The Tree of Life

Like many people, I’ve always been interested in nature, in the beautiful creatures around us, when we go walking in a forest or when we see all these different creatures. For most of human history, people didn’t really ask whether there were common ancestors. The first person to wonder whether, despite all the diversity of life on Earth, there are any commonalities, some sort of common relationships, was Charles Darwin.

In his notebooks, he had a picture of a tree, and he used this metaphor that all living organisms are branches on the tree and they all join up and there’s one trunk. He imagined in his sketchbooks that there was this single trunk to life on Earth. And we now know that his intuition was correct. Once upon a time, there was one organism and that organism gave rise to everything on Earth. In a way, you could look at all life on Earth as one colony. So, just as each of us starts as a single cell and gives rise to a whole body, the whole of life on Earth began as one cell, and is descended from a single cell, and that cell grew and divided, and grew and divided, and gave rise to the whole of life on Earth.

Where we really come from

Darwin was the first person to really say that all of life on Earth originated with a single organism that gave rise to everything else. And we now know that this was correct. All of life did come from this one event, descendants of this one event. But we also know that life on Earth comes in different forms.

There are simple cells like bacteria which are very different to “us” – humans, plants and mushrooms, different kinds of animals, whales, mice. There are different groups and we clearly look different. So, the question was: Where do we come from? Where did these complex organisms like us, which have incredibly complex cells, come from? And that started to be solved when people began to read that the code underlies how we are making all the DNA code. DNA is information, which is a code in each of our cells, and it can be read out. It’s a series of letters: A, T, G and C and you can actually read them. And because all life on Earth is related, we all share the same code. We can actually read the code of any organism. And what we see when we read the code of all these different organisms in life on Earth is that, first of all, that’s how we know they’re related, because they all have core things that they share. We all share different bits of information. We share machines that have survived 3 or 4 billion years of life on Earth that are the same. But there are some things that are differences, which make us different to chimpanzees and make us different to bacteria. And when you look at these differences, what you can see is that life on Earth splits into two big groups.

Two partners gave rise to all complex cells

There’s bacteria and there’s the other group of organisms called archaea, which are simple, very small bags with a bit of genome in the middle – with DNA in the middle – which codes what they do. And they often live in very extreme environments such as Yellowstone National Park, in hot sulphurous pools. There are some in our guts, but they weren’t really studied for a long period of time, only being discovered in the 1970s. But if you look at all of life, you realise that all of life on Earth is made up of bacteria and archaea. The question then becomes where do all complicated organisms come from – like us and whales and mice and plants? And when we look at the DNA – the information inside complex cells – there is a hybrid: we are actually all composite organisms. We are a mixture of bacterial genes and these other organisms called archaea. And that there are probably two partners that gave rise to all complex cells. In fact, all complex cells are also related. So, we are related very closely to plants and animals and mushrooms. But they come from a single cell again, like all of life comes from a single cell. There was another cell and that cell was a merger of a bacterial cell and archaeal cell.

That’s what Darwin didn’t realise: that it’s not about competition. This was a collaborative venture between two organisms that came together to work together to do something extraordinary that no living thing had ever done before. We just take one simple cell and another simple cell and make a complicated cell out of it. The problem, though, is that this happened around 2 billion years ago. So, if you want to go back in time and ask how it occurred, that’s going to be hard without a time machine. What we need to do again is think hard and look at the genome and try to deduce.

How simple cells give rise to complex cells

It’s clear that on Earth there are very different kinds of organisms. There were bacteria and there were archaea, and they were complex cells, which included us, plants, mushrooms or large complicated structures. The cells are also different: archaea and bacteria are both simple organisms which have a single bounded membrane with a bit of information inside, which is the genome which encodes the code that gives rise to the shape and the behaviour of that organism. And in our complex cells, there’s a composite of these two genomes. So, there’s information on the bacterial side and the archaeal side. But the question is because the cells are really simple bacteria and archaea, how do they give rise to a complex cell? And it is the question that has interested biologists for a very long time.

The first person to really help to show the way was Lynn Margulis, a famous scientist. She pointed out that in our cells, which are complex, there are structures which are the energy centres of the cell, these powerhouses called mitochondria, and these parts of our cell, mitochondria, actually look a bit like bacteria. She proposed that once upon a time these were bacteria. And what we now know is that genomes even contain a little bit of DNA themselves and that really marks them out as being bacteria that live in our cells. We now think that the bacterial part of their collaborative venture that became us was a bacterium. So this bacteria was taken up – maybe swallowed or engulfed or incorporated into the hole – and it persists as a little small structure, a tiny organelle which sits there and generates the power required for cells to work.

What about the rest of the cell? Where does that come from? This is a long mystery, partly because the other partner is an archaeal cell and we don’t know much about archaea. My lab is thinking hard about what the archaeal partner might have brought to this venture that is the complex cell, over a billion years ago. Scientists have to do a combination of looking at data and – especially when you think about the past – to theorise, to have an idea that you want to test.

The inside-out theory

In 2014, together with my cousin David, an evolutionary biologist, while I’m a cell biologist, we worked to come up with a theory which David labelled the inside-out theory. And the idea is that once upon a time, there was a simple archaeal cell that was sharing resources with a bacterial cell and that was the beginning of this collaborative venture – sharing resources. We imagined that this archaeal cell generated protrusions, structures that come out of it, that enabled it to capture more and more of these bacteria, to share more resources by shared interfaces where they would wrap around each other. And as those grew and grew, they led to these engulfed proto mitochondria – these bacteria being surrounded by this archaeal cell – and through a growing intimacy and the development of new machines that would, for example, allow cell-cell fusion or bits of the membrane to diffuse, you ended up with a complex cell. And this was just an idea, but it fitted a lot of the facts that we know about life on Earth and about eukaryotes – complex cells. But it’s just an idea, so we had to set about testing it. And we realised that the key way to do that was by studying archaea, because that’s what we don’t know about. And archaea probably gave rise to the host. And so, what my lab has been doing ever since then has been trying to study archaea to really look at their biology and how they work and try to therefore understand how they might have changed during the course of evolution to give rise to the body of ourselves.

The discovery of a new organism

In 2015, an exciting thing happened when a group was looking for organisms in places that had never been searched before. At the bottom of the sea, off the coast of Norway, two kilometres down, two metres under the seabed, they took a sample, which they could then extract DNA from. They couldn’t get cells because it’s hard to bring cells up. Potentially, they got what’s called a metagenomic sample: it’s a mix of all this information and all the organisms that live there. And they use clever techniques to assemble the genome and then they can see what organisms live there. And what they found, which is quite amazing, is a new organism that nobody ever discovered before, which was an archaeal cell. Incredibly, it looks like it’s actually our closest relative in the archaea.

So, it’s a living relative of us, but it’s archaeal, and it had many of the genes that we thought make a special many of the bits of information in humans, for example, that make us think, make us special, that enable us to do particular things. It turns out this organism that no one’s seen at the bottom of the sea has some of the same genes, which means that there is really a clear link now between much of the thing that makes our cells, gives them their structure and archaea, which is what my lab was working on, but unfortunately we couldn’t see it. And you can’t deduce cell shape from a genome sequence, because the genome, the DNA, doesn’t code for how to make a cell like how to make furniture. It’s not an instruction manual. It tells you how to grow a cell and divide in two, but you can’t really tell what it looks like. You can just get a sense of how that genome might do things. So, we really wanted to see it – and lots of groups tried.

Portrait of an organism

This year, a group in Japan, Imachi and Nobu, were able to do it. It turned out that 12 years ago they did a similar experiment off the coast of Japan: they collected stuff from the seabed, they tried to take it up, they tried to culture. What they found after this heroic 12 years of effort is that they got a culture and they were able to picture an organism. What was really amazing is that they didn’t find one organism because archaea don’t live alone, they actually live as symbionts. which is now part of a family called Ascot Archaea: there’s Loki, Heimdall, Thor, named after the Nordic gods. They live with other organisms. So, they found this organism and discovered that it lives as an obligate: it has to live with another organism to share resources to live. They took a picture of it, with electron microscopy, and the picture looked quite like the cell we had drawn in our theory of an archaeal cell that grows protrusions to enable it to touch other cells, to share resources as a first step in becoming a complex cell, a sort of complex community, which is what our cells are like.

And so this is the direction my lab is continuing to pursue to try to find out how the next stages happened and to sort of flesh out this idea. What we’ve discovered in that research recently, for example, is that there are many aspects of archaeal biology that really are very similar to our biology. So, although we’re separated by billions of years, these are single cells, tiny cells, the ones we study from the thermal pools in Yellowstone National Park. They grow at 75°C in sulphuric acid, but if you look at them with the right eyes, you’re looking to see what they share with us. They share a lot of biology with us. We really think that by studying them, we can learn much more about ourselves.

The key to understanding ourselves better

So this is all about the past. Why? Why is this interesting? Well, one thing is that these archaeal cells make up a huge swathe of life on Earth. We know nothing about them. They’re not yet known to cause disease. They live in our guts, but a huge amount of what happens on Earth is the job of archaea – the carbon cycle, all these sort of things – so we need to know about them. Archaea are, in fact, really simple, but like us, they serve as great models for studying the fundamentals of how cells work. If you want to study something like a human cell and understand how it goes wrong in cancer, it’s incredibly hard because our cells are these elaborate machines that are being refined again and again over billions of years. Archaea are simple ancestral forms that gave rise to all this complexity. And so, by going back, they’ll do something with one machine that we do with ten. But their one machine has to do everything that all our ten machines do. By studying them, we get a window into the principles of biology, how molecules really do things – like divide cells in two. It’s interesting to know where we come from, but it also provides an opportunity to know how the machines that are 2 billion years old, which we’ve inherited from them, work at a fundamental level.

Discover more about

the origins of life

Dey, G., Thattai, M., & Baum, B. (2016). On the Archaeal Origins of Eukaryotes and the Challenges of Inferring Phenotype from Genotype. Trends in Cell Biology 26(7), 476–485.

Baum, B., & Baum, D. A. (2020). The merger that made us. BMC Biology, 18(72).

Baum, D. A., & Baum, B. (2014). An inside-out origin for the eukaryotic cell. BMC Biology, 12(76).

Cancer: the selfish cell