by Francesca Tomasi
figures by Olivia Foster Rhoades
Argonaut. Idéfix. Flamenco. These words invoke movement: the ancient Greek Argonauts were a band of adventurous sailors famous for their epic quests. Meanwhile, Idéfix is the name of an adventure-loving dog in the French Astérix comic book series. And finally, flamenco conjures images of vivacious dancers. You would think the similarities between Greek mythology, French comic books, and Spanish dancers end there. Thanks to their common thread of movement and to the whimsical humor of geneticists, these words get to share something else in common: all three are also names given to some so-called transposable elements, or transposons. Transposons copy (or cut) and paste themselves in different parts of your genetic material, and in so doing are able to cause real-time changes in your genetic makeup. Most of the time, these transposons go unnoticed. But over billions of years, they have played an integral role in evolution. It’s time we give transposons the recognition they deserve: without them, we simply would not be here.
A very brief introduction to genetics
The word “genome” is used to describe the complete set of DNA, or genetic material, in our cells. Our genome is like a very organized and detailed book that describes how to make a human being. The human genome consists of about thousands of genes, which are analogous to words that come together to make sentences that describe you. Genes carry the blueprints for everything that makes up your body and governs life processes. Just like the letters of the alphabet that are strung together to make words, your DNA is strung together to make up your genes. The thousands of genes in your genome are coordinated to build you, one of nature’s most intricate biological factories.
A brief introduction to transposons
The idea that our genome is as immutable as a published book, as logical as it sounds, is not actually entirely correct. Although the 20,000 genes that are essential to life are always found in the same relative order in healthy humans, it turns out—thanks to the groundbreaking research of Barbara McClintock in the mid-1900s—that we also have some rogue genes hanging out in our genome. These “jumping genes” are the transposons I mentioned above, and they can hop around in our genetic material, inserting themselves pretty much anywhere (Figure 1). A transposon lurking in your genome is like a random word inserted somewhere in the middle of a sentence. It can either change the meaning of the sentence—subsequently causing disruptions in your bodily functions, as we will discuss later—or it can be innocuous. In fact, nearly 46% of your DNA is made up of transposons that at one point or another went rogue without actually causing any harm.
Transposons in evolution
Mother Nature isn’t stupid: these rogue genes—which are like random words—cannot continue to jump around, or they will eventually paste themselves in so many places that our genome “book” would just stop making any sense. For millions of years, transposons enjoyed plenty of travel around our genome. They inserted themselves throughout our evolving DNA for as long as they could before these changes started to make the host human less suited for survival in a given environment. When their random insertion provided some sort of life advantage—increased ability to absorb certain nutrients, for instance—or took place with no negative effect, the resulting modifications to the genome were passed on to future generations. Any insertions that caused death or illness, meanwhile, were a lot less likely to make it past a single generation. As such, over millions and millions of years of trial and error, transposons gradually integrated themselves in increasing numbers throughout our genomes. Eventually, their ability to move without negative consequence likely became, for the most part, saturated. And as a result, over 99% of the transposons in the human genome lost their ability to move. But we still have some active transposable elements within us: sometimes they can wreak havoc and cause disease.
Transposons in disease
LINE-1 (for “long interspersed element 1”) is the name of a very active transposon in the human body (Figure 2). As with most transposons, LINE-1 migrations are generally harmless. In fact, LINE-1 has inserted itself around our genomes so many times over the course of human evolution that it alone makes up as much as 18% of our genome!
Sometimes, however, LINE-1 lands in APC, which is an essential gene in our body. This means that disrupting this gene negatively affects our health. LINE-1 insertions have been linked to different kinds of cancer, including colon cancer. Scientists have even found abnormally high levels of LINE-1 in general to be a hallmark for multiple types of cancers (Figure 2). Similarly, insertion of LINE-1 into a gene responsible for blood clotting can lead to the bleeding disorder hemophilia A. Going back to our book analogy, if a gene like APC is one word like “cat” and the transposon is another word like “dog,” sticking a transposon into a gene—“cdogat”—-makes the original word lose its meaning.
Altogether, transposons have been with us through the good, the bad, and the ugly. We’ve seen these genes hop around unnoticed in our genomes for millions of years, every so often helping us survive, or causing disease. We’ve always been a naturally adventurous and dynamic species. For thousands of years, humans were constantly on the move, discovering new places and ways to live. Now, our adventurous spirits have taken us all over the world. We grow up reading stories and watching movies about adventure, whether the main characters are ancient Greeks or talented dancers. Wanderlust is, colloquially, in our DNA. Now, thanks to modern science, we also know it’s literally in our DNA.
Francesca Tomasi is a second year PhD student in Eric Rubin’s lab, studying new drug targets to treat tuberculosis.
Olivia Foster Rhoades is a fourth-year PhD student in the Biological and Biomedical SCiences program at Harvard & is pursuing a concentration in STS at the Harvard Kennedy School. You can find her on Twitter as @OKFoster
- To learn more about how transposons have played a role in our own evolution, check out this SITN piece
- To learn more about why transposons are called “selfish” genes, and the different ways in which they work, see this article in Science
- For a more in-depth history of transposons and their discovery, see this review in Genetics
- To learn more about the role of transposons and disease, check out this article from the University of Arizona