Unraveling the Evolutionary Link to Eukaryotic Cells

Just a decade ago, scientists had no idea Asgard archaea even existed. That changed in 2015 when researchers analyzing deep-sea sediments uncovered gene fragments hinting at a previously unknown group of microbes.

Using computational tools, the team assembled these fragments like pieces of a puzzle to reconstruct an entire genome. That’s when they realized they were looking at a new group of archaea.

Archaea, like bacteria, are single-celled organisms—but genetically, the two domains differ in significant ways, particularly in their cell membranes and metabolic systems.

As research progressed, microbiologists were able to classify this new group as a distinct subgroup of archaea, now known as Asgard archaea. Their name, drawn from Norse mythology, reflects their discovery near Loki’s Castle—a hydrothermal vent field along the Mid-Atlantic Ridge between Norway and Svalbard.

The timing of this discovery turned out to be ideal. Asgard archaea emerged as a key piece in the puzzle of how complex life evolved, acting as a potential link between simple archaea and eukaryotes—organisms like plants and animals whose cells contain a nucleus.

A Two-Branch Tree of Life?

Mounting evidence now suggests that eukaryotes may have evolved from Asgard archaea. If that’s the case, the traditional model of three life domains—bacteria, archaea, and eukaryotes—may need to be revised. Some researchers argue that eukaryotes should instead be considered a branch within Asgard archaea, effectively reducing the tree of life to two primary domains: bacteria and archaea (including eukaryotes).

At ETH Zurich, Professor Martin Pilhofer and his team have been exploring this idea by studying Asgard archaea in depth.

In a study published two years ago in Nature, the ETH group examined the cellular structure of Lokiarchaeum ossiferum, a member of the Asgard group. This archaeon was isolated from brackish sediment in a Slovenian water channel by Christa Schleper’s lab at the University of Vienna.

Pilhofer and postdoctoral researchers Jingwei Xu and Florian Wollweber found that Lokiarchaeum ossiferum contains actin-like proteins—structures long associated with eukaryotic cells.

“We found an actin protein in that species that appears very similar to the protein found in eukaryotes and occurs in almost all Asgard archaea discovered to date.”

— Martin Pilhofer, Professor, ETH Zurich

Using advanced microscopy techniques, the researchers showed that this protein—dubbed Lokiactin—forms filamentous structures, particularly within the microbes’ many tentacle-like projections.

“They appear to form the skeleton for the complex cell architecture of Asgard archaea,”

— Florian Wollweber

In eukaryotic cells, the cytoskeleton is made up of both actin filaments and microtubules. While actin provides structure and shape, microtubules—made from tubulin proteins—play a vital role in transporting materials and dividing chromosomes.

Until recently, the origins of these microtubules were unclear. In a newly published Cell study, the ETH team identified similar structures in Asgard archaea. Their experiments revealed that Asgard tubulins can form microtubules that resemble those found in eukaryotes, though they are somewhat smaller.

Interestingly, only a small number of Lokiarchaeum cells produce these microtubules. Tubulin genes appear to be limited to a few species within the Asgard group, unlike the more widespread actin genes.

The function of these tubulins—and the reason for their rarity—remains a mystery. In eukaryotes, microtubules support internal transport, often with the help of motor proteins that move cargo along the tubes. So far, the ETH team hasn’t observed any motor proteins in Asgard archaea.

“We have shown, however, that the tubes formed from these tubulins grow at one end. We therefore suspect that they perform similar transport functions as the microtubules in eukaryotes.”

— Jingwei Xu, Study Co-First Author, ETH Zurich

Xu produced the tubulins using insect cell cultures and analyzed their structure in detail.

The research was a collaborative effort involving experts in microbiology, biochemistry, cell biology, and structural biology.

“We would never have progressed so far without this interdisciplinary approach,”

— Martin Pilhofer

A Glimpse into Early Eukaryotic Evolution

Could the cytoskeleton have been a prerequisite for the rise of complex life? While some questions remain open, the researchers are increasingly convinced that it played a key role in the evolution of eukaryotic cells.

One hypothesis is that an Asgard archaeon used its cellular extensions to capture a bacterium. Over time, that bacterium evolved into a mitochondrion—the energy powerhouse found in modern eukaryotic cells. The nucleus and other compartments followed, paving the way for the eukaryotic lineage.

“This remarkable cytoskeleton was probably at the beginning of this development. It could have enabled Asgard archaea to form appendages, thereby allowing them to interact with, and then seize and engulf a bacterium.”

— Martin Pilhofer

What’s Next for Asgard Archaea Research?

Pilhofer’s team is now shifting focus to explore the functions of actin filaments and archaeal tubulin, as well as the resulting microtubule structures. They’re also aiming to identify surface proteins found on Asgard cells. The hope is to develop custom antibodies that will help researchers isolate these microbes from complex microbial communities.

“We still have a lot of unanswered questions about Asgard archaea, especially regarding their relation to eukaryotes and their unusual cell biology. Tracking down the secrets of these microbes is fascinating,”

— Martin Pilhofer