How an ancient virus made our brains complex

An ancient viral infection may have given animals the tools to become fast, coordinated and smart, a study has found.

According to a paper published Thursday in Cell, complex nervous systems arose in the distant past after viruses inserted bits of code into the genomes of vertebrates — animals with a spinal cord, from humans to frogs to salmon.

In and of itself, this “invasion” is unremarkable; the insertion of such code is the major way that viruses — which have no ability to replicate themselves without the support of a sheltering cell — force cells to do their bidding.

But in this case, the cells turned the new code to their own ends — a dynamic that scientists have also found at the root of core animal activities such as fertilization and pregnancy.

“The cells got sick, and the cells thought — ‘We can use this sequence for our own purpose’,” said co-author Tanay Ghosh of the Cambridge Institute of Science.

The new bits of injected code helped guide the cellular machinery to produce myelin — a protective sheath around nerve cells that helps speed up the transmission of the electrical signals by which our nervous systems function.

Myelin in our nervous system works a lot like the plastic insulation that coats a fiberoptic cable: By blocking a signal’s ability to escape through the walls of a wire (or a nerve fiber), it allows that signal to be transmitted faster and with fewer mistakes. 

In evolutionary terms, this property allows for other potent effects.

Because myelin lets nerves transmit more quickly, it also allows new forms of simultaneous communications. And that enabled the evolution of complex neural networks that feature more connections and more interactions within a given amount of space. (While not all nerve cells have myelin sheaths, those that do — particularly in the white matter of the brain and spinal cord — are in areas where speed and density of connections are crucial.)

Without those faster signals, Ghosh said, “all the predator and prey mechanisms — all that huge diversity — would not have been developed.”

The team’s research found that the infection of ancestral vertebrates by myelin-coding viruses likely happened many times, as the closely related family of viruses modified the genomes of the ancestors of today’s fish, amphibians and mammals — each of which repurposed the new lines of code to build complexity. 

This required a complex evolutionary dance. The viral infection didn’t code for the production of myelin — another mutation did that. Instead, it helped the proteins that read and interpret the genome to bind to the precise region where the instructions for myelin can be found.

Scientists know this because some simple vertebrates — such as the sea lamprey — have the mutation for myelin but don’t have that added bit of viral genome. And the sea lamprey’s comparatively simple nervous system also has no myelin. Ghosh compares this primordial nervous system to an orchestra waiting to begin playing. “All the musical instruments were there, but they needed the trigger. The violins — or the viruses.”

These ancient viruses didn’t intend to change the structure of their hosts, Ghosh emphasized. Instead, the way this evolutionary concert played out shows something about cells that laypeople often miss.  

“Cells are smart,” he said. “They have a lot of mechanisms that we don’t understand — we don’t know how they’re doing everything. Sometimes we say they’re too smart for us.”

In a very real sense, the word “cell” — derived from the 17th-century discovery that plant and animal tissues were made of what appeared to be tiny boxes — doesn’t really capture the complexity of how cells interpret and react to every aspect of their environments. A box of molecules and tiny organs shoved into a microscopic envelope of fats isn’t enough to make a cell, Ghosh said. “You need to have many other things.”

This complexity plays out in a wide range of domains: in the highly efficient means by which cells make and maintain the systems that provide our bodies with energy, and in their careful self-pruning to find and fix mistakes in their code. All of that points to the idea that cells don’t keep around “waste,” Ghosh said. “If there’s something they don’t require, they just throw it away.”

This idea has stark implications for the human genome at large, about 8 percent of which is made up of strings of such ancient injected viral code, according to the Proceedings of the National Academy of Sciences.

Much of this code may also be functional — or have been repurposed by animals to do new things, many surprisingly intimate. Viral-derived DNA, for example, help form the placenta, which holds the fetus in most mammals — as well as a similar structure in marsupials, and another in a species of lizard that gives birth to live young. 

Humans and other primates also use repurposed viral DNA to help regulate a hormone that controls the timing of birth. And at the other end of the pregnancy process, viral DNA seems to govern the crucial transition by which the newly fertilized cells of an embryo morph from being able to create any structure — including those outside the fetus’s body, like the placenta itself — to becoming dedicated to building the fetus itself. (This stage happens a few days after fertilization, once the new one-cell embryo has repeatedly divided to create a several hundred-cell blastocyst.)

In order to make their way down to us, these changes couldn’t just happen in the bodies of individual animals. They had to somehow work their way into the “germ line”: a potentially immortal progression of sperm and egg cells that encodes — and is passed on by — the cells that make up the bodies of individuals. 

This process of infection, repurposing and transformation isn’t confined to our species’ ancient history, Ghosh noted — it’s still going on, with unknown future results. “In the future, more things can happen to our DNA — we don’t know,” Ghosh said. 

“Evolution is long,” he said. “It’s a dynamic process, not a fixed process.”