The prey is constantly in flight. Jumping from one part of its habitat to another, one step ahead of its predator. Finally, accidentally, it stumbles into a hiding place, where it finds others of its ilk. The prey joins its fellows in a tight huddle, out of reach of its predator. Safe at last.
This prey, though, is not a zebra fleeing across the Serengeti from a lion, a deer leaping through the forest steps ahead of a wolf, or a fish, darting to a clump of its fellows in the shadow of a rock. It is a gene—a clump of DNA called transposable element, transposon, or sometimes a “jumping gene.” These sequences of DNA move through the genome. In a way, they are prey, constantly on the move. They have predators—the protective cellular machinery which finds and suppresses them. It can stop them from creating RNA or proteins or moving around the genome.
In this way, each cell’s genome can be thought of as an ecosystem, like a coral reef or savanna. Scientists have been using the metaphor of an “ecosystem” to make such a tiny inaccessible world a bit more comprehensible—to themselves as well as non-scientists.
But some researchers want to take the idea beyond simple metaphor. With funding from the John Templeton Foundation, evolutionary biologist T. Ryan Gregory, philosopher of science Stephan Linquist, and their colleagues at the University of Guelph in Canada want to apply the methods and theories of ecology to the genome—asking genetic questions through an ecosystem lens.
The project could offer new ways to study how genomes change over time. But it also opens up bigger questions. If the genome is an ecosystem, are the transposable elements in it independent agents? Are they pursuing goals of their own?
And if they are, how should we think about the genomes–like those in humans–that host thousands of these elements?
Jump gene, jump
The story of transposable elements has until now been the story of metaphors. After all, if scientists thought of DNA as a blueprint, a plan for a house that is a cell, then the genes within that blueprint, the walls and floors and doors, should remain in the same place. When Barbara McClintock described the first jumping genes in corn in 1950, the blueprint model began to seem a bit odd. The walls and windows could move.
Transposons are “really just any element that can be moved around the genome,” says Richard Hunter, who studies the neurobiology of stress at the University of Massachusetts in Boston. Some, called DNA transposons, really are jumping—or as much as anything without legs can be said to leap. Enzymes called transposases cut them nearly out of the genome at either end, and they land and insert themselves somewhere else, a cut-and-paste method. Others, called retrotransposons, are copy-and-paste. They are transcribed into RNA just like a regular gene, and then the cell pops bases onto the empty side of the RNA, producing a DNA strand copy, which is pasted into the genome.
Because of their ability to copy themselves and pop around the genome, transposable elements account for a lot of genome size. Around 45 percent of the human genome is transposable elements.
But in other species, it’s far, far more, says Susan Wessler, a molecular geneticist at the University of California, Riverside. “Take the rice genome, which is very small, it’s 350 megabase pairs,” she says. Rice and maize are both grasses, and though they split about 60 million years ago, the maize genome is now a full six times larger than rice.
“The reason the maize genome is six times bigger than the rice genome is because there are transposons. That’s it, basically,” Wessler explains. “And so you’ll have two genes in rice that are pretty close together, and in maize they could be 100,000 basepairs apart. And between them are these islands of transposons.”
One scientist’s “junk” is another’s treasure
Articles about transposable elements often begin with another metaphor: That transposable elements used to be thought of as “junk DNA.” Gregory loathes this characterization. Yes, “junk DNA” was a term, he notes, but that doesn’t mean people thought it was useless. “The term was coined by Japanese American geneticist Susumu Ohno in the early 1970s,” Gregory explains. “He was using it to refer to a very specific kind of DNA in the genome.” Ohno was talking about genes that had been copied, but then one copy got mutated and stopped working. “So it was junk, in the sense that it was something that was functional and had lost its coding function.”
In a way, notes Wessler, that does mean it’s junk, genes that lost coding function and are now in the genome, gathering molecular dust. “We just can’t get rid of it.” But a layperson’s “junk” is a scientist’s potential treasure. “We don’t know what it does. Let’s put it this way, put it that way,” Wessler says. “The only way to say it’s useless is really to eliminate a lot of it and see if the organism functions the same.”
DNA after all doesn’t have to produce a protein to have a function. “The default view was that it was functional in some way,” Gregory says. “And even Ohno said [junk] doesn’t necessarily mean non-functional. It means it originated through this mechanism.”
If jumping genes aren’t junk, what is their utility? “We know that at least in single cell organisms, replication pressures are a significant concern,” Hunter says. It takes work to copy a genome when a cell reproduces, so getting rid of real junk is a high priority. “And why would we have 50 to 90 percent of our genome [be] stuff that doesn’t do anything?”
Some thought of them as spacers, the packing peanuts of the genome, stopping genes from running into each other.
But it quickly became apparent that wasn’t true. Genes frequently overlap each other. “What evidence was there that if genes bump into each other, they explode or break?” Hunter asks. “We know now that genes are running on overlapping strands and stuff like that.”
McClintock suggested the elements could have regulatory functions over other genes. Some of them do appear to do things that benefit the cells in which they reside. Others seem to be leftovers of viruses—incorporated into the genome and now replicating themselves over and over, potentially emerging in times of stress.
Transposons can also burst out periodically into massive numbers of copies, spattering everywhere in the genome. “I do think they’re beneficial,” Wessler says. When transposable elements burst forth, “they allow the genome to evolve much more rapidly than by the usual processes of base pair mutations and things like that.” Their cuts or copy and pastes “allow the genome to rearrange, which is now known to be a very important type of mutation in terms of affecting traits.”
But change is not always positive, or even neutral. When they bounce into the middle of important coding genes, or genes that control other genes, the results can be disastrous. Cells even have specialized machinery that hunts down transposons, shutting down their activity.
What if transposable elements didn’t have to be “good” for the genome? What if these elements were in the genome for reasons of their own? Some could be parasites—replicating over and over inside their host genome and causing trouble at best. Others could exist tamely inside the genome, causing no trouble. Still others might be mutualists—offering beneficial genes to their hosts. These are metaphors for how transposons could behave. And they’re metaphors that Gregory and his colleagues want to take to the next level—studying the genome as though it were an ecosystem unto itself.
From metaphor to ecological model
If this seems like a bit much for a stretch of simple genetic code, it depends on how you think about ecosystems and the agents acting within them. Jumping genes appear to act in ways that preserve their existence. They copy themselves over and over—keeping themselves present. Their behavior is flexible—some jump more in germ cells, others under stress. They can sometimes burst out in efflorescences of copies, a bumper crop of genes.
The ecosystem idea could also extend further. Transposons often end up clumped together in particular areas of the genome—an ecological niche. These clumps are hidden in the safety of sections of rarely used code, or squished up next to genes too important to suppress. Cellular mechanisms that suppress those transposable elements could be thought of as predators, pouncing on any elements caught in the open.
Gregory, Linquist and their colleagues want to use tools developed in ecology to explore beyond the language of metaphor. Methods like ecological sampling—picking a strip of genetic “habitat” and seeing what is present—as well as models for predator-prey dynamics or parasitism could help them understand what is happening inside the nucleus of each cell. “What we’re saying is take it as if it weren’t just a convenient metaphor, but actually is what’s going on,” Gregory says.
It wouldn’t be the first time that transposable elements have been thought of as having some kind of independent agency. Scientists have already considered transposable elements as goal directed—fundamentally selfish, as Richard Dawkins wrote in his 1976 book The Selfish Gene. “A selfish genetic element is one that serves its own goals, but not the goals of the organism to which it belongs,” explains Manus Patten, an evolutionary biologist at Georgetown University in Washington, DC.
A transposon with the simple goal of replicating itself could then be a distinct agent, but it’s not acting alone. It’s within the genome, in a complex habitat. Patten agrees that it makes sense to study transposable elements with their ecology in mind. “If you take this ecosystem approach, given everything we know about how ecosystems work, there might be novel insights you can gain about transposable elements, which, if you just tried to think about transposable elements in their own right, you might miss, you might overlook,” he says.
Transposable ecosystems
Gregory, Linquist, and the collaborators hope to make genetic ecology yet another way to probe what transposable elements are, what they do, and why they are in the genome at all. “Ecology is a very rich theoretical field that has a long history of integrating data and theory, here is a new kind of data that could be approached with it,” says Arvid Ågren, an evolutionary biologist at the Cleveland Clinic Lerner College of Medicine at Case Western Reserve University in Ohio. “And I think the only way to find out if it’s a productive way of thinking is by doing it.”
But every way of thinking, about genomes or ecologies, brings assumptions with it. Assumptions about what counts as “useful” or “successful.” Those assumptions form the parameters of any model—the numbers that scientists think are important to include. And scientists might have different definitions of success.
Perhaps success is movement. Perhaps it’s low-level persistence.
“The ones that can attain a high-copy number I call successful, because they’ve been able to do that without killing their host,” Wessler says. They persist not because of what they do to the host – but because of what they don’t. “There are elements present in the maze genome, like 10,000 copies. They never caused a single mutation. And that’s the basis for their success.” Wessler notes that in some cases, scientists may not yet know enough to make a model, ecological or otherwise. “It is possible that you can model that kind of stuff, but I don’t think we know enough about very active elements to be able to devise the parameters for that model.”
No metaphor or model will be perfect. DNA isn’t really a blueprint, and it’s never been full of junk. The value of metaphors is in how they make scientists think about the things they study. “It’s very hard to do biology without metaphors,” Ågren notes. Each offers a way of thinking and grappling with structures too tiny to see, and interactions completely foreign to our experience. “I find it…a very helpful way to make sense of the world, and we need all the help we can get,” he says.
The genome might not be a forest, full of deer and wolves and trees, but thinking about it that way—in terms of the interactions between species in a particular place—could offer new insights into how the chemical interactions of DNA work. “I’m keen to see what they will find with it.”
Bethany Brookshire is an award-winning science journalist and author of the book, Pests: How Humans Create Animal Villains. Her work has appeared in Scientific American, The New York Times, The Washington Post, The Atlantic, and other outlets.
