For life as we know it to emerge, RNA and peptide/protein molecules formed from nucleotide and amino acid building blocks must have become enclosed within lipid membranes to form the original basic cells or protocells.
As well as carrying information, RNA can also play an active role and drive reactions, with different sequences of RNA possessing different functions. RNA molecules that can catalyse reactions are known as ribozymes (ribonucleic acid enzymes).
In a random manner, protocells would have formed containing different combinations of various RNA and protein molecules. Through a process of evolution, protocells containing more advantageous combinations of RNA and protein molecules would produce more copies of themselves and be more successful. Over time, these protocells would have gained more abilities that allowed them to spread life across the Earth.
We don’t know what the first protocells looked like or what they contained, but scientists can try to recreate different possibilities in the lab to find out.
A successful protocell should have the capacity to carry out 3 basic functions: making more of the required building blocks, copying its functional RNA and protein molecules, and dividing in two to produce two new protocell bubbles.
We can break down how specific combinations of types of RNA and protein molecules and inorganic components present on the early Earth might have given protocells advantages in these 3 basic functions.
The functions
Making building blocks:
Metaboliser RNA
- Ribozymes that can make new building blocks from smaller chemicals
- Would build up a supply of food for a protocell
Metaboliser RNA + meteorite fragment
- As meteorites dissolve in streams, high energy phosphates leach from them
- Ribozymes have been shown to use these chemicals to supercharge building blocks so that they can be linked together easily
Metaboliser RNA + catalytic peptide
- A wider set of chemical groups has allowed proteins to replace RNA as the primary molecule driving reactions in our cells
- Our research suggests that RNA and peptides had an intertwined history in early life
- RNAs may have harnessed peptides to fine-tune their activities, starting the slippery slope to the architecture of modern biology
Catalytic peptide + iron-sulfur cluster
- Our cells use clusters of 2, 4, or 8 iron and sulfur atoms to carry out hard chemistry, stripping electrons from molecules
- We have shown how UV light could put together these clusters on the early Earth, arranged and activated by simple peptides
- This may unlock new chemical pathways to make more RNA building blocks
Copying its parts:
Replicator RNA
- Some ribozymes can build new RNA molecules, using another RNA molecule as a template and stringing together building blocks to copy the template
- They can even make copies of themselves
Meteorite fragment + sticky peptide
- RNAs are fragile and tend to break apart easily
- Sticky peptides may function to hold pieces together in a structural scaffold
- Catalytic nickel surfaces on meteorite fragments can generate chemicals that repair the RNA
Sticky peptide + replicator RNA
- RNAs can have trouble working together as they are negatively charged and repel each other
- A positively charged peptide can interact with both and bring them together
- We discovered that these peptides let RNAs copy each other in a model protocell
- Scientists think that RNA initially recruited peptides to help bring RNAs together for copying, before the wider chemical capabilities allowed proteins to take over from RNA
Replicator RNA + clay particle
- Clays form when water acts on volcanic ash – they are layers of atoms between which water and molecules can move
- Building blocks have been shown to line up on them and become linked together to make short RNAs
- We have shown how short RNAs can give replication a massive head start
Dividing in two:
Divider RNA
- Some RNA molecules can stick to other things
- Scientists have found an RNA sequence that can stick to and disrupt protocell surfaces
- The right shape might pinch a protocell into two new protocells
Divider RNA + clay particle
- As well as aligning nucleotides to produce new RNAs, clay particles can gather lipids to grow new protocells
- Divider RNAs could then release new protocells from the clay surface, allowing them to spread to new locations
Divider RNA + oily peptide
- Oily peptides can worm their way into the fatty surfaces of protocells
- By disrupting the surface, they could help absorb surface components from outside, growing the protocell and could build the tension that helps a divider RNA to split the protocell in two
- Oily peptides could even make a pore for molecules to diffuse in, giving a free supply of building blocks, in the right environment
Oily peptide + iron-sulfur cluster
- Oily peptides that help localise iron-sulfur clusters to the surfaces of protocells would allow chemistry to occur at these defined sites
- This could unlock new chemical pathways that help grow and expand these protocells
What we work on
The Holliger lab at the MRC Laboratory of Molecular Biology is interested in self-replicating ribozymes – both for their synthetic utility and relevance to the origin of life.
We have developed a ribozyme that can make RNA longer than itself, and one that builds a copy of itself from trinucleotide building blocks.
We have learnt that primordial RNA replicators behaved less like modern DNA polymerases and more like ribosomes.
We have also studied how our ribozymes benefit from other prebiotic components like simple peptides and protocells, or primordial environments like ice.
We are also exploring whether some of the hallmark processes of life, like heredity and evolution, can be performed by chemistries beyond the molecules we find on Earth, called “xeno nucleic acids (XNAs)”.
