Overview
While most origin of life researchers are focused on the evolution of self-replicating macromolecules (either gene-like structures or protein-like structures as we covered in our video about the RNA world hypothesis), other scientists believe that before macromolecules could originate, some aspect of modern cellular metabolism must have been present.
There are two main “Metabolism-First” hypotheses. Both concepts are based on the idea that some aspect of modern metabolism existed before the first macromolecules and helped to produce them:
Proto metabolic cycles (referred to in the literature as “autocatalytic sets”) are cyclical reactions that can grow. When 2 simple autocatalytic sets merge, they can develop new traits, some of which may help in their survival. It is proposed that autocatalytic sets may be capable of type of open-ended evolution and eventually gave rise to evolving macromolecules and then life as we know it.
Metabolic “fossils” can be found in modern metabolisms. Their study can reveal the chemical nature of the environment that first generated life, allowing us to simulate that environment and perhaps witness life’s re-emergence in the lab.
This animation is a follow up to the video “What is Metabolism?”.
Explore Further
Scientific papers on metabolic fossils (shown in this animation)
- A plausible metal-free ancestral analogue of the Krebs cycle composed entirely of α-ketoacids
- Linked cycles of oxidative decarboxylation of glyoxylate as protometabolic analogs of the citric acid cycle
Early work attempting to piece together a primitive metabolism from the study of modern metabolisms
Scientific papers on autocatalytic sets
Video lecture on autocatalytic sets
Popular Article on the general idea of metabolism-first
Transcript
Where does metabolism fit in the origin of life?
The mystery of the origin of life has not been fully solved. When we study cells (even relatively simple cells) we are mesmerized by the beauty and complexity of their macromolecules – things like genes and proteins – and by the complexity of cellular metabolism. Cellular metabolism is the sum total of all controlled chemical reactions performed by a cell.
When you eat and digest an apple, for example, bits of that apple are given to your cells through the bloodstream. Each cell’s metabolism then transforms those apple bits into new parts of the cell.
As you can see from this metabolic chart, even bacterial cells perform many carefully controlled chemical reactions.
Charles Darwin and those who continue his work, have clearly shown that the process of biological evolution (sometimes called “Darwinian evolution”) is able to create highly complex structures, and systems. The problem is, in order for biological evolution to work, you need to start with something that is able to make copies of itself and mutate. You need something capable of self-replication.
Most people studying the origin of life are working under the idea that macromolecules (strings of amino acids which are the building blocks of proteins, strings of RNA, or something similar) may have been the first self-replicators – rudimentary evolving life forms in and of themselves.
In our video on the RNA world hypothesis, we show that (under special lab conditions) chains of RNA can act as templates for their own replication. They can mutate. They can also fold up into 3 dimensional shapes, some of which can play an active role in their own survival! Many would argue that these chains of RNA, they are alive. That said, we don’t yet know how these evolving molecules would have gotten started on a lifeless planet. We’re not sure if they would be “prebiotically plausible”.
Under these “Macromolecule-first” hypotheses it’s often assumed that metabolism is not really something we need to worry about when we study the origin of life. Once the first evolving macromolecules adapted to, and in some cases evolved to cooperate with each other, this thing we call “metabolism” it was generated automatically.
It might seem odd that something this complex could be produced for free, but as an analogy: If you want to draw a zebra, you don’t have to draw the black stripes and then also draw the white stripes. White stripes simply come along for the ride.
For the most part, a metabolic chart like this one is showing us the chemical reactions caused by macromolecules as they interact with each other and small molecules taken in from the environment. This diagram just maps out how macromolecules cooperate. Biologists already understand how cooperation evolves between different organisms and we already know that macromolecules can evolve just like organisms. We don’t need a special explanation for metabolism.
The problem is, we don’t fully know how the first evolving macromolecules came to be. Before the Earth’s natural chemistry could have produced chains of amino acids or RNA, it likely needed to generate large concentrations of single amino acids or single RNA building blocks.
Experiments simulating various early Earth environments do produce amino acids, but they produce all sorts of junk alongside them. Scientists call this the sludge problem or the “tar paradox”.
Does this paradox exist because we are looking at the wrong types of environments with the wrong types of chemical reactions? Quite possibly! The early Earth (like modern Earth) was a huge place with millions of chemically unique environments. How could we possibly hope to narrow things down to find the right environment – one that might produce the building blocks of life in high concentrations?
This is where metabolism-first hypotheses are starting to help. Currently there are several wildly different metabolism first hypotheses, but they all have one claim in common: Some aspect of modern metabolism must have existed before the first macromolecules were produced. The idea that Metabolism came first!
Back to our analogy: The zebra might be at least partly black with white stripes instead of white with black stripes.
Some researchers are looking at what they call prebiotic autocatalytic sets. These are simple cyclical chemical reactions that some people claim might be capable of Darwinian evolution all on their own. This claim, however, has not yet been demonstrated.
Other researchers, such as Greg Springsteen and Ram Krishnamurthy, take a much milder approach. Instead of searching for simple chemical reactions that might be able to evolve on their own, they believe that the study of metabolism could help us figure out what specific types of environments could generate life. Their logic goes like this: If an ancient environment existed that was producing macromolecules (some capable of replication and evolution) natural selection would have favored any macromolecule that happened to be able to turn around and enhance the environmental chemical reactions that produced it (or it’s building blocks) in the first place. This behavior would increase that macromolecule’s chances of reproduction.
If this is correct, somewhere hidden among these complex charts of modern cellular metabolism, a rough outline of those early environmental chemical reactions might still exist—metabolic fossils! Understanding these reactions would help us understand the types of environments able to cause those reactions. We could discover the nature of the cradle of life!
This would be similar to an alien studying the chemistry, atmosphere and temperature inside a human spaceship, for clues about what it might be like on the planet that humans come from.
Several possible metabolic fossils have already been found. This was done by searching for metabolic reactions that are shared by distantly related organisms. Evolutionary logic tells us that widely shared traits are probably the oldest. The oldest metabolic reactions are likely most similar to the reactions that occurred in the environment where life first emerged.
One of these fossil candidates is the reverse Krebs cycle (also called the reverse citric acid cycle) which is commonly found in microbes. It’s a variation of the cycle in our own cells but is extra promising because it feeds on carbon dioxide and hydrogen. These molecules are super common on planets in our solar system, and would have been common on the early Earth.
The cycle binds these simple molecules to produce larger products. These are then captured by different metabolic pathways to build sugars, fats, amino acids, and eventually macromolecules.
Most reactions in the modern cycle are guided by highly evolved macromolecules – the very things we don’t think existed on the early Earth.
That said, Trent Stubbs, and his colleagues have carefully studied each step in the cycle and discovered a group of similar reactions that happen without macromolecules. They work in very mild conditions, produce almost every product made in the reverse citric acid cycle (including precursor building blocks for macromolecules), and all of this is done with very little waste. These reactions completely avoid the tar paradox!
This is a very promising start. The idea now is to either modify or combine this system with other metabolic fossils, to find a system that generates complete macromolecules from carbon dioxide hydrogen, and other simple starting molecules. Geologists could then figure out what types of environments could have supported this chemistry. We could simulate those environments in the lab and hopefully, witness the natural emergence of macromolecules that are fully capable of open-ended Darwinian evolution. These would be rudimentary life forms!
It’s a longshot, but it really might be doable.
So in summary, what is the metabolism first hypothesis? Well, there are actually several. Some are focused on autocatalytic sets, others on metabolic fossils. All of them are based on the idea that some aspect of modern cellular metabolism existed naturally in the environment before genes and proteins were ever produced.
