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This gene helps prevent cancer. Did it also give rise to all complex life?

🕐 4 min read

How did life get so complicated?

No, really. Molecular biologist Erik Hanschen would like to know. For billions of years, life on Earth was incredibly simple: Various single-celled organisms floated around the Earth, procreating, eating, avoiding getting eaten. It wasn’t super exciting, but it was also fairly easy, as far as living goes.

Then, some 800 million years ago, individual cells started grouping up. They collaborated, differentiated, grew in size and ability. Some sacrificed themselves for the good of the many. Compared to the long, dull years of single-celled living, the resulting diversification barely took any time at all. Before long the world was full of trilobites and anenomes, then fish, ferns, pterodactyls, tyrannosaurs, bees, whales, cacti, kangaroos, not to mention us.

Though this transition is known to have happened some two dozen times throughout history in plants, animals, algae and other life forms, scientists still question how and why it occurred.

“It really is a fundamental question,” said Hanschen, a PhD student at the University of Arizona at Tucson. “What is the basis of multi-cellularity and when did it evolve?”

Hanschen and his colleagues believe the answer might be hiding in our DNA. Specifically, they report in the journal Nature Communications, in a gene known as RB, which seems to be responsible for turning single-celled creatures into cooperative multicellular groups.

“Rather than hundreds of thousands of changes,” Hanschen’s co-author Brad Olson said. “There’s actually a regulator of gene expression that’s change”

But RB’s significance goes far beyond the academic. In humans (and pretty much everything else), it regulates the cell cycle – how cells grow and divide during their life spans. Problems with the gene are a known cause of cancer.

“If we understand the process by which cells cooperate for multicellular life, maybe it will tell us something about why cancer occurs at all,” said another co-author, Pierre Durand of the University of Witwatersrand in Johannesburg.

Hanschen, Olson and Durand are part of an international coalition of biologists studying the genomes of an unusual but ubiquitous family of green algae known as the Volvocaceae. The simplest of these species are mere single-celled organisms, but larger members contain up to 50,000 cells of different types.

They’re an ideal lineage for studying the evolution of complex life, Olson said, because each incremental increase in complexity illustrates a step along the path toward larger, multicelled beings.

The volvocine species Gonium pectorale – whose genome was just sequenced for the first time as part of the study – is right smack in the middle of that path, so much so it’s pretty much in evolutionary purgatory between the two stages. The 16 identical cells that make up each G. pectorale individual are less mobile and self-sufficient than their single-celled relatives (Durand noted that the cells in the middle of the Gonium have limited exposure to the outside world, meaning that they rely on their fellows to get nutrients for them). But they also lack the specialization and sophistication that makes multicellular life so appealing.

And yet, something is holding the 16 cells together, compelling them to act as one. That something seems to be the RB gene. When Olson, who teaches evolutionary genomics at Kansas State University, removed the gene from a Gonium and put it in its unicellular relative, Chlamydomonas, the formerly single-celled organisms started clumping together to form colonies.

“I was so surprised I asked someone else in the lab to repeat the experiment for me,” he said.

His colleague got the same results.

Hanschen, who is the lead author of the paper, noted that RB genes were first identified decades ago. But they’re notoriously difficult to study because the cell cycle is so fundamental to life. If you try and switch off the gene that controls it, everything in the cell starts to fall apart, he said.

The incremental differences between the various volvocines are a perfect natural experiment in what happens when the RB gene is not expressed. Cancer, which can occur when something with the gene goes haywire, is a less ideal experiment.

“If you’re a multicellular organism, all of your cells are cooperating, behaving altruistically, working together for the benefit of the whole,” Durand said. “But when you have a cancerous event, like a tumor, those cells have adopted a selfish behavior again.” Without the RB gene to regulate the cell cycle, cells start to divide without concern for the other cells they share space with – a process that can often turn deadly.

Still, the cycle works more often than it doesn’t. In Durand’s view, the existence of multicellular organisms is the most fundamental form of cooperation that exists: two living things deciding they have a better shot at success if they stick together. Practically every life form larger than a bacterium owes a debt to that decision.

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