Scientists have found a link between the development of embryos and a viral infection that occurred 500 million years ago

During embryonic development, there is a crucial stage that has been associated with a virus that merged with the ancestral DNA of complex organisms. This virus is thought to have infected the earliest life forms on Earth and has left markers in our DNA. In fact, it is estimated that genetic material from these endogenous retroviruses makes up around 8 to 10 percent of the modern human genome.

According to researchers from the Spanish National Cancer Research Center (CNIO), this newly discovered link between these viruses and embryo growth has significant implications for creating artificial embryos and developing regenerative medicines.

“Until recently, these viral remnants were considered to be junk DNA, genetic material that was unusable or even harmful,” says biologist Sergio de la Rosa, from CNIO.

“Intuitively, it was thought that having viruses in the genome could not be good.”

By examining mice models in detail, the research team identified a retroviral protein named MERVL-gag, which aids in controlling the rate of embryo development just a few hours following fertilization.

The critical stage at hand is when the initial totipotent cells (which can develop into any cells that make up the entire organism) generate pluripotent cells (which can develop into cells that form any tissues of the body except placental tissue).

This gradual process of specialization in the embryo is responsible for converting a cluster of cells into a human, a sea cucumber, an earthworm, or a cat. The researchers demonstrated how MERVL-gag affects a gene called URI, which is believed to be critical in enabling molecules to become pluripotent.

“It is a totally new role for endogenous retroviruses,” says Djouder. “We discovered a new mechanism that explains how an endogenous retrovirus directly controls pluripotency factors.”

The research team discovered that the MERVL-gag protein has high levels of expression during the early totipotency phase of embryo growth. As the URI gains more influence over the behavior of cells, the levels of MERVL-gag protein decrease steadily. This delicate balance between proteins, genes, and pluripotency has evolved over hundreds of millions of years, and it owes its existence to an ancient virus.

This discovery is a crucial step in the process of developing artificial embryos successfully. It can also help with understanding problems that affect fertility and pregnancy.

“We are starting to realize that these retroviruses, which have co-evolved with us over millions of years, have important functions, such as regulating other genes,” says de la Rosa. “It’s an extremely active field of research.”

This news is a creative derivative product from articles published in famous peer-reviewed journals and Govt reports:

1. L. T. Gou, D. H. Lim, W. Ma, B. E. Aubol, Y. Hao, X. Wang, J. Zhao, Z. Liang, C. Shao, X. Zhang, F. Meng, H. Li, X. Zhang, R. Xu, D. Li, M. G. Rosenfeld, P. L. Mellon, J. A. Adams, M. F. Liu, X. D. Fu, Initiation of parental genome reprogramming in fertilized oocyte by splicing kinase SRPK1-catalyzed protamine phosphorylation. Cell 180, 1212–1227.e14 (2020).
2. S. Collombet, N. Ranisavljevic, T. Nagano, C. Varnai, T. Shisode, W. Leung, T. Piolot, R. Galupa, M. Borensztein, N. Servant, P. Fraser, K. Ancelin, E. Heard, Parental-to-embryo switch of chromosome organization in early embryogenesis. Nature 580, 142–146 (2020).
3. M. Borsos, S. M. Perricone, T. Schauer, J. Pontabry, K. L. de Luca, S. S. de Vries, E. R. Ruiz-Morales, M. E. Torres-Padilla, J. Kind, Genome-lamina interactions are established de novo in the early mouse embryo. Nature 569, 729–733 (2019)
4. M. Goolam, A. Scialdone, S. J. L. Graham, I. C. Macaulay, A. Jedrusik, A. Hupalowska, T. Voet, J. C. Marioni, M. Zernicka-Goetz, Heterogeneity in Oct4 and Sox2 targets biases cell fate in 4-cell mouse embryos. Cell 165, 61–74 (2016).
5. F. Yang, X. Huang, R. Zang, J. Chen, M. Fidalgo, C. Sanchez-Priego, J. Yang, A. Caichen, F. Ma, T. Macfarlan, H. Wang, S. Gao, H. Zhou, J. Wang, DUX-miR-344-ZMYM2-mediated activation of MERVL LTRs induces a totipotent 2C-like state. Cell Stem Cell 26, 234–250.e7 (2020).

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