Russell and coworkers proposed that networks of microcompartments that exist at both extant and ancient hydrothermal vents, and consist, primarily, of iron sulfide could be ideal habitats for early life. These inorganic compartment networks provide gradients of temperature and pH that could fuel primordial energetics, and versatile catalytic surfaces for primitive biochemistry 55, 56
. These might have been the sites of prebiological and pre-cellular biological evolution, from mixtures of organic molecules to the putative, primordial RNA world to the independent escapes of archaeal and bacterial cells 23, 45
. These compartments are envisaged being inhabited by diverse populations of genetic elements, initially, segments of RNA, subsequently, larger and more complex RNA molecules encompassing one or a few protein-coding genes, and later yet, also DNA segments of gradually increasing size (). Notably, a computer simulation study has shown that, in the presence of thermal gradient that inevitably exists at a hydrothermal vent, extremely high concentrations of small molecules and polymers can be reached 57
, a condition that would substantially facilitate a variety of reactions including RNA ligation 58
The primordial virus world model of pre-cellular evolution
Thus, early life forms, likely including LUCA, are perceived as complex ensembles of genetic elements that inhabited networks of inorganic compartments 45, 59
. A key feature of this model is that genetic elements with different replication and expression strategies (including replicating DNA segments) encoding distinct replication machineries would coexist within a network or even within the same compartment. Thus, the earlier, somewhat artificial scheme, in which the universally conserved components of the DNA replication machinery were implicated in a primordial, retrovirus-like replication cycle 22
, might be superfluous. The model of the compartmentalized primordial gene pool implies evolution of the retrovirus-like replication cycle within the RNA-protein world and subsequent evolution of diverse DNA replication systems () but does not necessarily require the components of these distinct genetic systems to function together within the same replication cycle.
This model explains the lack of homology between the membranes, membrane biogenesis systems, and the DNA replication machineries of archaea and bacteria by inferring a LUCA that did not have a single, large DNA genome and was not a membrane-bounded cell. However, under this model, the primordial, pre-cellular life forms are envisaged as “laboratories” in which various strategies of genome replication-expression as well as rudimentary forms of biogenic compartmentalization were “invented” and tried out ( and see below).
The central point of this scenario of life’s early evolution is the virus-like nature of the perceived pre-cellular life forms. The idea that viruses could be related to the first life forms is almost as old as virology itself. Apparently, it was first proposed by Felix d’Herelle, the discoverer of bacteriophages 60
and was incorporated and developed by J. B. S. Haldane in his classic 1928 essay on the origin of life 61
. Haldane came up with the striking speculation that the first self-reproducing agents were viruses or virus-like agents and that a virus stage in life’s evolution preceded the emergence of cells. Subsequently, the concept of the primordial origin of viruses was, largely, abandoned as it became obvious that viruses were obligate intracellular parasites that depend on the host cells for most of their functions; instead, the scenarios of cell degeneration or escaped cellular genes became dominant in the thinking on the origins of viruses 62–64
Very recently, the study of fundamental aspects of virus evolution experienced a true renaissance that led to the proliferation of hypotheses and models that revolve around the concept that viruses were important contributors to the origin and evolution of cells 42, 44, 59, 65–70
. In particular, Forterre proposed the hypothesis of “three DNA cells and thee DNA viruses” according to which modern-type DNA-based cells evolved when three distinct DNA viruses displaced the original RNA genomes in three cellular lineages (progenitors of bacteria, archaea, and eukaryotes, respectively); the DNA viruses themselves are thought to have evolved as parasites of these primordial RNA cells 44
. However, as discussed above, RNA cells do not appear to be a viable proposition. Therefore, the alternative scenario that seems to reconcile the results of comparative genomics and the general logic of precellular evolution revives Haldane’s idea at a new level and involves evolution of diverse virus-like elements and even virus-like particles prior to the advent of modern-type cells 59
The emergence of cells is the epitome of the problems encountered by all explanations of the evolution of complex biological structures, the crucial conundrum of biology that was first recognized and explored by Darwin in his famous discussion of the evolution of the animal eyes 26
. Darwin’s solution, with some embellishments, has since become the standard scenario for the origin of complex systems: the intermediates might not be fit to perform the function of the final, complex structure but they are good enough for either a simplified version of that function or, perhaps, a distinct function that is not always easy to deduce from the present one. For the latter case, Gould coined the succinct term exaptation, that is, recruitment of a structure for a new function 71
. The virus-like early stage in life’s early evolution belongs to the same family of solutions and might be the most plausible if not the only way to avoid the ultimate “irreducible complexity” trap associated with the origin of cellular organization itself.
Like all biological evolution, pre-cellular evolution was undoubtedly driven, in large part, by natural selection. Selection enters the scene with the appearance of replicating entities, initially, it is currently presumed, RNA molecules replicated by ribozymes, and subsequently, after the emergence of translation, RNA molecules replicating with the aid of proteins 72, 73
. These earliest stages of evolution are beyond the scope of this discussion. It is important to note, however, that one of the central aspects of the model of a virus-like, compartmentalized, pre-cellular stage of evolution is a gradual transition from selection at the level of individual genetic elements to group selection for ensembles of such elements encoding both enzymes directly involved in replication and proteins responsible for accessory functions, such as translation and nucleic acid precursor synthesis 45, 74
Ensembles of “selfish cooperators” could potentially evolve by two routes: i) physical joining of genetics elements and ii) compartmentalization 45
. The former route is considered to be the onset of the evolution of operons including the ribosomal-RNA polymerase superoperon, the only substantially conserved feature of the genome organization between archaea and bacteria 75, 76
. The compartmentalization route would depend on the evolution of virus-like particles that could harbor (relatively) stable sets of genomic segments resembling the extant RNA viruses with multipartite genomes. Unlike cells, the virions of viruses with small genomes, particularly, the nearly ubiquitous icosahedral (spherical) capsids, are simple, symmetrical structures that, in many cases, are formed by self-assembly of a single capsid protein 77–80
. Thus, it is attractive e to speculate that simple virus-like particles were the first form of genuine, biological compartmentalization that were important at the pre-cellular stage of evolution. In addition to the benefit of compartmentalization, virus-like particles would protect genetic elements (especially, RNA) from degradation and could be vehicles for gene transfer within and between networks of inorganic compartments.
Most of the spherical viruses with relatively complex genomes possess molecular motors for DNA or RNA packaging within the capsid 79, 81–84
; at least in some cases, these machines also mediate extrusion of mRNA transcripts from the capsid 85, 86
. The viral packaging and extrusion machines contain motor ATPases of at least three distinct families that seem to share a common architecture, forming hexameric channels through which DNA or RNA is actively translocated 86, 87
. Notably, one of the groups of viral packaging ATPases is a branch of the FtsK-HerA superfamily that also includes prokaryotic ATPases responsible for DNA pumping into daughter cells during cell division 50
whereas another family is homologous to bacterial twitching mobility ATPases (Ref. 86
and EVK, unpublished observations). In membrane-containing virions of many viruses, the packaging motors translocate the DNA or RNA both across the capsid and the lipid membrane of the virion. It is tempting to hypothesize that viral packaging machines were evolutionary precursors of the cellular pumping and motility ATPases. Moreover, the H+-ATPase/ATP synthase, the key, universal membrane enzyme and the centerpiece of modern cellular energetics, also forms a similar hexameric channel 88
and might have started out as part of the packaging/extrusion machinery in a still uncharacterized (possibly, extinct) class of virus-like agents. Indeed, a recent comparative-genomic analysis has suggested that that the common ancestor of the two major branches of membrane ATPases, F-ATPases typically found in bacteria and V-ATPases characteristic of archaea and eukaryotes, evolved from a common ancestor that functioned as a protein or RNA translocase 89
. More generally, it seems an attractive possibility that primordial viral membranes were intermediate steps in the evolution of membranes that antedated the emergence evolution of the first cellular membranes, a major challenge in terms of evolution of complexity. Just as genome replication of virus-like agents can be viewed as the original test ground for replication strategies 42
, two of which have been subsequently recruited for the two major lineages of cellular life forms, evolving virus particles might have been the “laboratory” for testing molecular devices that were later incorporated into the membranes of emerging cells ().
From the selection for gene ensembles, there is a direct path to selection for compartment contents such that compartments sustaining rapid replication of genetic elements would “infect” adjacent compartment and, effectively, propagate their “genomes” 45
; primordial virus-like particles would have been important for this process. The pre-cellular equivalent of HGT, that is, transfer of the genetic content between compartments, is part and parcel of this model, in agreement with the general concept that rampant HGT was an essential feature of the early stages of life’s evolution 51, 53, 54
. After a substantial degree of complexity has been reached through the evolution of selfish cooperators within the networks of inorganic compartments, repeated escapes of cell-like entities that combined (relatively) large DNA genomes and membranes containing transport and translocation devices (originally evolved in virus-like agents, under this model) became possible. There is no telling how many such attempts have failed quickly and how many might have been initially successful but the fact is that only two, archaea and bacteria (assuming a symbiotic scenario for the origin of eukaryotes 90
), or three, archaea, bacteria and eukaryotes (assuming the so-called archezoan scenario of eukaryotic origin 91
) survived for extended time intervals (the scenario for the origin of eukaryotes is peripheral in this context and is outside the scope of this article). The first successful escapes of cellular life forms from the hypothetical pre-cellular pool would correspond to the “Darwinian Threshold” for cellular life postulated by Woese 51
, that is, the threshold beyond which HGT would be substantially curtailed, and evolution of distinct lineages (species) of cellular organisms could take off.
Like other models of the early stages of evolution of biological complexity, and perhaps, even more explicitly, the “primordial virus world” scenario outlined here faces the problem of takeover by selfish elements 74, 92, 93
. If the primordial parasites became too aggressive, they would kill off their hosts within a compartment and could survive only by infecting a new compartment (where they could be dangerous again). Devastating “pandemics” sweeping through entire networks and eventually wiping out their entire content are imaginable, and indeed, this would be the likely fate of many, if not most, primordial “organisms”. The conditions for the survival of pre-cellular life forms were, first, emergence of temperate virus-like agents that do not kill the host, and second, early invention of defense mechanisms, likely, based on RNA interference (RNAi). The ubiquity of both temperate selfish elements and RNAi-based defense systems in all major branches of cellular life 94, 95
suggests that these phenomena evolved at a very early, quite possibly, pre-cellular stage of evolution.
The primordial virus world model of pre-cellular evolution sketched here seems to offer plausible, even if, to a large extent, speculative solutions to many puzzles associated with the origin of cells. Comparative genomics of viruses and other selfish elements seems to provide substantial empirical support for this model. Considering that, under the primordial virus world scenario, the first cells emerged from a non-cellular ancestral state in multiple, independent escapes, it seems sensible to replace the acronym LUCA with LUCAS, for Last Common Ancestral State.