How Virus-like ‘Jumping Genes’ Became Our Partners in Evolution

Half of our genome is made of transposons — snips of DNA that can move and copy themselves. But they’re more than parasites or genetic junk. Introduction You might imagine that the DNA in your cells has a simple history. Even though it’s been recombined in every generation through sex and gained the occasional mutation, on the whole the genome has been stable and has been passed down reliably from your ancestors. But that’s not the entire story. Nearly half of your genome is a wild drama: mobile, repetitive, disruptive, even viral. This half is the result of genetic material that can clip itself out of the DNA sequence, float off, and re-root somewhere else. These sequences can multiply and expand, inflating the genome from within. They can hop into the middle of another sequence and break it. They can also be fertile soil for new adaptations to grow. These unruly genetic fragments are known as transposable elements, or transposons for short. Often called jumping genes for their ability to relocate in a genome, they may seem pathological — indeed, many have viral origins — or perhaps little more than junk. But transposons are increasingly understood to be a key feature of many genetic tool kits. Their connections to the evolution of everything from moths to wombs, and even to the fundamental biological processes that turn genes off and on, suggest that the relationship between host genome and transposon is best understood as a deep coevolutionary entanglement. The Copy-Paste Parasites The first hints of transposons’ existence were uncovered more than 80 years ago by the geneticist Barbara McClintock while she was studying color variation in corn kernels at the Cold Spring Harbor Laboratory in New York. She worked with a corn strain whose kernels were typically solid purple, but some were speckled, with purple pigment spattering a yellow base. She hoped to explain how genes produced this color variation. McClintock’s explanation would challenge geneticists’ understanding of how the genome works. She discovered genetic elements that could move: They could excise themselves from one location and insert themselves into another on the same chromosome or a different one. Sometimes, these genetic acrobats would jump into the middle of a purple pigment gene and interfere with its function, producing a speckled cell. If it jumped out again, the pigment gene would be restored, making a purple cell. Barbara McClintock’s description of mobile genetic sequences in 1944 was initially treated with skepticism. She was awarded a Nobel Prize in 1983. Smithsonian Institution Science Service; Restored by Adam Cuerden McClintock called these mobile genes “controlling elements” for their dominion over the expression of the color-producing genes; today we call them transposons for their ability to transpose themselves, or change positions, within a genome. Three decades later, in 1983, McClintock was awarded a Nobel Prize for her discovery, which showed that genes are not fixed in place. Since then, researchers have uncovered transposons in organisms across the tree of life and described a whole taxonomy of subtypes that cluster into two main groups. The transposons McClintock discovered are DNA transposons, so called because they travel as a DNA molecule. Transposons in this class jump by means of “cut and paste.” Enzymes called transposases bind to the ends of the DNA transposon and splice it free. The liberated bundle then touches down somewhere else in the genome, where native DNA repair processes paste it in. A second class of transposons, known as retrotransposons, aren’t cut directly out of the genome. Instead, the DNA sequence is copied into RNA, a molecular strand that is flexible and mobile by nature. Liberated from the genome, the sequence in the RNA copy is then reverse-transcribed into DNA at a different location. By copying themselves instead of cutting, retrotransposons can easily flood a genome with many iterations of themselves. Over time, this has led retrotransposons to make up large proportions of a host genome in some cases; for example, nearly half of the human genome is retrotransposons. McClintock’s curiosity about which genes create purple or yellow kernels on the same cob of multicolored corn led to her uncovering a fundamental mechanism of genetics. Science History Images Eerily, many retrotransposons are related to viruses; biologists debate which came first. These viruses, known as retroviruses, insert a DNA copy of their RNA sequence into the host cell’s genome, hijacking the cell’s resources to reproduce themselves. The most widely known example is HIV, which invades the genomes of infection-fighting white blood cells. If they don’t kill their host, retroviruses’ genetic legacy can be left behind in the host genome afterward, like splinters lodged in a finger. This viral scar tissue can accumulate over millions of years: In humans, these viral ghosts make up an estimated 8% of the total genome. That means we are in no small part made of virus. The same features that allow DNA transposons and retrotransposons to move within a genome also predispose them to moving between genomes. By hitchhiking on a passing virus, transposons can defy species boundaries and land in a totally new evolutionary setting. “Virtually all of the [transposon types] we know can apparently go from species to species,” said Cedric Feschotte, a geneticist at Cornell University. Initially, these “horizontally transferred” transposons were thought to be a rare exception to normal biology. But by now, thousands of examples have been reported, Feschotte said, in species that run the gamut from fungal pathogens to snakes to cows. In 2020, researchers described nearly 1,000 independent horizontal transfer events in 307 vertebrate genomes, predominantly in fish. Given their self-replicating, virus-like behavior, it’d be understandable to consider transposons as something between benign bloat and selfish parasite. But researchers are increasingly finding that, as in the case of McClintock’s corn kernels, they can be a source of meaningful evolutionary material. Invasive Adaptation Around 200 years ago, the peppered moths of England were readily identifiable by their black-speckled white wings, which camouflaged well with pale tree bark. But after the Industrial Revolution, when pollution from coal-powered factories darkened the trees, black wings came to dominate the population. Evolutionary biologists later explained that in the new, sootier environment, white moths were easily spotted by predatory birds, while black moths blended in with the darkened bark. The white moths had lost their survival advantage, and black moths survived better and reproduced. Life marched on. This story about the dark-winged peppered moths is now considered a textbook example of natural selection. However, it wasn’t until 2016 that researchers uncovered the genetic mechanism behind the wardrobe change. By sequencing hundreds of peppered moth genomes, the geneticists found a significant and consistent difference in a gene called cortex involved in wing development. A transposon, absent in the white-winged moths, had been inserted into the beginning of this gene in nearly all the black moths and had led, through an unknown mechanism, to the production of dark-colored wings. The black morph of the peppered moth evolved when a transposon inserted itself into a gene that controls wing pattern. Ian Redding The authors estimated that this transposition occurred in 1819 — after the rise in pollution levels had started to alter the moth’s habitat. “This is completely changing how we see rapid adaptation,” said Pierre Baduel, a geneticist at the French National Center for Scientific Research in Paris. It is typically thought that generating new traits takes long periods of evolutionary time. In this case, a transposon created a new trait that was immediately selected for. These types of insertions may happen frequently. But to be passed on to the next generation, they need to occur in the reproductive cells. Any insertions that have large, immediate, and potentially negative effects on an organism are usually rapidly weeded out by natural selection. “The genome is just constantly bombarded by gene insertion, and then most of them are removed,” Baduel said. “If the environment has changed and suddenly they become adaptive, then they stick.” Sometimes, instead of changing an existing gene, a transposon in a new context can be co-opted over time to generate something new. For instance, a transposon fused in the right location can, by chance, create a novel protein that goes on to regulate other genes spread throughout the genome. This process of tweaking genes to establish new traits is thought to have catalyzed evolutionary novelty in animals. Transposable elements are linked to the evolution of animal eyes as well as the adaptive immune system in jawed vertebrates. The domestication of transposons for new purposes has also been implicated in the evolution of the placenta — a defining feature of nearly all mammals. That means that a transposon is partly responsible for the months-long process of development in utero that’s typical for our lineage, humans included. Even when the effects are more subtle, the relationship between genome and transposon seems to sometimes go deeper than that of a host adapting to an invading, self-interested genetic force. In many cases, it could be considered more of a coevolutionary arrangement, Feschotte said. Some products made by transposons may do the same jobs as native proteins, and over time, the host genome may become dependent on the transposon and its products, a situation he compared to an addiction. This drive for coexistence may undergird fundamental aspects of how genomes regulate themselves. The disruptive nature of transposons may have required organisms to evolve new methods of shutting off their activity. Epigenetic control — the means by which an organism can dial the expression of its genetic repertoire up or down, or shut off the expression of some genes entirely — may have evolved first to bring transposons to heel. “One of the models is that relatively simple organisms evolved epigenetic silencing to silence their transposons,” said Susan Wessler, a geneticist emerita at the University of California, Riverside and vice president of the National Academy of Sciences. Under this theory, organisms figured out how to turn genes off to get these unruly genetic parasites under control. Then evolutionary processes repurposed those controls to turn all sorts of genes off, leading to regulatory processes that, for example, produce dozens of cell types from the same genome. This coevolutionary perspective is a more neutral take on the relationship between transposon and host genome, Feschotte said, compared to how they’ve been viewed in the recent past, as “selfish,” “parasitic,” or “junk” DNA. Now, the emerging understanding that transposons are intimately interwoven within the regulatory workings of the host genome is rehabilitating their reputation as critical sources of evolutionary innovation. “We are all influenced by the terms that we use,” Feschotte said. “[Transposons] are not just passengers. They’ve been coevolving with organisms from the beginning.” The Quanta Newsletter Get highlights of the most important news delivered to your email inbox Also in Biology Comment on this article Next article Mathematicians Build Long-Awaited Graph Sandwich