Evolving molecules point to principles of life

Chemistry professor Sijbren Otto accidentally discovered evolving molecules. They are now the focus of his research. Ultimately, they may help us discover the general principles governing the origin of life. Keeping the molecules away from equilibrium appears to be key. Part 2 in a series on the Orgins Center, which will investigate how the Universe and life on Earth began.

Otto was working with a mixture of molecules when he discovered something exciting. The basic building blocks in the mixture, peptides, were designed to form rings. But the rings started to form stacks, which stimulated the formation of new rings. The stacks would grow and break, and the ends would start growing again.

‘This system had some very intriguing properties’, recalls Otto. For one, it exhibited exponential growth, which is typical for life. ‘Most other self-organizing molecular systems won’t do that.’ He also discovered that the type of ring that appeared in the experiment could be manipulated by either stirring or shaking the container holding the mixture. Further experiments showed that the stacks could exhibit a form of ‘ speciation ’, which depended on the building blocks (the ‘food’) present in the mixture.

Death

Of course, self-organizing molecules in a test tube are not ‘alive’, and Otto refers to them as ‘replicators’. But how would he define life? ‘The American space organization NASA defines it as a self-sustaining chemical system capable of Darwinian evolution’, he answers. ‘But I would want to refine that and say it should be capable of open-ended evolution.’ This means that the system must be able to invent totally new possibilities, rather than merely shift within the limits of some pre-defined variation, which is what qualifies as Darwinian evolution.

His own system doesn’t qualify for this refined definition. ‘The variation is too limited. Nevertheless, we do have mutation and selection. We’ve introduced a kind of death, the destruction of the stacks. This makes the system dynamic. New stacks are formed by the building blocks – which are like food providing energy – and then destroyed, as happens with all life.’

Such a system, which is out of equilibrium, produces different replicators from a system that is in equilibrium. ‘Equilibrium is a show stopper: nothing interesting happens in that state. You won’t get increasing complexity from such a system.’ Most work in chemistry is done with stable molecules. ‘But that is not how life works! There is a lack of appreciation for the importance of instable, out-of-equilibrium processes.’

Delicate

In March of this year, Sijbren Otto was awarded an ERC Advanced Grant for his work on chemical evolution. He also belongs to a European network of chemists who are interested in the origin of life. Given his interests, it is no wonder that Otto is at the forefront of the Origins Center, which aims to find out how the Universe and life began. How close are we to creating life from lifeless matter? ‘We need to take a few more steps to achieve open-ended evolution’, says Otto. He smiles: ‘But it might require a geological timescale for a system to take those steps.’

Then again, it may not take that long. His artificial system delivers rapid results, so the open-endedness might surface any time. ‘Sometimes it feels as if progress is very slow. We are taking small steps all the time by adding new building blocks one by one.’ He laughs. ‘Maybe we should add 30 new ones in one go and see what happens.’ But the analytical side is complicated, so taking such a leap is not something you do on a Friday afternoon.

‘Achieving open-ended evolution is a delicate process. If you give the system too much room, too many degrees of freedom, it won’t go anywhere, but if you restrict it too much, it won’t go anywhere either.’ So Otto has to find the sweet spot, without knowing which mechanisms or conditions really make the system creative. Biology gives a hint though: ‘Biological evolution is fast when conditions are variable, so we try to put some pressure on our systems.’ And he may try adding components other than peptides. ‘We could feed it with the building blocks of DNA or with lipids as well. This might result in new types of replicators.’

Time

If his system does achieve open-ended evolution, what will it say about the origin of life on Earth? ‘We will never be certain how it happened’, says Otto. ‘But if we succeed in creating life, that would answer some very important questions.’ First and foremost, it would show that life can indeed originate from lifeless matter. ‘And we would discover which mechanisms cause life to originate. If these mechanisms turn out to be general ones, it would give us a clue about how life on Earth started.

Otto thinks he can already identify two general principles: ‘You need to concentrate materials. In chemistry we use phase separation to achieve this. And you need autocatalysis, reactions which amplify themselves. That’s how you achieve the exponential growth you see in living systems.’ It is likely to be a matter of time before these principles create new life in a lab somewhere. But how much time is the big question.

This is the second part of a series on University of Groningen research into the origin of life and the Universe.
Part 1: New research centre on the origins of life, the universe and everything

Part 3: Synthetic biology: building life
Part 4: The mystery of life’s broken symmetry
Part 5: Life amongst the stars
Part 6: Origins on a computer

See also: Otto Research Group website