molecular Biologists Travel Back in Time Over 3 Billion Years

A team of scientists from Uppsala University has succeeded in studying ‘translation factors’ – basic elements of a cell’s protein synthesis process – that are billions of years old. By examining these ancient ‘resurrected’ factors, the scientists were able to prove that they had much deeper specificities than their present-day, more functional counterparts.

To sustain and evolve, all cells carry an in-house protein synthesis factory. This consists of ribosomes and related translation factors that work mutually to ensure that the complex protein production process works smoothly. While nearly all elements of the modern translational process are well known, until now researchers did not know how the process evolved.

Uppsala University: Molecular Biologists Travel Back in Time
The EF-Tu cycle in protein synthesis. Source: Molecular Biology and Evolution

The new research, issued in the publication Molecular Biology and Evolution, took the study team guided by Professor Suparna Sanyal of the Department of Cell and Molecular Biology on an epic journey back into the past. Earlier issued research used a unique algorithm to evaluate the DNA sequences of ancestors of an essential translation factor known as EF-Tu, or elongation factor thermo-unstable, going back billions of years. The study team at Uppsala university utilized these DNA sequences to regenerate the antiquated bacterial EF-Tu proteins and then to examine their attributes.

The scientists examined many nodes in the evolutionary history of EF-Tu. The oldest proteins they produced were around 3.3 billion years old.

“It was astonishing to witness that the ancestral EF-Tu proteins tone with the geological temperatures prevailing on Earth in their similar time periods. It was extremely warmer 3 billion years ago and those proteins performed fine at 70°C, while 300 million-year-old proteins were only capable to withstand 50°C,” says Suparna Sanyal.

The scientists were able to show that the ancient elongation factors are cooperative with numerous kinds of the ribosome and therefore can be categorized as ‘generalists’, whereas their present-day descendants have emerged to fulfill ‘specialist’ functions. While this makes them more effective, they need particular ribosomes to work properly. The outcomes also recommend that ribosomes probably evolved their RNA core before the other connected translation factors.

“The truth is that we now understand how protein synthesis developed up to this time period makes it feasible for us to shape the future. If the translation process elements have already emerged to such a level of specialization, what will happen in the future, for example, in the case of distinct modifications?” ponders Suparna Sanyal.

The fact that researchers have demonstrated that it is feasible to recreate such ancient proteins and that notably, old translation factors operate well with various types of the ribosome, indicates that the method is of potential importance for protein pharmaceuticals study. If it turns out that other ancient elements of protein synthesis were also generalists, it might be desirable to use these ancient alternatives to create therapeutic proteins in the future with non-natural or synthetic elements.

Journal Reference: 

“Kinetic Analysis Suggests Evolution of Ribosome Specificity in Modern Elongation Factor-Tus from ‘Generalist’ Ancestors” by Narayan Prasad Parajuli, Suparna Sanyal, Arindam De Tarafder, Soneya Majumdar, and Betül Kaçar, 19 April 2021, Molecular Biology and Evolution.

DOI: 10.1093/molbev/msab114

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