These fish stole an antifreeze gene from another fish and became natural GMOs

Millions of years before scientists created genetically engineered Atlantic salmon with genes from two other fish, nature created genetically engineered smelt with a herring gene, growing evidence shows.

And now the Canadian scientists who first came up with this controversial idea say they have an idea of ​​how nature could have done it.

New study by Queen’s University researchers Laurie Graham and Peter Davies finds ‘conclusive’ evidence for controversial idea that antifreeze gene that helps rainbow smelt survive in icy coastal waters Originally sourced from herring and was sort of stolen by smelt around 20 million years ago.

They offer in their new article in Trends in Genetics that this could have happened through a process quite similar to how genes are sometimes transferred from one species to another by scientists in the lab today.

Stealing genes from other species

Genes are normally passed from parents to offspring. But in recent decades, scientists have discovered that they can also ‘jump’ or be ‘stolen’ from one species to another outside of normal reproduction – a process called horizontal gene transfer or lateral gene transfer. .

This is something that occurs frequently among microbes such as bacteria – so frequently that Canadian scientist W. Ford Doolittle has suggested it might explain much of the history of life on Earth.

There has been recent evidence that this occurs in some more complex organisms. For example, aphids seem to have stole a fungus gene to make a plant pigment and seaweed seems to have colonized the earth 500 million years ago using a gene stolen from soil bacteria. More recently, scientists reported last week first known case of a gene transferred from a plant to an animal.

In more complex organisms such as fish and humans, certain virus-like DNA sequences called “transposable elements” or “transposons” are also known to pass from one species to another.

But the same had not been seen for the useful genes that code for things like proteins. This is because the genes of multicellular organisms can only be passed from generation to generation if they specifically enter reproductive cells such as eggs or sperm.

Davies is a professor and holder of the Canada Research Chair in Protein Engineering at Queen’s University. Graham is a research associate in his lab.

When the two men first realized over a decade ago that herring and smelt had to share their antifreeze protein via horizontal gene transfer, it was the first time anyone had suggested that a vertebrate – a complex animal with a backbone – had transferred such a gene. to another vertebrate. This made it quite controversial.

“We had a hard time finding a journal to write our first article,” Graham recalls. “The reviews weren’t exactly kind and there was a lot of doubt.”

It didn’t help that one high-level report on the horizontal transfer of genes in complex organisms at the time, from bacteria to humans, had been questioned by other scientists, who proposed other explanations for the genes shared between the two types of organisms.

Clues indicating a stolen gene

Graham originally looked at different types of antifreeze proteins, not only in fish, but also in insects, bacteria, plants, and small soil creatures called springtails.

Most of them appeared to come from a common ancestor, with a similar structure in closely related animals.

But that wasn’t the case for herring and smelt, which are so far apart that the last time they shared an ancestor was 250 million years ago, around the time the first dinosaurs appeared. .

“All of the other genes that we looked at in these two species, they tend to be quite different,” Graham said.

Meanwhile, she added, the closer cousins ​​lack the antifreeze protein that Atlantic herring, Pacific herring, and rainbow smelt share.

“We have other fish that are more closely related to these species that make completely different types of antifreeze protein. So it doesn’t really make sense on an evolutionary basis if everyone inherits their antifreeze protein from theirs. ancestors.”

Skeptics weren’t convinced, so researchers looked for more evidence. Closely related fish such as different types of smelt tend to have the same genes in the same order. And the researcher found it was – with the exception of the antifreeze gene, which was found between two genes that are normally side by side in another smelt.

“This is what you would expect when you have a gene that has simply been stuck in a genome by horizontal gene transfer.”

Then, recently, researchers learned that the Atlantic herring genome had been published in a public database.

They decided to take a closer look.

Do you remember those transposable elements that often jump between organisms? They can also be used as a fingerprint for a particular organization. Herrings have certain transposable elements stuck hundreds of times throughout their genome, including in and around their eight antifreeze genes.

When researchers looked at smelt’s unique antifreeze gene, three of these herring transposables were attached, Graham said. “So it was like a little tag to say, ‘Hey, I’m herring.’ These transposable elements were not found anywhere else in the smelt.

The researchers say this is conclusive evidence that the antifreeze gene moved between the two fish via horizontal gene transfer and that it went from herring to smelt and not the other way around.

How did the gene skip the species?

When the researchers’ previous papers were peer reviewed, one of the questions the reviewers had was how the gene could have moved between species, so they sought to formulate a hypothesis.

One possibility, they thought, was that it could be similar to techniques used in the laboratory to create genetically modified animals. One, called ‘sperm-mediated gene transfer’, involves mixing the sperm with the DNA you want to introduce and then using it to fertilize an egg.

“And we thought, ‘Well, couldn’t that also happen in nature?’ Graham recalled.

Fish and many other marine animals have external fertilization, where eggs and sperm – known as milt – are released into the water at the same time in massive amounts during spawning, and some of them get combine to produce offspring.

Graham noted that when herring spawn on Canada’s Atlantic and Pacific coasts, “you can actually see that the ocean is kind of stained white with all the milt that male herring release.”

The semen breaks down after a few hours, releasing DNA into the water. And the researchers proposed that in one of these events, the DNA of the herring ended up in rainbow smelt eggs or sperm.

Graham admits there is no way to prove it – “not unless you have a time machine.”

But if this is how the genes were transferred, it probably happened with other genes in fish as well, Davies suggested, and scientists should start looking for other examples.

The other implication is that genetically modified organisms, which have been characterized by activists as “Frankenfoods”, might not be so artificial.

“One of the lessons to be learned here is that this genetic modification actually occurs in nature,” Davies said. “Not very often – it’s probably quite rare – but maybe we shouldn’t be so alarmed about it. It’s actually more of a natural occurrence than we previously thought.”

What other scientists think

Garth Fletcher, professor emeritus and head of the Department of Ocean Sciences at Memorial University, is the co-inventor of Aquabounty’s genetically modified salmon (but not by sperm-mediated gene transfer) and has previously worked with Davies to compare antifreeze proteins in fish. He was not involved in the new study.

Fletcher doesn’t think the research will reassure opponents of GMOs.

He says it’s significant that the researchers have come to the point where they believe their evidence for horizontal gene transfer in this controversial case is so strong. He credited the new techniques of molecular genetics for making this possible.

“Twenty years ago you couldn’t have done this stuff.”

Luis Boto, scientific director of the evolutionary biology department of the National Museum of Natural Sciences in Madrid, was monitoring evidence of horizontal gene transfer in complex organisms, and said the new genetic tools will allow scientists to explore how common this is.

“This article opens the door to an important area of ​​research as the sequencing of new fish genomes will provide us with interesting results,” he added in an email, “and will allow us to better understand the ‘possible importance of horizontal gene transfer in animal evolution. “

He said evidence for horizontal gene transfer in vertebrates remains scarce, but the new article offers “significant support” in the event that this happens between herring and smelt.

Gane Ka-Shu Wong, professor of biology at the University of Alberta, is also convinced by the study and believes the way the gene went from herring to smelt is plausible.

Wong published a study a few years ago showing plants, which were confined to the oceans, stole a gene from soil bacteria to acquire the ability to colonize the land.

Although such horizontal gene transfer events seem rare in complex organisms, if they help the organism to survive, they could make a big difference, he said.

“I guess a lot of important evolutionary events may have been caused by some sort of horizontal gene transfer.”