From Microbes to Complex Cells: Tracing the Origins of Life

An artist’s depiction of an Asgard archaeon, based on cryo-electron tomography data: the cell body and appendages feature thread-like skeletal structures, similar to those found in complex cells with nuclei. (Graphic: Margot Riggi, Max Planck Institute of Biochemistry)

A decade ago, the existence of Asgard archaea was completely unknown. But in 2015, scientists analyzing deep-sea sediments uncovered gene fragments pointing to an entirely new type of microbe.

Using computer modeling, researchers pieced together these genetic fragments like a puzzle, eventually reconstructing a complete genome. It was only then they realized they had discovered a previously unidentified group of archaea.

Although archaea, like bacteria, are single-celled organisms, they differ significantly in terms of genetics—particularly in their cell structure and metabolic functions.

Further investigation led microbiologists to locate and characterize the actual organisms, ultimately classifying them as a distinct subgroup of archaea known as Asgard archaea. Their name, inspired by Norse mythology’s heavenly realm, was chosen due to their initial discovery near Loki’s Castle, a hydrothermal vent located along the mid-Atlantic Ridge between Norway and Svalbard.

Asgard archaea quickly became a breakthrough in scientific research—they emerged as a potential missing link between archaea and eukaryotes, the domain of life that includes organisms with nucleus-containing cells, such as plants and animals.

Tree of life with one branch fewer

In recent years, increasing evidence has pointed to a close relationship between Asgard archaea and eukaryotes, suggesting that eukaryotes may have actually evolved from this group. This unexpected finding challenges the traditional classification of life into three domains: bacteria, archaea, and eukaryotes.

As a result, some scientists have proposed reclassifying eukaryotes as a subgroup within the Asgard archaea. This shift would effectively reduce the number of life’s domains from three to two: bacteria and archaea, with eukaryotes falling under the archaeal umbrella.

Redrawing the tree of life, with eukaryotes descending from Asgard archaea.  (Graphic: Florian Wollweber / ETH Zurich)

At ETH Zurich, Professor Martin Pilhofer and his team have been captivated by Asgard archaea and have spent several years studying these enigmatic microbes.

In a paper published in Nature two years ago, the ETH researchers delved into the cellular structure and organization of Lokiarchaeum ossiferum. This particular Asgard archaeon, originally found in sediment from a brackish water channel in Slovenia, was isolated by Christa Schleper’s lab at the University of Vienna.

Pilhofer and his postdoctoral colleagues, Jingwei Xu and Florian Wollweber, discovered that Lokiarchaeum ossiferum contains certain structural features also seen in eukaryotic cells. “We identified an actin protein in this species that closely resembles the version found in eukaryotes – and it appears to be common among nearly all Asgard archaea identified so far,” says Pilhofer.

In their initial research, the team used a combination of advanced microscopy techniques to show that this protein, named Lokiactin, forms filament-like structures, particularly within the microbes’ many tentacle-like extensions. “These filaments likely act as a cellular skeleton, helping to shape the complex architecture of Asgard archaea,” Wollweber explains.

Alongside actin filaments, eukaryotic cells also contain microtubules—hollow, tube-shaped structures that make up the second major element of the cytoskeleton. Made from tubulin proteins, microtubules play a crucial role in transporting materials within the cell and ensuring proper chromosome separation during cell division.

Until recently, the origin of microtubules remained a mystery. However, in a newly published study in Cell, researchers at ETH Zurich identified similar structures in Asgard archaea and detailed their composition. Their findings revealed that Asgard tubulins can form microtubule-like structures that closely resemble those in eukaryotes, though they are somewhat smaller in size.

Interestingly, only a small number of Lokiarchaeum cells were found to produce these microtubules. Moreover, unlike actin, tubulin proteins appear to be limited to just a few species within the Asgard archaea group.

Expansion microscopy, a novel light microscopy technique, shows the cytoskeleton of Asgard archaea: Actin filaments (green) and, in the right-hand image, a microtubule (violet)  (Image: from Wollweber F, et al. Cell, 2025)

Scientists are still unsure why tubulin proteins are so rare in Lokiarchaea or what specific role they play in these cells. In eukaryotes, microtubules are essential for internal transport, with motor proteins sometimes moving along them like tracks. So far, the ETH researchers have not found any evidence of such motor proteins in Asgard archaea.

“However, we did observe that these tubulin-based tubes grow from one end,” explains Jingwei Xu, co-first author of the Cell study. “This suggests they may serve a similar transport role to microtubules in eukaryotic cells.” Xu produced the tubulin proteins using insect cell cultures and analyzed their structure.

The study was the result of close collaboration between experts in microbiology, biochemistry, cell biology, and structural biology. “We would never have made this much progress without such an interdisciplinary effort,” says Pilhofer, proudly.

The structure of an Asgard microtubule, which consists of just five filaments (compared to 13 in eukaryotes).  (Image: from Wollweber F, et al. Cell, 2025)

Was the cytoskeleton crucial to the emergence of complex life? While some aspects are still unclear, researchers strongly believe it played a key role in the evolution of eukaryotic cells.

This pivotal moment may have taken place eons ago, when an Asgard archaeon used its extensions to interact with a bacterium. Eventually, that bacterium became a mitochondrion—the energy-producing organelle found in modern cells. As evolution continued, other cellular structures like the nucleus and additional compartments emerged, leading to the formation of the first eukaryotic cells.

“This remarkable cytoskeleton was likely a foundational element in that process,” says Pilhofer. “It may have enabled Asgard archaea to develop appendages, which allowed them to interact with and ultimately engulf a bacterium.”

Fishing for Asgard archaea

Pilhofer and his team now plan to focus on understanding the roles of actin filaments and archaeal tubulin, along with the microtubules they form.

Another key goal is to identify the proteins present on the surface of these microbes. Pilhofer hopes his team can develop custom-designed antibodies that target these proteins, allowing scientists to selectively isolate Asgard archaea from mixed microbial communities.

From Microbes to Complex Cells: Tracing the Origins of Life

“There’s still so much we don’t know about Asgard archaea—particularly their connection to eukaryotes and their unique cellular biology,” Pilhofer says. “Uncovering the mysteries of these microbes is truly captivating.”