Portal de Periódicos da CAPES

The mark of metabolism: Another nail in the coffin of nucleic-acids-first in the origin of life?

2014; Wiley; Volume: 36; Issue: 3 Linguagem: Inglês

10.1002/bies.201400014

1521-1878

Andrew Moore,

Microbial Metabolic Engineering and Bioproduction

Andrew Moore Editor-in-Chief Many people still believe that the quintessence of life is the replicative ability of a genetic code. I have argued against this before 1, and now comes a second opportunity to do so. I craft my ammunition from an article in this issue that – in its essence – turns the Central Dogma (CD) of molecular biology on its head 2, placing metabolism, not DNA, at the head of the show. Put crudely, DNA records the selective drives and evolutionary history of metabolism. It's taken a long time to reach this point of reversing the CD, and that is not surprising, because the CD itself has framed the wrong question for us, namely "if DNA > RNA > proteins, what comes after proteins?" But a corollary of this reversal – from the dawn of life – has been tickling the fancy of geobiologists and evolutionary biochemists for a decade or so, and it has to do with the energetics of life. If one subscribes to the notion that life is only life because it creatively manages energetic fluxes (in the sense of the second law of thermodynamics) to produce a characteristic order, then life might well have arisen in the context of an inorganic energy gradient: specifically a chemiosmotic gradient that could be harnessed by structures – in this case, simple organic membranes – that formed from substances in the vicinity of the gradient 3-5. In this theory, the gradient results from a pH difference between the more alkaline water issuing from medium-temperature hydrothermal vents on the sea bed, and the less alkaline sea water – much akin to the proton gradient across the mitochondrial inner membrane. To put this into a larger context that brings us up to the present day: life needs energy, it manages energy in a special way, and that management is achieved by metabolism. Note, we have not yet invoked a genetic material; that will come later. But why should I be so convinced of the consistency between de Lorenzo's thinking and that of the evolutionary biochemists and geobiologists? Perhaps it is because evolution tends to leave marks of its very ancient workings. Real-time dynamics of a biological system have a habit of being closely related to the evolutionary dynamics of the system's origin, sometimes even mirroring them. One particularly striking example is developmental biology, in which evolutionarily more ancient structures appear earlier, and evolutionarily more recent ones later, during embryogenesis. Some structures – e.g., the vertebrate tail – even develop, only to disappear later. Somehow evolution has "trapped" the organism into developing in a particular way. And what is true of whole organisms is also true of protein molecules, as an article in our February issue describes 6: put simply, residues that contribute crucially to stability in a protein's core, or to binding with another protein molecule at their interface in a protein complex, tend to be evolutionarily highly conserved, and relatively static in molecular dynamic terms: they change identity little over evolutionary time, and they move little in real time. Conversely, residues in flexible loops tend to have high mutation rates across evolution: their identity is relatively loosely constrained by selection, and they are also rather free to move about in real time. In terms of metabolism, the reversal of the CD could be considered the "memory" of the initiating role of energy management in the origin of life. In coining the term "selfish metabolism" – as a replacement for the CD's "selfish gene" – de Lorenzo is not merely poking fun: as he notes, metabolic considerations dictate the behavior and "strategies" of microorganisms as they scour the "chemical landscape" for energy-bearing molecules in situations as diverse as environmental bioremediation and human infectious disease: inefficient conversion of an energy-bearing compound into "bioavailable" energy creates oxygen radicals that directly mutate DNA, hence stimulating the genetic exploration process for protein enzymes that more efficiently metabolize the compound. Are genes running the show here? It seems not. In fact, much of the "show" of primordial life can probably be performed without a genetic material: giant lipid vesicles, or "protocells," are capable – under particular conditions – of growth, division and fusion, and even competitive evolutionary processes and nutrient uptake (as reviewed in 7) merely by invoking physicochemical phenomena, i.e., in the absence of a replicative code. Reproduction is, after all, not the same as replication; rather it signifies the creation of a new biological entity that bears a close resemblance to the original. It also seems to be a biophysical phenomenon of the most primitive kind if it can even be performed by "lifeless" vesicles in the laboratory. Regulation of reproduction, on the other hand, requires a protein machinery, and because of the complexity of proteins compared with simple organic molecules, it appears that only a genetic code could accomplish that during evolution. Reproduction is a process that relies on a very special management of energy fluxes: it's not at all akin to the equilibrium chemistry of template-based replication. Rather it produces a new organism, and one that is largely free of damage compared with the parent (as discussed in 8); it exploits forced energy fluxes to produce local decreases in entropy (increases in order). This is a signal characteristic of life, it requires energy metabolism, and – in order to evolve – a selfish one at that. Andrew Moore Editor-in-Chief