A million-year-old virus is now essential for embryo development

All animals certainly evolved hundreds of millions of years ago virus infected primitive organisms. The viral genetic material has been integrated into the genome one of the first multicellular creatures and still exists in our world today. DNA.

A study published in the journal Scientific advancesshows for the first time the role these viruses play in a key process of our development that takes place a few hours later fertilization: the transition to pluripotency, when the egg cell goes from two to four cells.

Before this step, each of the two cells of the embryo It is totipotent, meaning it could develop into an independent organism. Thus, the four cells of the next phase are not totipotent but rather pluripotent because they can differentiate into cells from any specialized tissue in the body.

For the authors, scientists at the National Cancer Research Center (CNIO), the finding is relevant to the field Regenerative medicine and in the creation of artificial embryos because it opens a new way to generate stable cell lines in the totipotency phases.

We are 8% retroviruses

The genetic material of so-called endogenous retroviruses has been integrated into the genome of the organisms that may be the protagonists of the retroviruses Cambrian explosiona time more than 500 million years ago when the planet's seas experienced an explosion in biodiversity.

Over the last decade, it has been discovered that the genetic sequences of these viruses make up at least 8-10% of the human genome.

Until recently, these viral remnants were considered junk DNA, i.e. useless or even harmful genetic material.

Sergio de la Rosa, first signee

“Until recently, these virus remnants were considered junk DNA, useless or even harmful genetic material,” he explains. Sergio de la RosaFirst signatory of the new article.

“Intuitively, people thought that having viruses in the genome couldn’t be good. But in recent years, we are realizing that these retroviruses, which have co-evolved with us over millions of years, perform important functions, such as regulating other genes. “It’s a very active field of research,” he adds.

Nabil Djouder, Head of the Growth Factors, Nutrients and Cancer Group at CNIO. / Antonio Tabernero. CNIO

The rhythm of embryonic development

The new research shows that the endogenous retrovirus MERVL sets the pace in embryonic development, particularly during the specific step of the transition from totipotency to pluripotency, and explains the mechanism by which this occurs.

“It’s a completely new role for endogenous retroviruses,” he says. Nabil Djouder, senior author. “We have discovered a new mechanism that explains how an endogenous retrovirus directly controls pluripotency factors.”

This new mechanism of action involves URI, a gene that Djouder's group is studying in detail. Years ago they discovered that when URI is eliminated in laboratory animals, embryos don't even develop. De la Rosa wanted to know why, and so he discovered its relationship to the MERVL retrovirus.

A smooth transition

Their results show that one of the functions of the URI gene is to enable the action of essential molecules to acquire pluripotency; If URI does not work, the pluripotency factors do not work either and the cell remains in a state of totipotency. In addition, it turns out that it is a protein of the endogenous retrovirus MERVL-gag, which in turn modulates the effect of URI.

These results demonstrate the symbiotic coevolution of endogenous retroviruses with their host cells to ensure a smooth and timely progression of early embryonic development.

Authors

Researchers have observed that during the totipotency phase (when there are only two cells in the egg), expression of the viral protein MERVL-gag is high; This protein binds to URI and prevents its action. But gradually the values ​​​​change so that the levels of the MERVL-gag virus protein decrease and URI can come into action: pluripotency occurs.

“It’s a smooth transition. If you have high viral protein expression, you have fewer pluripotency factors; When ERV expression decreases, let URI stabilize these factors,” says De la Rosa.

Further research required

For the authors, “these results demonstrate the symbiotic coevolution of endogenous retroviruses with their host cells to ensure the smooth and timely progression of early embryonic development.”

In other words, the three-way relationship between the viral protein, the URI, and the pluripotency factors is modulated very finely “to allow the embryo sufficient time to adjust the smooth transition from totipotency to pluripotency and cell lineage specification along the way.” to coordinate embryonic development,” continues Djouder.

Finally, although the presence of endogenous retroviruses and pluripotency factors in the human genome is well established, the researcher would like to clarify that, given that the present work was carried out with mouse embryos, “more research” is needed to ensure that the results are based on the can be transmitted to people.