Life has always been a mystery that fascinates us till death. Some of the most common questions about life have been ‘What is life?’ ‘What caused cells to merge?’ ‘What did the first protein look like?’ We know that the first protein appeared somewhere around 3.7 billion years ago, given the foundation of life, which was conducive for life.
Prof. Dan Tawfik of the Weizmann Institute of Science and Prof. Norman Metanis of the Hebrew University of Jerusalem have reconstructed protein sequences that may well resemble those ancestors of modern proteins, and their research suggests a way that these primitive proteins could have progressed to forming living cells. Their findings were published in the Proceedings of the National Academy of Sciences (PNAS).
The proteins, which encoded and remain in the genetic material are what binds the cell together. Scientists claim that the first proteins appeared way before cells. Proteins of today are compiled of 20 different amino acids, all of them essential to protein-building, and all arranged in the form of a polymer — a long, chain-like molecule — in which the placement of each amino acid is crucial to the protein’s function. However, there is a confusion about the first proteins arose. As we know, amino acids, which are the key ingredient in the ‘protein cake’ are produced by proteins themselves, which brings us to a chicken-and-egg kind of question, and it has only been partially answered until now.
The first proteins materialized from shorter protein segments called peptides. The peptides would have been sticky assemblies of the amino acids that were spontaneously created in the primeval chemical soup; the short peptides would have then bound to one another, over time producing a protein capable of some sort of action. In 1952, Miller and Urey experimented on the amino acid by replicating the conditions required for survival on Earth prior to life and included energy alternative, which could come from lightning or volcanoes. Showing amino acids could, under the right conditions, form without help from enzymes or any other mechanism in a living organism suggested that amino acids were the “egg” that preceded the enzyme “chicken.”
Tawfik, of the Institute’s Biomolecular Sciences Department, shares concerns on the theory, “but one vital type of amino acid has been missing from that experiment and every experiment that followed in its wake: amino acids like arginine and lysine that carry a positive electric charge.” These amino acids are significant to proteins, as they interact with DNA and RNA, both of which carry net negative charges.
RNA is the original molecule that carries information and makes copies of itself, hence any form of contact with positively charged amino acids would be necessary for the development for cells to thrive.
One positively-charged amino acid was noticed in the Miller-Urey experiments, an amino acid called ornithine that is today found as an intermediate step in arginine production, but is not, itself, used to build proteins. This baffled the research team who inquired “What if ornithine was the missing amino acid in those ancestral proteins?” They designed an original experiment to test this hypothesis.
The scientists began with a relatively simple protein from a family that binds to DNA and RNA, applying phylogenetic methods to infer the sequence of the ancestral protein. This protein would have been rich in positive charges — 14 of the 64 amino acids being either arginine or lysine. Next, they created synthetic proteins in which ornithine replaced these as the positive charge carrier.
The ornithine-based proteins weakly bound to DNA. In Metanis’ lab, however, the researchers found that simple chemical reactions could convert ornithine to arginine. Those chemical reactions occurred under those conditions assumed to have prevailed on Earth at the time the first proteins would have appeared. As more and more of the ornithine was converted to arginine, the proteins came more and more to resemble modern proteins, and to bind to DNA in a way that was stronger and more selective.
The scientists also discovered that in the presence of RNA, that the ancient form of the peptide engaged in phase separation (like oil drops in water) — a step that can then lead to self-assembly and “departmentalization.” And this, says Tawfik, suggests that such proteins, together with RNA, could form proto-cells, from which true living cells might have evolved.
Prof. Dan Tawfik is the incumbent of the Nella and Leon Benoziyo Professorial Chair.
Source: Weizmann Institute of Science