New studies show that ancient viral DNA is key to regulating human embryo development. Specifically, it shows that almost 9% of the entire human genome is made up of traces of these prehistoric viruses. These remnants, called endogenous retroviruses (ERVs), were viruses that successfully inserted themselves into the genetic code of our human ancestors millions of years prior. Researchers the world over have come to realize LTR5Hs as being utterly crucial to the very beginnings of human life. This particular insertion is like a master key, turning on important genes necessary for formation of the embryo.
Research team headed by Raquel Fueyo. It went on to be published in the highly regarded journal Nature, with Joanna Wysocka as the senior author. Their findings point to the critical roles played by these viral elements, especially with respect to human embryonic development.
Understanding Endogenous Retroviruses
Endogenous retroviruses, or ERVs, are stretches of non-coding DNA that were once ancient viral infections that have integrated themselves into the human genome. These regulatory sequences, though frequently considered “junk” DNA, are absolutely essential to a multitude of biological processes. From an evolutionary perspective, however, these viral sequences had a much more recent origin. That would imply that their effects on human biology might still be a work in progress.
The research team zeroed in on a specific ERV insertion, LTR5Hs, that is found only in humans. This unusual viral element was discovered to serve as an activator of the ZNF729 gene, which is a crucial regulator in early embryonic development. This gene is indispensable for the formation of blastoids. These ball-like structures form in the early days of gestation, usually about five to seven days post-fertilization.
The Role of LTR5Hs in Embryo Development
Through their research, Fueyo and Wysocka used a pre-implantation model to investigate the role that LTR5Hs plays in guiding human embryo development. To do this, they used human naive pluripotent stem cells (hnPSCs)– cultured under conditions that promote their unlimited proliferation. The researchers made the surprising find that LTR5Hs activity is central to driving this blastoids formation potential of these stem cells.
The study took place snapshots ~80–103 h post plating of WT hnPSCs. These images made the deleterious effect of adding the LTR5Hs insertion substrate abundantly clear. Specifically activating the ZNF729 gene via LTR5Hs increases hnPSCs’ propensity to produce blastoids. This improvement is important for the implantation success and the embryo’s subsequent development.
Implications of Research Findings
The impacts of this research go well beyond just learning how early humans develop. Here, we misregulatory mechanism this study reveals, a human-specific mechanism, related to ancient viral DNA. Second, it draws attention to evolutionary adaptations unique to humans that may be lacking in other species. The incorporation and eventual triggering of activity of these viral sequences are an amazing part of human genetic development.
These findings can serve as a blueprint for reproductive health and developmental disorders future study. We are on the cusp of transformative innovations by studying ancient viral DNA’s effects on embryonic development. These findings have the potential to revolutionize fertility treatments and regenerative medicine.