The origins of complex life: clues hidden within archaea

Nature reports on a rather unusual scientific competition: several research teams are attempting to cultivate some of the most difficult-to-grow microorganisms known to us – tiny cells recovered from marine sediments and other oxygen-poor environments, which can take days or weeks to divide and are often so dependent on the organisms living alongside them that they cannot grow on their own. They belong to the Asgard group, a group of archaea discovered only about ten years ago; Archaea are single-celled microorganisms without a nucleus; for a long time they were confused with bacteria but are now recognised as a profoundly distinct branch of life. The Asgards are of particular interest because they are the closest known relatives to the lineage from which the eukaryotic cell arose – that is, the type of cell of which we are made, and of which animals, plants, fungi and protists.

The stakes are therefore much higher than the discovery of some new microorganism, because the origin of life seeks to explain how, on the early Earth, chemical processes produced the first systems capable of reproducing and evolving; whilst alongside this there is a second question regarding origins, less well known to the general public but almost as important: how that life – which for an immense period of time consisted exclusively of relatively simple cells – managed to produce the complex cell from which almost everything we now call complex life is descended.

For around two billion years after the emergence of the first life forms, only organisms consisting of cells without a nucleus existed on Earth; bacteria and archaea achieved – and still maintain today – an extraordinary variety of forms and metabolic processes, dominating many of the planet’s environments, whilst their cellular organisation remains profoundly different from our own. At a certain point in Earth’s history, however, a larger cell appeared, equipped with a nucleus in which to store DNA, internal membranes capable of creating specialised compartments, and a network of filaments – the cytoskeleton – with which to change shape, organise its interior and move materials from one region to another; mitochondria also emerged—the structures that still today enable our cells to harness the energy contained in nutrients with great efficiency.

That was one of the greatest transitions in the history of life, because multicellularity would emerge much later and along different evolutionary lines, giving rise separately to animals, plants, fungi and other multicellular organisms; yet all these histories depend on the earlier emergence of the eukaryotic cell. Before an animal could be formed, it was in fact necessary to have cells capable of growing large, of finely controlling their own shape and contents, of moving molecules within them and of utilising energy efficiently; eukaryogenesis—that is, the process through which this new type of cell arose—therefore constitutes, in a very concrete sense, the origin of complex life.

One of the latest organisms that could help us reconstruct that transition is called Nerearchaeum marumarumayae and was recovered from the microbial communities associated with the stromatolites of Shark Bay in Western Australia; stromatolites are layered mineral structures built up by the activity of microorganisms and have become famous because similar forms have left some of the oldest traces of life on Earth. After years of work, the researchers have succeeded in obtaining a culture in which Nerearchaeum accounts for around 89 per cent of the cells, whilst the rest of the culture is dominated by a bacterium, Stromatodesulfovibrio nilemahensis, and it is precisely the relationship between the two that appears to be an essential part of the story.

Nerearchaeum produces certain small molecules that the bacterium can utilise, whilst the bacterium is capable of producing compounds on which the archaeon appears to depend; thus, the two organisms do not simply share the same environment, but intertwine part of their survival through each other’s metabolism. When the researchers observed them using cryo-electron tomography – a technique that allows frozen cells to be reconstructed in three dimensions almost instantaneously – they saw that the archaeon and bacterium may be connected by extremely thin tubular structures. This observation is significant because it reveals something that has long occupied a central position in reconstructing the origin of eukaryotes: the possibility that a very close metabolic relationship between an archaeon and a bacterium preceded their integration into a single cell.

The reason we are specifically looking for a pair consisting of an archaeon and a bacterium stems from one of the most spectacular discoveries in 20th-century biology: the mitochondria present in our cells are descended from bacteria which, in the very distant past, began to live permanently inside another cell and which, over the course of evolution, lost a huge part of their autonomy, transferred many of their genes into the host’s DNA and eventually became indispensable components of the new cell. This process is called endosymbiosis, because one organism comes to live inside another and, generation after generation, the relationship becomes so close that it gives rise to a new biological unit.

We still carry traces of this within every one of our cells, given that mitochondria retain a small amount of their own DNA, divide in a manner reminiscent of bacteria, and numerous components clearly reveal their bacterial origin; the event that produced them therefore did not represent the emergence out of nowhere of a new cellular structure, but the result of the evolutionary union between two organisms that, until that point, had followed separate evolutionary paths.

We know quite a lot about one of the two protagonists, because the future mitochondrion was derived from a bacterium belonging to a large lineage called Alphaproteobacteria, whilst the identity of the other protagonist has been much more difficult to piece together. We knew it was linked to archaea, because many of the fundamental systems by which eukaryotes copy DNA, produce RNA and build proteins have close relatives within that very group, but we were missing something that resembled our ancestor closely enough to allow us to imagine what sort of cell the future mitochondrion had encountered.

In 2015, the picture changed when, by analysing DNA recovered from seabed sediments, researchers reconstructed the genome of a previously unknown organism, named Lokiarchaeum; in the years that followed, other related groups emerged, to which names taken from Norse mythology were assigned, including Thor, Odin and Heimdall, and the entire group came to be known as Asgard.

Their position in the evolutionary tree immediately attracted attention, as eukaryotes were found to be closely related to these archaea, and a second surprise followed shortly afterwards, one that was even more significant from a biological point of view: their genomes contained genes for proteins similar to those that eukaryotes use to organise the cell, alter its shape and control its membranes, to such an extent that some of those proteins had, until then, been regarded almost as a hallmark of the eukaryotic cell.

The finding altered the problem, because it became possible to imagine that the cell from which we are descended was already more sophisticated than previously thought before encountering the bacterium destined to become the mitochondrion; yet an enormous limitation remained, given that for years the Asgard were known almost exclusively through their DNA, and attempting to reconstruct their behaviour was, to some extent, like trying to understand an organism by referring to its genetic manual without ever having seen it.

The next breakthrough came when certain research groups finally succeeded in cultivating them, and the first success was Prometheoarchaeum syntrophicum, achieved after more than ten years of attempts using marine sediments. It is a tiny cell, grows extremely slowly and is metabolically dependent on other microorganisms, whilst thin, branched membrane extensions protrude from its surface.

It is merely one of several possible models and many details remain open to debate, but the significance of Prometheoarchaeum lay elsewhere, because it demonstrated that an archaeon belonging precisely to the group closest to eukaryotes could indeed live in very close dependence on other microorganisms and produce large expansions of its own cell surface, thereby taking two characteristics required by certain scenarios of eukaryogenesis out of the realm of pure theoretical possibility.

Then came Lokiarchaeum ossiferum, and upon observing it in three dimensions, the researchers discovered that a network of filaments runs through the cell and its protrusions, formed by a protein related to actin – one of the main proteins in our cytoskeleton, which is essential for enabling eukaryotic cells to change shape, move and organise their internal structure. The discovery thus showed that at least some elements of the cellular machinery we typically consider to be eukaryotic already existed, in a simpler form, in our archaeal relatives.

Nerearchaeum now adds a further element, as it allows us to directly observe an Asgard linked to a bacterium through a metabolic relationship and close physical contact; taken together, these organisms are transforming a problem that, until a few years ago, was addressed almost exclusively through the comparison of genetic sequences. Researchers can now begin to see the cells, observe how they build their membranes, understand which partners they need, and verify what those proteins – which share an evolutionary history with our own – actually do.

Reconstructions of ancient genomes are also altering our understanding of the event, because all eukaryotes existing today are descended from a common ancestor that biologists call LECA, an acronym for Last Eukaryotic Common Ancestor, and LECA was not a rudimentary cell at the start of the transformation, but already possessed mitochondria and most of the fundamental components of a modern eukaryotic cell. When we encounter LECA in the evolutionary reconstruction, therefore, much of the revolution has already taken place and the real enigma lies in the preceding period, between the archaeal ancestor and LECA.

A recent study has sought to establish which of the two ancient partners provided the various cellular systems already present in the common ancestor of eukaryotes, and the picture that emerges is one in which many of the structures necessary for the organisation of the cell appear to have their roots in the Asgard lineage, whilst the contribution of the bacterial ancestor of the mitochondrion is particularly significant in systems related to energy production and management.

If this reconstruction continues to hold true, the origin of the eukaryotic cell will appear less and less as the encounter between a very simple archaeal cell and a bacterium capable of producing energy, and increasingly as the integration of two evolutionary histories that had already developed different capabilities: on the one hand, an archaeal cell that was acquiring the means to control its shape and membranes; on the other, a bacterium equipped with an energy metabolism destined to become the biochemical heart of the new cell.

It remains to be determined when and in what order the nucleus, the internal membrane systems, the more elaborate cytoskeleton and many of the other eukaryotic characteristics appeared; it also remains to be understood to what extent the emergence of the future mitochondrion enabled subsequent innovations, providing the cell with a previously unattainable level of energy and the means to manage it. There are still differing models on these points, and it is the Asgards who are, for the first time, providing experimental data with which to test them.

The significance of this issue lies in the scale of the event, because the origin of life seeks to explain how something capable of evolving first appeared on Earth, whilst the origin of the eukaryotic cell seeks to explain how, much later, that life acquired a new organisational structure that would make possible almost all the biological complexity visible around us.

For billions of years, the Earth was a planet of microbes and then, on a single occasion as far as we can reconstruct, two profoundly different cellular lineages eventually merged to produce a completely new type of organism; all the cells in our bodies, those of a sequoia, those of a fungus and those of a whale are descended from that innovation. Understanding how this happened therefore means reconstructing one of the very few stages in natural history without which the living world as we know it would never have existed.

And this is what makes the tiny, extremely slow archaea discussed in today’s issue of Nature so important: they do not carry the answer already encoded within them, nor do they represent ancestors frozen in time; rather, they allow us, for the first time, to observe at close quarters cells belonging to the branch of life closest to our own as they build complex structures, depend on other microorganisms and establish such close relationships with bacteria that we can glimpse, in their biological potential, some of the steps through which simple life was able to evolve into complex life.