Scientists Find Secret Code in Human DNA

One person’s junk is another’s treasure.

An international team of scientists have found that strings of “junk” DNA in the human genome that were previously written off as having no useful function are actually pretty important after all.

The work, published as a study in the journal Science Advances, focuses on transposable elements, a class of DNA sequences that can “jump,” via a biological copy-and-paste mechanism, to different locations in a genome. These “jumping genes” take up nearly 50 percent of human DNA; in other organisms, the proportion is even higher.

What the researchers from Japan, China, Canada, and the US found is that a particular family of these TEs, called MER11, can strongly influence gene expression and act like “genetic switches” — without actually changing the underlying DNA.

“Our genome was sequenced long ago, but the function of many of its parts remain unknown,” study coauthor Fumitaka Inoue from Kyoto University said in a statement about the work. 

MER11 sequences are what’s known as long terminal repeat (LTR) retrotransposons. Spookily, these are believed to have originated from an endogenous retrovirus (ERV) that infected a simian ancestor tens of millions of years ago, hijacking the DNA of the cells it invaded to produce copies of its genetic makeup that have never gone away, but have largely remained inert. Per the researchers, at least eight percent of the human genome comes from these retroviruses.

That, plus all the other TEs littering our genome, makes for a lot of puzzling clutter for human scientists to sift through. The authors argue that the current methods for classifying and annotating TEs are inaccurate, leading to DNA sequences being overlooked as genetic junk. This inspired them to test their own classification system. 

“The proper classification and annotation of LTR instances is critical to understanding their evolution, co-option and potential impact on the host,” the authors wrote in the study.

The researchers’ system classified MER11 sequences based on their evolutionary relationships and how well they were preserved in primate genomes, according to the researchers’ statement. Then, they divided MER11 into four separate subfamilies, MER11_G1 through G4, based on their age.

This allowed the team to compare the MER11 subfamilies to what are known as epigenetic marks: chemicals that can affect how important proteins function, and as a consequence affect gene activity. Crucially, epigenetic marks don’t have to physically alter a cell’s DNA to modify a cell’s behavior, such as silencing a gene that should be expressed. Accurately tying the MER11 subfamilies to the markers is a key step to revealing the extent of their impact on gene expression.

With that as a springboard, the team tested some 7,000 MER11 sequences from humans and primates, measured how much each one affected gene activity, and found that the youngest MER11 subfamily, G4, had a strong ability to influence gene expression — namely, by bearing its own DNA “motifs” that attract proteins called transcription factors that regulate what genes are switched on and off.

“Young MER11_G4 binds to a distinct set of transcription factors, indicating that this group gained different regulatory functions through sequence changes and contributes to speciation,” lead author Xun Chen from the Chinese Academy of Sciences said in the statement.

The implications are fascinating. Though these strands of DNA may have started as “junk,” they have gradually insinuated their way to playing a role in gene regulation today — suggesting a vast portion of unknown evolutionary history that we’re only scratching the surface of.

“Transposable elements are thought to play important roles in genome evolution, and their significance is expected to become clearer as research continues to advance,” Inoue said.

More on genetics: Elon Musk Using Eugenics Startup to Inspect DNA of Potential Babies for Intelligence