Ostrava biologists helped to reveal an important moment in the evolution of cells

The collaboration of Ostrava biologists with colleagues in France and Canada has significantly advanced the understanding of how the eukaryotic cell and its complex molecular apparatus arose in evolution. Their research brings the important finding that the differences in the functioning of prokaryotic and eukaryotic cells are smaller than previously thought.  

The Ostrava scientists have published a scientific paper with the results of their work in the prestigious journal Nature Microbiology. Its first author is a young scientist from Prof. Marek Eliáš' team, Dr. Romana Vargová and it could materialize also thanks to to the support by the project LERCO

Cells, the basic building and functional units of all life, are essentially of two types. The well-known bacteria and the more enigmatic microorganisms referred to as Archaea are represented by the generally simpler prokaryotic cells. In contrast, animals and plants (and also fungi, algae, and protozoa) have cells with a much more complex organization and are referred to as "eukaryotic" (the name refers to the presence of a cell nucleus). There is no doubt that all eukaryotic cells are of a single origin and have arisen from prokaryotic ancestors. But exactly how this happened is one of the major, only partially answered, questions of biology. One sub-problem is to explain the origin of the large number of proteins (proteins) unique to eukaryotic cells.

The research group of Marek Eliáš at the Department of Biology and Ecology, Faculty of Science, OU has long been investigating a large group of proteins that underlie the complex and dynamically changing internal structure of eukaryotic cells. They are technically called "Ras superfamily GTPases". These proteins act as powerful regulators of a wide variety of molecular events in the cell, and their function depends on their ability to "switch" between two forms. The importance of the proteins of this superfamily is illustrated by the fact that mutations in its first discovered representative, the Ras protein itself, are one of the factors underlying the development of many human cancers.

Comparison of Ras superfamily proteins in different eukaryotic organisms shows that the common ancestor of all eukaryotes - an organism existing some 1.5 billion years ago - already possessed a rich repertoire of these proteins (see also earlier publications by R. Vargová and M. Eliáš: A Eukaryote-Wide Perspective on the Diversity and Evolution of the ARF GTPase Protein Family).

But where did these proteins come from? Key to answering this question was the decade-old discovery of a new subgroup of Archaea called "Asgard" (or Asgardarchaeota; see Figure 1), in which Dutch microbiologist Thijs Ettema and his collaborators played a central role. They, and subsequently other researchers, have characterised these microorganisms in detail and shown that they exhibit many features previously known only from eukaryotes. The Asgard group thus appears to be the evolutionary cradle of the eukaryotic cell.

Fig. 1: The first characterized representative of the archaeal group Asgard, technically called Candidatus Prometheoarchaeum syntrophicum. Source: Wikipedia (license CC BY-SA 4.0)

The emerging picture of this evolutionary connection has now been significantly complemented by a study carried out within the "Molecular Biology and Genomics " research programme of the LERCO project. The study was carried out by the team of M. Eliáš and colleagues in France and Canada and focused on the Ras superfamily proteins, or more precisely on a subset of them called the "Arf family". The paper in question is entitled "The Asgard archaeal origins of Arf family GTPases involved in eukaryotic organelle dynamics" and its central message is that the entire large eukaryotic Arf family has its evolutionary roots among proteins found in asgardarchaeotes. What's more, these prokaryotic ancestors of eukaryotes even "invented" a specific molecular mechanism that is typical of Arf family proteins and was previously thought to be exclusively eukaryotic. In fact, it has been shown that at least some of the newly recognized asgardarchaeal members of the Arf family - like their long-established eukaryotic relatives - change their structure during their functional cycle in such a way that the terminal part of the protein is "flipped", through which the whole protein then attaches to the cell membrane (see Figure 2).

Although it remains unknown for now what the Arf family proteins do in asgardarchaeal cells, the findings of our biologists and their international collaborators provide further important evidence that the differences in the functioning of prokaryotic and eukaryotic cells are smaller than previously thought. 

Fig. 2: Schematic representation of the functional cycle of Arf family proteins. The protein switches between two states, inactive (top) with the end part retracted (orange helix) and active (bottom) where the end part is flipped out and mediates the association of the protein with the cell membrane. Adapted from Yorimitsu et al, Frontiers in Plant Sciences 2014 (https://doi.org/10.3389/fpls.2014.004110). CC BY license

Marek Eliáš adds: "Our latest study is a beautiful example of scientific collaboration across disciplines and continents. The whole story started more than fifteen years ago. While carrying out computer analyses of genome sequences, I noticed genes indicating the existence of Arf family proteins in prokaryotes. However, the correct interpretation of these initial observations was only possible after Thijs Ettema and colleagues showed the existence of previously unknown asgardarchaeotes. This was followed by a massive flood of new genomic data, which we had to learn to navigate through and gradually process in order to properly map the occurrence of the Arf family proteins. This required a huge effort and these analyses were literally "unpacked" by my postdoc Romana Vargova (Figure 3), while on parental leave! She is the well-deserved first author of the whole article. However, it would never have been written if it had not been for my long-time collaborator Joel Dacks from the University of Alberta in Edmonton, Canada, who recruited two new colleagues, Julie Ménétrey from Université Paris-Saclay and Catherine Jackson from Université Paris Cité. Julie and her team took care of the detailed characterization of model representatives of the asgardarchaeal Arf family using good old X-ray crystallography, and the lab led by Cathy supplied key cell biology experiments. We are very happy with the outcome of our joint efforts and hope that our collaboration will bear more tasty fruits in the future."

Obr. 3: Romana Vargová, postdoktorandka ve skupině M. Eliáše a první autorka článku.