'Evolution brings different solutions to the same challenge'

Israeli scientists say they’ve discovered a unique immune system in sea anemones

Evolutionary split 600 million years ago upends long-held scientific belief that all animals share one ancestral antiviral system; study can help save endangered coral reefs

When the sea anemone split from the lineage leading to humans about 600 million years ago, this ancient marine animal’s immune system also developed its own way of fighting viruses, Israeli researchers found in a groundbreaking study.

In peer-reviewed research, scientists from the Hebrew University of Jerusalem, in collaboration with the University of North Carolina at Charlotte, discovered a brand-new protein that has helped the immune system of Nematostella vectensis, the starlet sea anemone, defend against viral attacks for all these years.

“We found a CARD protein — a structural building block we named CARDIB — that prevents unnecessary immune response by binding to the sensor for viruses,” lead author Ton Sharoni told The Times of Israel.

The discovery upends a long-held scientific assumption that the immune systems of all animals, from anemones to humans, descend from a single ancestral antiviral system and fight viruses in the same way.

“Evolution arrived at different molecular solutions to meet the same biological challenge,” he said.

If the moniker brings to mind famous rapper Cardi B, that’s no coincidence — although the protein is pronounced “cardib.”

“That was simply a fun bonus that made the name a little more memorable,” Sharoni said.

“Gene names are often technical and not always easy to remember,” he said. “In this case, we were able to create an acronym, CARDIB, for CARD Inhibitor Binding Protein, that reflects the protein’s function.”

Insights that could help save coral reefs

Sea anemones, along with corals and jellyfish, are cnidarians, a large group of aquatic invertebrates. Because anemones are closely related to corals, the researchers said these immune system findings could lead to new ways to help stem the threat to coral reefs.

“About 30 percent of life in the sea depends on corals, and when corals die, all the fish and the invertebrates depending on them also die,” Prof. Yehu Moran, who supervised the research, told The Times of Israel.

“Since viruses very likely play a part in coral’s deterioration, understanding their immune system is crucial,” Moran said. “By studying the sea anemones’ anti-viral system, you can work to save the corals and save life in the seas.”

The findings were published in Nature Ecology & Evolution.

No CARDIB, no protection against viruses

Since 2020, with a €2 million ($2.3 million) grant from the European Research Council, Sharoni set out to uncover how the sea anemone’s immune system functions together with Moran, who is an evolutionary biologist at Jerusalem’s Hebrew University,

At first, they hypothesized that the antiviral protein now known as CARDIB had a structure similar to that of MAVS, which is found in humans and other primates.

Using CRISPR, a gene-editing technology, the scientists deleted the CARDIB gene from a group of starlet sea anemones in their lab.

“The first surprise was that we were even able to generate these kinds of animals, and that they reproduced and survived,” Sharoni said.

“A few years into the project,” Moran said, “we discovered that the way CARDIB functioned was the complete opposite of MAVS. That was the biggest surprise.”

Moran said that in humans, MAVS is an “on” switch that immediately activates the immune system when a virus is detected.

However, CARDIB functions like an “off” switch that constantly keeps the immune system in the sea anemone from turning on.

“Think of it like Mel Gibson in ‘Braveheart’ holding back his soldiers,” Sharoni said.

To test the findings in the wild, the researchers brought the genetically modified sea anemones into outdoor marine tanks in South Carolina.

There, in the starlet sea anemone’s native habitat, they were exposed to nature’s diverse mix of threatening viruses.

Within a few days, the anemones lacking CARDIB became more vulnerable to infection.

“This protein plays a crucial role in helping these animals cope with the viral challenges they face in nature,” Moran said.

An animal’s immune system has to evolve faster than viruses in its struggle to stay alive, Moran said.

“It’s part of what’s known as ‘the evolutionary arms race’ between viruses and cells,” Moran explained. “There is not a single cell on Earth that doesn’t have a virus that has somehow evolved to infect it.”

Understanding how ancient animals fought viruses shows that “evolution has organized defenses in fundamentally different ways,” Moran said.

However, he said, “when lab experiments are done almost exclusively on humans and mice, the evolutionary innovations of ancient animals such as sea anemones remain invisible.”

“This study shows that despite its structural similarity to the vertebrate antiviral protein MAVS, CARDIB operates through a distinct mechanism,” Prof. Uri Frank of the University of Galway told The Times of Israel.

Frank was not involved in the research.

He said that this discovery “demonstrates that some aspects of antiviral immunity emerged independently in distantly related animals through convergent evolution rather than from a shared ancestral pathway.”

“This work provides new insights into the arms race between pathogens and their hosts,” Frank said, “and shows that evolution can come up with different solutions to solve similar problems in different animals.”

Because evolution has had “hundreds of millions of years to solve the problem of viral infections,” he said, “by studying some of the earliest animals on Earth, we can discover immune strategies that are very different from our own.”

This knowledge may also help further understanding of how corals and their relatives respond to viral infections and environmental stress, Sharoni said.

“In the long term, this could contribute to future conservation efforts,” he said.