The dual origin of the first living cells

The origin of life is often described as a sudden transition from chemistry to the first cell, as if, at a certain point, an organism had appeared that was already equipped with a membrane, a complete metabolism and everything it needed to live away from the place where it was born. A new study published in "Science Advances" proposes a different story, in which life is thought to have gone through a long phase of dependence on the mineral environment and only subsequently acquired, via two separate pathways, the ability to sustain itself as an autonomous cell. Bacteria and archaea would thus be descended from a common ancestor still tied to hydrothermal vents, but would have independently completed their emancipation from the geological environment, giving rise to two profoundly different cellular architectures.

The site proposed by the authors consists of alkaline hydrothermal vents fed by serpentinisation, a reaction between water and ocean floor rocks that produces hydrogen and creates metal-rich environments capable of facilitating chemical transformations. The mineral walls are criss-crossed by a network of tiny cavities in which substances can become concentrated, whilst the difference in acidity between the hot spring fluids and seawater provides a natural gradient that can be used as a source of energy. In this scenario, the chemistry necessary for life began before cells capable of producing it entirely existed: some reactions took place thanks to biological molecules and primitive proteins, whilst others were catalysed by iron, nickel, cobalt and other catalysts present in the rock.

That primordial form of life was not merely a mixture of organic substances. The last universal common ancestor of bacteria and archaea, known by the acronym LUCA, already possessed a genetic code, the ribosomes that read that code, and the system necessary for synthesising proteins. LUCA was not the first living entity to appear on Earth, but rather the most recent common ancestor from which all present-day cells are descended. According to the new reconstruction, its enzymatic metabolism was still incomplete: it could transmit genetic information and produce enzymes, whilst continuing to obtain from the environment some of the reactions and compounds essential to its existence.

To trace back to such a remote stage, the authors compared the enzymes present in 552 bacterial genomes and 401 archaeal genomes, examining both the sequences and the three-dimensional structure of the proteins. The structure preserves traces of kinship for longer than the sequence and therefore allows the recognition of homologies that billions of years of evolution have made difficult to identify. Starting with the approximately four hundred reactions by which modern cells produce amino acids, nucleotides and cofactors from simple substances, the researchers attributed 166 enzyme families to LUCA. A further 89 are thought to have emerged along the branch leading to the ancestor of modern bacteria, whilst 38 belong to the archaeal branch; for other families, the distribution is too fragmented to allow for a definitive assignment.

The part of metabolism dedicated to the production of nucleotides, on which DNA and RNA depend, appears to have been essentially complete in the common ancestor. The synthesis of amino acids, cofactors and numerous intermediates of carbon metabolism, on the other hand, still has significant gaps. The difference has an understandable significance: the informational function of nucleotides – and therefore of the genetic code – could not be delegated to rock, whilst many of the chemical reactions necessary to produce simpler molecules could still be catalysed by the metals present in the hydrothermal vent. For almost half of the reactions considered, the authors cite experiments in which the same step, a similar step or an entire metabolic sequence takes place in water without enzymes, in the presence of metals and under conditions compatible with a hydrothermal system.

The earliest form of metabolism would therefore have been distributed between the organism and the environment in which it lived. Hereditary molecules and proteins ensured biological continuity, whilst the environment provided reagents, catalysts and energy. The distinction between organism and environment, which today appears clear-cut, was then more blurred: removing that system from the mineral pores would have meant depriving it of an essential part of its biochemistry.

Autonomy is thought to have been achieved when organisms began to replace the functions of rock with components produced by their own metabolism. Cofactors – small molecules that help enzymes transfer electrons or chemical fragments – are thought to have acted as mobile and selective substitutes for solid metals. A mineral catalyst can promote many different reactions without any particular precision; an enzyme associated with its own cofactor, on the other hand, recognises specific substrates and allows natural selection to control the rate of individual steps. The metabolic network thus acquired the ability to produce internally even the tools necessary for its own functioning.

It is at this point that the history of life splits into two. Bacteria and archaea inherited the genetic code, the ribosome and a substantial part of their metabolism from LUCA, but each completed what was still missing independently. The study identifies five reactions for which the two kingdoms of microorganisms employ enzymes that lack a recognisable common structure. Since the chemical transformation is the same whilst the proteins carrying it out belong to different families, the simplest explanation is that bacteria and archaea independently devised two solutions to the same problem.

Independence from the original hydrothermal source also required autonomous energy production. A free cell must maintain a difference in ionic concentration between its interior and exterior and utilise the flow of ions to power ATP synthesis. In hydrothermal vents, the gradient was provided by the geology; outside the source, it had to be generated by the cell. According to the proposed reconstruction, the two lineages developed different mechanisms to link energetically favourable reactions to the pumping of ions across the membrane, thereby replacing the natural gradient with a biologically constructed one.

The membranes, too, took different paths. In bacteria, membranes are composed mainly of molecules similar to simple fats, whilst in archaea they are made up of different, more resistant molecules, arranged in a mirror-image pattern and with different bonds. The constituents, their chemical arrangement and the enzymes that produce them all differ. This separation, known as the ‘lipid divide’, is so profound that it has fuelled decades of debate over what type of membrane LUCA possessed. The authors’ model suggests that the earliest enclosing structures were very simple membranes, formed spontaneously from molecules present in the environment, and that it was only later that bacteria and archaea independently developed the enzymatic systems necessary to build their own modern membranes.

At the end of the process, two cellular forms capable of moving away from the source had emerged from the same biological matrix. They shared the language of the genetic code and the fundamental functioning of ribosomes, but differed in the composition of their membranes, in numerous enzymes and in the mechanisms used to manage energy. The genetic code and biological descent would therefore have had a single origin, whilst the independent cell, capable of living without the catalytic support of the rock, would have emerged twice.

This interpretation inevitably encounters the limitations imposed by the depth of time. Genes may be lost, replaced or transferred from one group to another, and many archaeal enzymes remain poorly characterised. The authors themselves acknowledge that greater knowledge of bacteria may make the innovations within their branch appear more numerous. Geochemical analogues have been demonstrated for only part of the network, whilst the other reactions will require as yet unknown catalysts or different explanations. The work therefore offers a coherent reconstruction supported by genomic comparisons and chemical experiments, not a direct record of events that took place almost four billion years ago.

However, the separation of bacteria and archaea does not mark the end of the story of cell evolution. Much later, an archaeon belonging to a lineage related to the present-day Asgard group entered into a stable relationship with a bacterium closely related to the Alphaproteobacteria. The bacterium became the progenitor of the mitochondrion, whilst the association between the two partners contributed to the emergence of the eukaryotic cell, from which animals, plants, fungi and numerous single-celled organisms are descended. The precise sequence of events remains a matter of debate, but the endosymbiotic origin of the mitochondrion and the host’s archaeal ancestry are supported by converging phylogenomic data.

Eukaryotes still bear the marks of that union. The systems governing the reading and transmission of genetic information show a strong archaeal ancestry, whilst the mitochondrion and numerous metabolic functions derive from a bacterial contribution. Recent studies indicate that the composition was even more complex, with genes originating from other bacteria acquired during a long period of interaction within microbial communities. Even the central metabolism of eukaryotes retains a chimeric structure, in which components from the archaeal host and the bacterial partner have been integrated and reorganised over the course of more than two billion years.

The eukaryotic cell can be regarded, in this sense, as a third solution. It does not represent a simple return to the state prior to the separation, because bacteria and archaea had by then accumulated their own innovations and deep-seated incompatibilities. Symbiosis brought together elements of both genetic heritages within a new organisation, in which the descendant of the bacterium continued to produce energy as a mitochondrion, whilst the archaeal heritage provided much of the host cell’s information system and structure.

The narrative suggested by this new research therefore begins with a form of life that could not have existed without its hydrothermal vent. From that shared dependence, two distinct ways of forming a free-living cell emerged, remaining separate for long enough to become the two major primary branches of evolution. When some of their descendants eventually came together again, their integration gave rise to eukaryotic complexity. The geological environment had initially accomplished what life was not yet capable of; subsequently, bacteria and archaea ‘learnt’ separately to take over this role, whilst the eukaryotic cell – our cell – arose from the ability to combine, within a single system, the achievements gained along both paths.