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Our ancient past isn't always buried history. When it comes to our DNA, nearly 9% of the human genome is made up of leftover genetic material from ancient viruses (called endogenous retroviruses or ERVs) that infected our ancestors millions of years ago and became permanently integrated into our genetic code. In a new study in the journal Nature, scientists have demonstrated that one piece of this viral junk is essential for the earliest stages of human life.

Knowledge of how ERVs affect human development is limited because scientists obviously cannot conduct ethical experiments on embryos. To overcome this, researchers in this study used human blastoids, 3D models grown from stem cells that mimic the structure and key cell types of a natural blastocyst. This is the ball of cells that form in early pregnancy, about five to seven days after fertilization.

Testing the role of viral DNA

The team focused on a specific type of ERV known as HERVK LTR5Hs, which were introduced into our DNA after our lineage split from Old World monkeys. Although this event occurred millions of years ago, it is considered relatively recent in evolutionary genetic terms.

To determine the functional effect of these viral remnants on the early embryo, the research team used cutting-edge genetic tools that act like molecular scissors to switch off LTR5Hs elements or delete them completely. The results were dramatic. The blastoids either died or turned into disorganized clumps. This provided clear proof that this ancient DNA is essential for the pre-implantation stage of human development.

The researchers also dug deeper to find out what was going on at the subcellular level. They discovered that the LTR5Hs elements act as powerful enhancers, boosting the activity of neighboring genes. When their activity is suppressed, many nearby genes associated with the epiblast (the cell layer that eventually forms the embryo) are turned down. That is, their activity is reduced. This showed that the viral DNA is directly responsible for controlling these essential early developmental instructions.

One of the most important discoveries involved the ZNF729 gene. The team found that one specific LTR5Hs insertion (an extra piece of DNA added to a DNA sequence), unique to humans, acts as a master key for activating this gene. Since the gene regulates fundamental cellular processes, such as cell growth and metabolism, the viral DNA master key is crucial to our development.

As senior author Joanna Wysocka commented, "Our results illustrate how recently emerged transposable elements and genes can confer developmentally essential functions in humans."

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