Genes from Ancient Viruses in Human DNA Linked to Development of Cancer

An eye-opening new study from genetic scientists at the University of Colorado-Boulder has discovered something surprising and alarming about some mysterious foreign DNA found in the human genome.

This DNA was introduced into the genomes of human ancestors tens of millions of years ago by ancient retroviruses, and has survived intact even into the modern age.

In the past most of this genetic material was dismissed as “junk” DNA, meaning it was thought to stay inactive and not contribute to human development or metabolism in any way. But in a new article just published in Science Advances, the UC Boulder scientists demonstrate that at least some of this DNA plays a vital role in the growth and proliferation of cancer cells, which means this incredibly old DNA is also incredibly dangerous when it is activated.

“Our study shows that diseases today can be significantly influenced by these ancient viral infections, that until recently very few researchers were paying attention to,” study senior author Edward Chuong, an assistant professor of molecular, cellular and developmental biology, explained in a University of Colorado-Boulder press release.

Remarkably, about eight percent of the entire human genome consists of genetic material associated with ancient retroviruses. These ancient invaders colonized the bodies of our primate ancestors, and their genes have been preserved even through those primates’ eventual transformation into new species, including Homo sapiens.

Edward Chuong and Atma Ivancevic at the BioFrontiers Institute. (Glenn Asakawa/CU Boulder)

How a Virus from 30 Million BC is Causing Human Health Problems Today

Ancient DNA from retroviruses cannot produce new viruses. What it does instead is play the role of a genetic “switch,” turning on other nearby genes and then amplifying their activity, if not all the time, then at least in certain circumstances.

While much of this material was previously dismissed as junk DNA, recent research, including some carried out by Edward Chuong at the UC Boulder Biology Department’s BioFrontiers Institute, has demonstrated some beneficial effects. For example, in the past some retroviral genes played a role in the evolution of the human placenta, which represented a huge step forward in human evolution. In the present day some of this retroviral DNA has been shown to stimulate activity in the human immune system, increasing our resistance to modern viral infections.

“There’s been a lot of work showing these endogenous retroviruses can be domesticated for our benefit, but not a lot showing how they might hurt us,” Chuong stated, acknowledging the uniqueness of his team’s findings.

 

Scrutinizing Cancer in Human DNA

To achieve this breakthrough in understanding about how some human cancers develop, Chuong and his research associate (and lead study author) Atma Ivancevic scrutinized genetic data obtained from the study of 21 human cancer types ih laboratories all over the world. They were looking for evidence of retroviral involvement, and they found it in relationship to the ancient retrovirus LTR10, which first infected the early primate population about 30 million years ago.

During their analysis, the researchers noted that LTR10 had been found to be highly active in people who had been diagnosed with several deadly types of cancer, including colon and lung cancers. When looking at data collected from the study of tumors of colorectal cancer patients, they discovered that LTR10 had been found to be active in more than 30% of cases.

Wanting to test their findings to make sure they were drawing the right conclusions, Chuong and Ivancevic used CRISPR gene-editing technology to remove or deactivate LTR10 sequences in active cell cultures taken from colorectal cancer tissues. When they did this, they found that other genes known to promote cancer cell growth immediately ceased functioning. This proved that activity in the LTR10 genes was indeed stimulating cancer growth in a measurable and detectable way.

“We saw that when you silence this retrovirus in cancer cells, it turns off nearby gene expression,” Ivancevic confirmed.

The researchers backed up these findings by performing experiments on genes taken from mice, and once again discovered that deactivating LTR10 halted the growth of cancer cells. Chuong explains:

“We know that cancer cells express a lot of genes that are not supposed to be on, but no one really knows what is turning them on. It turns out many of the switches turning them on are derived from these ancient viruses.”

The researchers are careful to note that retrovirus DNA would not be the only genetic “switches” implicated in the growth of cancerous tumors. They would be one type of driver, but not the only one. Nevertheless, this new research is vitally important, because up to now scientists didn’t know that ancient viral material was a contributing factor at all.

LTR10 Can Be Deadly … and it is Likely Not Unique

The study authors explain that LTR10 is just one type of ancient primate retrovirus. And yet it apparently helps to trigger or regulate up to 70 genes known to be involved in the ongoing development of cancer.

Given the high and dangerous potency of LTR10, it is reasonable to assume, the researchers say, that other types of ancient retroviruses are likely also implicated in the development of different forms of cancer. Of course, the only way to find out for sure is to actually look for such relationships, and that is exactly what the research team responsible for this new discovery intend to do.

“Any time we can find out how genes or pathways that are inherently altered in tumors are regulated, that is really helpful,” said study co-author Todd Pitts, an associate professor of medical oncology at the Colorado University Cancer Center on the Anschutz Medical Campus. “It allows us to potentially find new therapies or find patients that might respond better to current therapies.”

Edward Chuong suggests that ancient retroviral genetic material may be linked to the development of other kinds of diseases and serious health problems, beyond just cancer. His research team has only just begun to explore such questions, and the success they’ve had already will undoubtedly spur other scientists to launch their own studies into the influence of ancient retroviral DNA on hazardous health conditions.

Top image: DNA strand and Cancer Cell Oncology Research Concept 3D rendering               Source: catalin/Adobe Stock

By Nathan Falde