How Did Complex Life Evolve?

There has been life on Earth for some 3.8 billion years – but for a long time the life forms were very simple. For 1.8 billion years – so almost half the history of life on Earth – only bacteria and archaebacteria existed. Compared with other single-cell organisms such as paramecia or amoeba, or even multicellular organisms such as fungi, plants and animals, they have an extremely simple structure. Their cells consist only of a cell membrane that surrounds a lean survival kit containing the genetic information and proteins needed for growth and cell division, for simple sensory function and for gene regulation.

Life doesn’t get simpler than that. But this simple structure meant that bacteria and archaea – collectively known as prokaryotes – were also limited in their evolution.

Then, all of a sudden, the first eukaryotic cells emerged, which had a nucleus surrounding the genetic information. And from then on, evolution really took off: the cells became increasingly complex, developed new intracellular mechanisms, grouped together to form colonies and became specialized. And a diverse array of life evolved – from nematodes to dinosaurs, millions of species of insects and huge primeval forests to the mammals we see today.

“The transition from simple prokaryotes to eukaryotic cells was probably the most important step in the history of life on Earth,” says Jordi Bascompte, professor of ecology at the Department of Evolutionary Biology and Environmental Studies at the University of Zurich. Without this process, multicellular organisms such as plants and animals, but also we humans would never have been able to evolve in the first place. But how did this evolutionary jump from bacterial to eukaryotic cells come about and what was needed to make it happen?

This is not an easy question to answer. For nearly all other evolutionary developments, interim steps are found in the vast array of life forms which researchers can use to prove what happened. But for the evolution of eukaryotic cells – the basis of all complex life – there is no interim step. The well-known British biochemist Nick Lane from University College London wrote in his book The Vital Question: Energy, Evolution and the Origins of Complex Life about “a black hole at the heart of biology.” Jordi Bascompte and his team have now shed light on this black hole by analyzing the lengths of genes and proteins from thousands of organisms from the whole evolutionary tree.

Because besides the question of how the first eukaryotic cells arose, there is also a question mark over how the regulation of new, much more complex cells evolved. Eukaryotic cells do not only contain DNA and proteins floating around loosely, but organelles such as the nucleus or mitochondria and other “mechanisms” that allow the eukaryotic cells to perform specialized functions.

In addition, a cell that contains many more and such sophisticated components, must also be able to regulate them. Bacterial cells are unable to do so. A completely new method of regulation therefore had to be “invented” so that life could continue to evolve. Bascompte was able to show this in an interdisciplinary collaboration with computational biologist Enrique Muro from the Johannes Gutenberg University in Mainz, physicist Fernando Ballesteros from the University of Valencia, and Bartolo Luque from the Technical University of Madrid.

The researchers used computers to analyze the length and variance in the length of genes and proteins that can be found in specialized public databases. They started by looking at the genes, studying over 33,000 genomes from bacteria, archaea, fungi, invertebrates and vertebrates – nearly 150 million genes altogether. In a subsequent step, they analyzed the proteome – in other words, the entire set of proteins – from more than 9,900 organisms, some 55 million proteins in total.

Comparing these two analyses with the timeline of evolution of life on Earth allowed the researchers to make sense of the data and pick out the relevant findings.  This revealed that prokaryotes evolved to become more complex as their genes grew longer, and in parallel so did the proteins coded from these DNA templates. A large proportion of these proteins are responsible for genetic regulation, so for the synchronized activation and deactivation of genes, depending on what the cell needs at the time.

The reason for the growth in length is easy to comprehend: the longer the genes and proteins, the more possibilities for mutation arise and the more evolutionary potential a cell has. The researchers also showed that this process was mathematically multiplicative and happened in part through gene duplication, in other words the duplication of genes or gene segments.

“The prokaryotes could only evolve up to a certain point with this system,” explains Bascompte. In precise terms up to an average protein length of 500 amino acids, as their research showed. “Beyond that, growth in the length of proteins no longer gives rise to more evolutionary possibilities.”

Because the longer the proteins, the more energy-intensive and complicated the protein folding, and this is necessary for them to be able to perform their function. It therefore became impossible to find new solutions with larger proteins. “With this system, life simply hit a wall,” says Bascompte.

Up to this point, only proteins were responsible for genetic regulation – as is still the case with prokaryotes today. Eukaryotes are different. Here, too, the proteins stabilized at an average length of around 500 amino acids. However, the DNA continued to grow, as the analysis carried out by Bascompte’s team shows. It gave rise to what are known as introns – segments of DNA that did not code for proteins but took on a new function, namely gene regulation.

Introns, which had previously been labeled ”junk DNA” before scientists understood their function, can actually switch genes on or off. In addition, the mRNA transcribed from them is cut in the nucleus and then recombined in different ways, in a process known as splicing. This suddenly offered many more possibilities and therefore more evolutionary potential.

For aesthete Bascompte, the exciting and beautiful thing about this system transition is that mathematically it looks exactly the same as a phase transition in physics. Such as the transition from water to ice – from one state of matter to another.

Such phase transitions are among the universally applicable physical processes in nature. That is to say, they always work a specific way. And it was the same with evolution, as the mathematical relationships from his analyses show. Bascompte says: “To become more complex, there was no other way for life than to make this direct leap from one phase to the next.”

What’s more, the researchers were able to use the mathematical relationships on length and length variance in genes and proteins to map and predict these properties for all forms of life. They show that the growth in gene sections throughout evolutionary history is mathematically correlated with the complexity of life, with more complex life forms such as vertebrates having longer gene sections and more variance than simple life forms such as fungi. And this description takes us right back to bacteria. “It’s pretty crazy how this simple mathematical relationship in evolution led from the earliest forms of life to humans,” says Bascompte.

He sees these universally-applicable relationships as the real highlight of the work. “The fact that the transition from prokaryotes to eukaryotes and their further evolution is mathematically so simple and fits in with the principles of physics, helps reconcile the arbitrary nature of evolution with fundamental physical laws. That holds its own special kind of magic.”