In my previous post, A brave new RNA world, I looked at how the RNA world hypothesis is the leading explanation for how cellular life managed to emerge – and, accordingly, how complexity managed to increase to enter into a new regime of order. Life, as it seems, took a ‘building blocks’ approach to getting here; it passed through a Ribonucleic acid (RNA) stage (and perhaps others before it) before taking cellular form. However, it needed for certain conditions to be met in order to animate those ribosomic building blocks into, well, life. I spoke to Australian National University Associate Professor Rowena Ball, who leads an international research project addressing origin-of-life questions, about these conditions.
She told me that there needed to be some kind of external energy source to enable RNA to replicate without cellular machinery powering the process, and one which fit within the criteria imposed by the rules of thermodynamics. Such criteria necessitated the presence of a form of thermal cycling – a periodic energy source which produced a heating phase to separate the RNA’s base-paired double strands and a cooling phase to anneal both strands into a double helix.
This was just the sort of problem which Ball and her colleague, Leeds University’s Professor John Brindley, were fit to deal with. Both were applied mathematicians and some of Ball’s previous work looked at the suitability of safety standards of using highly energetic reactive liquids. For instance, Ball explained to me that these reactive liquids, “can start to decompose and undergo this oscillatory instability, which can be quite violent and is often the reason – rather than classical ignition – for sudden… liquid explosions”. As a result, Ball was well-acquainted with the concept of a “thermochemical oscillator”, an exothermically-reacting chemical system that gave off a periodic temperature response. If the volatility of highly reactive liquids came about through vacillations in their thermal chemistry – their enthalpy – then it was possible RNA replication could have been energised by a similar kind of oscillator.
A 2012 study conducted by three German researchers at Ludwig Maximilian University of Munich provided a bit of a light-bulb moment for Ball and Brindley. By using artificial thermal cycling in the lab the authors successfully replicated and amplified a short RNA segment, derived from a bacterial-transfer RNA. “They waved their arms and said, ‘the convective cycling in porous rocks in undersea hydrothermal vents in the primordial ocean, between hot and cold sides of these pores, provided the necessary thermal cycling’,” Ball recounted. “We looked at that and immediately said: ‘thermochemical oscillator!’”.
Equipped with the results of the work Ball had done with various other researchers on oscillatory thermal instability, she and Brindley started thinking about the role a thermochemical oscillator could have played in providing the periodic thermal cycling described in the 2012 study. “We settled on the hydrogen peroxide-thiosulphate oscillator, by looking at what was likely to be available in the primordial soup, and so on,” Ball said. “We set up a simulated experiment in the computer and ran it and put in the short RNA strands, and put the kinetics and all the parameters we needed. It worked first go, it worked like a dream.”
In 2014, Ball and Brindley published their findings for the first time in a paper for the Journal of the Royal Society Interface. They had established hydrogen peroxide, combined in an exothermally-reacting system with thiosulphate, as a candidate for the producer of the thermal cycling required to energise the RNA world. This year, they published another study on the hydrogen peroxide oscillator, and are close to finalising the publication of two others (see here). In these subsequent papers, the pair have consolidated their theory by linking the hydrogen peroxide to two other unsolved mysteries about the chemistry of life.
One of those mysteries, the origin of the proton motive force, also dealt with one of the fundamental ways organic life managed to power its complex behaviour. First conceptualised by Peter Mitchell in 1961, the proton motive force wasn’t taken seriously until over a decade later and Mitchell eventually won the Nobel Prize in Chemistry for it in 1978. It is now understood as the process which powers all life and the processes that are essential to it, like respiration and photosynthesis, and it is generated by an electrochemical, or acidity (pH) gradient that forms across cell membranes. (For more on chemiosmosis and ATP, see here.) According to Ball, “the proton motive force is just ubiquitous across all life and as far as we know it always has been – no one can find an ancient organism that didn’t use it.”
“The big question is: where did it come from? Why pH gradient? Why not something else?” Ball asked, rhetorically. “Well, the answer is, it was always there. It was even there in the RNA world.” As well as being a thermochemical oscillator, hydrogen peroxide is a pH oscillator, and can therefore also account for the later presence of the proton motive force. If there was a hydrogen peroxide supply within the rock pores in which prebiotic nucleic acids abounded, it’s entirely possible acidity waves emitting from its pH oscillations galvanised them into action.
The second dilemma Ball’s latest studies have purported to shed light on related to the enigma behind the presence of homochirality in organic life forms. Many molecules happen to be chiral: they come in two forms of three-dimensional shapes, both nonsuperimposable images of each other, labelled “D” and “L”. (The same way your left hand is a nonsuperimposable copy of your right hand.) Curiously, the nucleic acids that make up DNA and RNA are exclusively homochiral: they’re all D-shaped. This phenomenon has stumped biologists and chemists for generations, and has led them to ponder whether this was an essential property of life or whether life on earth evolved having selected it. The prevailing idea is that, with structure being crucial to the correct functioning of both DNA and proteins, homochiral molecule designs were somehow needed to evolve operational life forms.
“The big mystery is how this breaking of symmetry occurred,” Ball said. “There are very few [forces] that we know of that drive chiral selectivity, and they’re very, very weak.” In fact, there are three of these chiral forces that have been known to scientists. One was circularly-polarised light. “So one theory is that in our part of the universe, there’s more circularly-polarised light in one direction than the other and that drove the formation of more D nucleic acids on the comets that brought them to Earth,” Ball explained. “And that would suggest that in another part of the universe, there’s more circularly-polarised light of the opposite chirality, and there could be L life in another part of the universe.” Another discovered chiral force has been the electro weak force, a fundamental law of physics which occurs throughout the entire universe. However, according to Ball, it is so weak that it would take until the end of the universe for it to cause any chiral selection.
The other chiral force: hydrogen peroxide. The candidate for the lifeblood of the RNA world happened to be the smallest, simplest chiral molecule, and it has been detected in interstellar space and throughout the solar system. “Chiral stuff begets other chiral stuff. So, for the first time we’ve got a chiral force that, in principle, can actually do the job,” Ball said.
So what does this all mean for rising complexity? In my next blog, Crossing the organic threshold, I reflect on what my conversation with Ball has taught me about the emergence of life and how it was enabled.