Evolution is full of chicken-and-egg scenarios, but one of the trickiest to solve is whether life existed before there was nucleic acid.
Researchers have now provided evidence of primitive biochemistry occurring without phosphate – an essential component of the nucleic acid building blocks of our genetic chemistry – adding fuel to the argument that before there was life, there was metabolism.
Scientists from MIT and Boston University have identified a number of alternative metabolic pathways that have no need of phosphate – and the findings could fill a gap in our understanding of how complex organic chemistry evolved into life on Earth.
Life as we define it today is largely based on imperfectly replicating chemistry – something that requires both a template that can be copied and the means to capture enough energy to physically rearrange simple carbon-based chemicals into more complex forms.
The question is which came first: a chemical code that could evolve in complexity, or complex pathways that could use energy to turn simple chemicals into complex organic compounds.
In the so-called RNA-world hypothesis, strings of free-floating ribonucleic acid (RNA) facilitated processes we might describe as precursors to life, with the polymer taking on the roles of both an early kind of information template and chemical machinery.
One problem with this concept is that RNA can't do its thing without an energy source, which would require a sequence of chemical reactions we could think of as an early form of metabolism.
Not only that, but the RNA molecule includes phosphate – a molecule that was locked up tight in the environment and was therefore difficult to incorporate into organic compounds.
Other 'pre-life' hypotheses suggest early forms of metabolic chemistry were already absorbing energy from the environment – in the form of heat or light – and transferring it from one chemical reaction to another in an organic soup unfettered by cell membranes.
Eventually, this primitive metabolism became coupled with RNA, before over time finding shelter inside individual fat-bubbles; objects which we could consider to be the first cells.
Metabolism in modern organisms, however, is largely based around compounds such as adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide phosphate (NADP), which once again include that troublesome old phosphate molecule.
The alternative metabolic pathways that have now been earmarked by the researchers are based on molecules built using sulphur, which would have been abundant in Earth's oceans several billion years ago.
"The significance of this work is that future efforts to understand life's origin should take into account the concrete possibility that phosphate-based processes, which are essential today, may not have been around when the first life-like processes started emerging," said researcher Daniel Segrè from Boston University.
The idea of sulphur taking centre stage of early metabolism isn't new – the early 20th century German chemist Günter Wächtershäuser suggested compounds of iron sulphide and nickel sulphide could act as catalysts for carbon fixation around deep ocean volcanic vents, acting as a simple metabolism for what he called "pioneer organisms".
As convincing as the chemistry sounds, solid evidence linking the variety of reactions involved in this 'iron–sulphur world hypothesis' has previously been somewhat scant.
"What was missing until now was data-driven evidence that these early processes, rather than scattered reactions, could have constituted a highly connected and relatively rich primitive metabolic network," said Segrè.
So Segrè and his team applied computational systems biology – a theoretical approach that uses mathematical models to explore diverse branching pathways of biochemical reactions – to identify a set of eight phosphate-free compounds that would have been abundant in our ancient oceans.
They then applied an algorithm to simulate primitive metabolism based on these chemicals, which included iron-sulphides and sulphur-containing compounds called thioesters, allowing them to evaluate how a bunch of different reactions might have occurred.
The researchers found that a core network of 315 reactions involving 260 metabolites could support the production of a vast range of complex organic compounds necessary for life, including amino acids and carboxylic acids.
Since early biochemistry failed to leave much evidence in the way of fossils, we're left to put together what pieces we can with mathematical models such as these.
While this isn't proof-positive of a phosphate-free kick-off to life, it does add evidence to the possibility that life emerged from chemistry most organisms no longer rely on.
And the applications of this kind of research stretch far beyond considering how early life might have formed.
"The idea of analysing metabolism as an ecosystem-level or even planetary phenomenon, rather than an organism-specific one, may also have implications for our understanding of microbial communities," said Segrè.
This research was published in Cell.