Recent research into transposons within DNA dark matter may produce new biomarkers for clinical laboratory testing and diagnostics

There’s been another interesting development in the study of genetic “dark matter” which may give rise to new biomarkers for clinical laboratory diagnostics and testing. This is worth noting, because biological dark matter has long been considered non-critical and immaterial to the human organism or human evolution. Researchers often refer to it as junk DNA.

However, newly-released research suggests that transposons (aka, transposable elements) contained within our genetic dark matter may play a “critical role in mammalian development,” according to a UC Berkeley news release. Transposons, the release notes, are “viral elements [that] have invaded mammalian genomes for millions of years and currently make up nearly half the DNA in the genomes of all living mammals.”

The study, led by researchers at the University of California, Berkeley, and Washington University in St. Louis, found at least one family of transposons that affected the viability of test mice. They believe the transposon could play a similar role in all mammals—including humans.

The researchers published their study in the journal Cell, titled, “A Mouse-Specific Retrotransposon Drives a Conserved Cdk2ap1 Isoform Essential for Development.”

Lin He, PhD

Molecular biologist Lin He, PhD (above), led the study conducted at the University of California, Berkeley, and Washington University in St. Louis, which found that bits of DNA once considered “junk” may actually perform important functions, such as ensuring fertility. These findings may one day confirm new biomarkers for clinical laboratory testing. (Photo copyright: MacArthur Foundation.)

How Removal of a Transposon Led to Death

The researchers found that the function of one type of transposon affected whether a mouse fetus could form properly and survive birth. The transposon “regulates the proliferation of cells in the early fertilized embryo and the timing of implantation in the mother’s uterus,” the news release notes.

To perform the research, the scientists removed a specific transposon that controls the proliferation of cells in the early fertilization of an embryo from the mice. After extracting that transposon, half of the mouse pups died before birth.

The researchers then looked at other mammalian species—including humans—and “found virus-derived regulatory elements linked to cell proliferation and timing of embryo implantation, suggesting that ancient viral DNA has been domesticated independently to play a crucial role in early embryonic development in all mammals,” UC Berkeley noted.

The researchers suggest that some of our dark matter DNA has an important function in our embryonic maturation and survival.

“The mouse and humans share 99% of their protein coding genes in their genomes—we are very similar with each other,” said molecular biologist and senior author of the study Lin He, PhD, Associate Professor, Department of Molecular and Cell Biology, UC Berkeley, in the news release.

“So, what constitutes the differences between mice and humans? One of the major differences is gene regulation—mice and humans have the same genes, but they can be regulated differently. Transposons have the capacity to generate a lot of gene regulatory diversity and could help us to understand species-specific differences in the world.”

“The real significance of this story is it tells us how evolution works in the most unexpected manner possible,” said geneticist and study co-author Ting Wang, PhD, Sanford and Karen Loewentheil Distinguished Professor of Medicine, Department of Genetics, Washington University School of Medicine, in the UC Berkeley news release.

“Transposons were long considered useless genetic material, but they make up such a big portion of the mammalian genome. A lot of interesting studies illustrate that transposons are a driving force of human genome evolution. Yet, this is the first example that I know of where deletion of a piece of junk DNA leads to a lethal phenotype, demonstrating that the function of specific transposons can be essential,” he added.

Their research could have implications for human fertility as many miscarriages in humans are due to undiagnosed conditions or have no apparent genetic component.

“If 50% of our genome is non-coding or repetitive—this dark matter—it is very tempting to ask the question whether or not human reproduction and the causes of human infertility can be explained by junk DNA sequences,” he said.

Other Studies Involving So-called ‘Junk DNA’

In “Researchers Discover Links Between Non-Coding DNA and Cancer Growth That Could Lead to New Clinical Laboratory Biomarkers for Cancer and Other Chronic Diseases,” Dark Daily reported on studies conducted at the Ontario Institute for Cancer Research (OICR) and the Cancer Research UK in England which also concluded that portions of mammalian DNA previously considered “junk” may in fact be performing critical functions, such as, for example, preventing cancer.

Thus, the UC Berkeley/Washington University study is building on prior research demonstrating that dark matter DNA may not be “junk” after all. More specifically, transposons may eventually have value as biomarkers for clinical laboratory tests and diagnostics.

Of course, additional research and studies are needed to validate these findings and provide greater knowledge about the function of specific transposons. But it’s an intriguing development that’s worth following.

—JP Schlingman

Related Information:

So-called Junk DNA Plays Critical Role in Mammalian Development

Transposons: The Jumping Genes

A Mouse-specific Retrotransposon Drives a Conserved Cdk2ap1 Isoform Essential for Development

Efficient Mouse Genome Engineering by CRISPR-EZ Technology

Researchers Discover Links Between Non-Coding DNA and Cancer Growth That Could Lead to New Clinical Laboratory Biomarkers for Cancer and Other Chronic Diseases