An international team, including DoM's Dacks Lab, trace the origins of cellular complexity

Dr. Joel Dacks's team, along with teams from three other countries, dive deep into one of biology's greatest mysteries: the internal compartments and protein machinery of eukaryotes, which resulted in a transformative evolutionary leap for life on Earth.

28 January 2025

Trees, lobsters, yeast, malaria, and you share one thing in common—you are all eukaryotes. Eukaryotic cells are characterized by internal compartments and are relatively large compared to their bacterial and archaeal ancestors. This evolutionary leap, which occurred about a billion and a half years ago, fundamentally transformed life on Earth. Understanding how this transition happened remains one of the biggest questions in evolutionary biology today.

The Puzzle of Cellular Compartments

One elusive milestone in this evolutionary journey is the development of cellular compartments and protein machinery that move material within our cells. A key example is the Arf family of enzymes, a diverse group of proteins that regulate compartment dynamics and material transport. These proteins, shared by all eukaryotes, are essential to normal cellular function, and mutations in Arfs can lead to diseases such as cancer and vision defects. But where did the Arf family originate, and when did it arise?

A Landmark Discovery

A landmark paper, by Vargová et al., published in Nature Microbiology, sheds new light on this specific milestone and the broader question of cellular compartments. This study was a collaboration between the teams of Dr. Catherine Jackson (U of A alumna ’84) at the Institut Jacques Monod in Paris, France, Prof. Joel Dacks in the Department of Medicine at the University of Alberta in Edmonton, Canada, Prof. Marek Eliáš at the University of Ostrava in Ostrava, Czech Republic, and Dr. Julie Ménétrey at Université Paris-Saclay in Gif-sur-Yvette, France.

ArfR Proteins: Tracing the Origins

The research describes a newly identified group of proteins in archaeal microbes—ArfR proteins—thought to be the closest relatives of eukaryotes. These proteins not only serve as the evolutionary precursors to eukaryotic Arfs, but they also share the unique biochemical mechanism of how Arf family proteins localize in cells. This is a "smoking gun" clue about where and when the Arf family of cellular machinery emerged and will change the conversation about the series of events that gave rise to our ancient eukaryotic ancestors, and eventually, nearly all complex life that you see on Earth today.

 Structural comparison of the GDP-bound form of asgardarchaeote and eukaryotic Arf family proteins.

{Vargová R, Chevreau R, Alves M, Courbin C, Terry K, Legrand P, Eliáš M, Ménétrey J, Dacks JB, Jackson CL. The Asgard archaeal origins of Arf family GTPases involved in eukaryotic organelle dynamics. Nature Microbiology. 2025 Jan 23:1-4.}


Dr. Joel Dacks

Dr. Joel Dacks is a Professor in the Division of Infectious Diseases of the Department of Medicine at the University of Alberta.

The long-term goal of his research program is to understand the evolution and diversity of the eukaryotic membrane-trafficking system.