The Norse god Loki holding a Lokiarchaeota profilin protein crystal standing in front of Lokiarchaeota profilin/rabbit actin crystals

Protein crystal images © 2018 A*STAR Institute of Molecular and Cell Biology; Image of Loki from manuscript SÁM 66 of the Árni Magnússon Institute for Icelandic Studies

Biology of our ancient ancestor takes shape

14 Jan 2019

Primitive microbes have cytoskeletal proteins that are structurally and functionally similar to those found in humans

The recent discovery of a new lineage of microbes has overturned biologists’ understanding of the evolution of complex life on Earth. Genomic studies of Asgard archaea revealed that they carry many genes previously thought to be found only in nucleus-bearing eukaryotes, suggesting they may be closely related to more complex life forms such as humans.

Study authors Robert Robinson (left) and Caner Akil (right).

© 2019 A*STAR Institute of Molecular and Cell Biology

Two A*STAR scientists have now strengthened the case for this evolutionary scenario by showing that these small creatures have a dynamic network of cytoskeletal proteins, a feature that gives cells shape, and was previously thought of as specific to eukaryotes.

What’s more, the A*STAR investigators found that one of these archaeal proteins, profilin, that serves to bind and regulate the dynamics of a cytoskeletal protein called actin — had the same function as its counterpart in eukaryotes. The primordial profilin could even bind actin derived from a mammal.

“After around two billion years of divergent evolution, it is staggering that these proteins are compatible,” says Robert Robinson, a research director at the A*STAR Institute of Molecular and Cell Biology, who led the study published in Nature.

Scientists in Sweden first identified Asgard archaea in 2015, from sediments taken deep below the Arctic Ocean, near a series of hydrothermal vents called Loki’s Castle. Those microbes became known as Lokiarchaeota, named after the Norse shape-shifting god, and every Asgard lineage found thereafter — as well as the word Asgard — has come from Norse mythology.

No Asgard archaea have yet been grown in the laboratory or observed under a microscope. So, Robinson and his graduate student Caner Akil took gene sequences encoding profilin proteins from a few Asgard lineages and inserted the DNA into an easily cultured bacterium. They then purified the profilins made by the bacterium and worked out the protein structures using X-ray crystallography.

Although these proteins shared little sequence similarity at the amino acid level with their eukaryotic counterparts, the researchers discovered that the overall shape of Asgard and human profilins were topologically alike — a sign of evolutionary links.

Robinson and Akil were not able to produce functional Asgard actin, profilin’s binding partner, in their bacterial expression system. As an alternative, they used rabbit actin and tested whether Asgard profilin could bind to the actin and modulate its kinetics.

Indeed, the Asgard protein tethered and regulated the mammalian actin only slightly less efficiently than profilin from humans. Considered together, these results indicate that Asgard archaea, unlike other organisms lacking a nucleus, harbor a primitive, but dynamic cytoskeleton, and thus probably shared a common ancestor with eukaryotes some two billion years ago.

“We are now comparing other eukaryotic-like Asgard proteins to the human counterparts,” Robinson says. “We hope to understand how the eukaryotic protein machineries became more sophisticated over time.”

The A*STAR-affiliated researchers contributing to this research are from the Institute of Molecular and Cell Biology.  For more information about the team’s research, please visit the Structural Bases of Pathogenicity and Disease Laboratory webpage.

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Akil, C. & Robinson, R. C. Genomes of Asgard archaea encode profilins that regulate actin. Nature 562, 439–443 (2018). | article

About the Researcher

Bob (Robert) Robinson

Research Director

Institute of Molecular and Cell Biology
Bob obtained a BSc (1987) in Chemistry from King's College, London University, an MSc (1990) in Biochemistry from the University of British Columbia, and a DPhil (1996) in Structural Biology from Oxford University. During his postdoctoral studies at the Salk Institute for Biological Studies (1996-2001), Bob solved the X-ray structure of Arp2/3, an actin-nucleating complex consisting of seven proteins. In 2001, Bob was appointed as a Senior Lecturer at Uppsala University. There, the research group elucidated structures of key actin-regulating proteins. Bob became an EMBO Young Investigator in 2003. Bob joined the A*STAR Institute of Molecular and Cell Biology (IMCB) as a Principal Investigator in 2005 and became a Research Director in 2011. He holds an adjunct position at the Department of Biochemistry at the National University of Singapore, and serves on the Editorial Boards of Open Biology and Cytoskeleton. In Singapore, the laboratory has been instrumental in deciphering the evolutionary and structural bases of how force generated from polymerizing motors is integrated into biological processes. He has also recently accepted a full professorship at the Research Institute for Interdisciplinary Science at Okayama University in Japan.

This article was made for A*STAR Research by Nature Research Custom Media, part of Springer Nature