From Viral Invaders to Evolutionary Enablers: Viruses and the Mammalian Placenta

Published by on October 26, 2023

The placenta is a fascinating organ: not only is it temporary, but it has also enabled animals to give birth to live offspring. In fact, it is the first organ to form in mammalian development, and its ancestral form developed approximately 130 million years ago (Chuong, 2018). The evolution of the placenta brought about the evolution of the trophoblast lineage, which separates embryonic cells to form differentiated cells that compose the placenta (Chuong, 2013).  Although vital to fetal development, this temporary organ is one of the least-understood of all mammalian organs; though its origins are still being studied, scientists speculate the placenta developed with the help of endogenous retroviruses.

How can viruses, supposedly unalive, play such a crucial role in mammalian development? Well, the answer is complicated. Endogenous retroviruses (ERVs) are a class of retroviruses that make up around 8% of the human genome (Mao, Zhang and Cong, 2021). They have been infecting vertebrates for over 450 million years by reverse transcribing their RNA into DNA and integrating it into the DNA of a host cell (Figure 1) (Chuong, 2018).

Figure 1. An infectious retrovirus particle enters the cytoplasm of a host cell. The viral capsid contains RNA that forms the genome of the retrovirus (red) and a reverse transcriptase (green). The genome of the retrovirus is reverse-transcribed into DNA and inserted into the genome of its host (Meyer et al., 2017).

Retrovirus particles and mRNAs are frequently detected in placentas, suggesting a distinctive attraction of these elements to the organ, and there seems to be evidence that changes in the genome of egg-laying mammals induced its formation (Haig, 2012; Chuong, 2013). Several ERV-derived genes through reverse transcription such as PEG10 and PEG11/RTL1 have been demonstrated to be crucial to placental development by aiding in the establishment and regulation of the organ (Imakawa et al., 2022). Another ERV-derived protein, Syncitin-1, promotes trophoblast fusion in vitro, a process crucial to development of the placenta (Figure 2) (Chuong, 2013).

Figure 2. Syncitin-1 is a protein transcribed by a gene derived from an endogenous retrovirus found in the mammalian placenta (Chuong, 2018).

ERV-derived genes have led to the evolution of mammalian birth, although the mechanism by which this happened is still a subject of intense study. For the genetic insertion to lead to evolution, its effects must be nearly neutral while not significantly influencing an individual’s fitness. Furthermore, its haplotype should increase in frequency by either the mechanism of genetic drift or hitchhiking (the mechanism by which certain alleles associated with another allele that has been selected also make it through selection) (Barton, 2000). On the other hand, if the insertion increases an individual’s fitness, its frequency should increase, leading to an adaptation. Either of these scenarios must have had to occur in originally egg-bearing mammals for them to eventually develop placentas (Haig, 2012).

In essence, placentas, the temporary organ that enables mammals to give birth to live offspring evolved thanks to the process of reverse transcription by retroviruses. It can be hypothesized that this occurred in egg-bearing individual mammals, later leading to evolution within the population. Despite the generally negative perception of viruses, it might be worthwhile to reassess their role in our survival, acknowledging their potential positive contributions to evolutionary processes.

References

Barton, N.H., 2000. Genetic hitchhiking. Philosophical Transactions of the Royal Society B: Biological Sciences, 355(1403), pp.1553–1562.

Chuong, E.B., 2013. Retroviruses facilitate the rapid evolution of the mammalian placenta. BioEssays, 35(10), pp.853–861. https://doi.org/10.1002/bies.201300059.

Chuong, E.B., 2018. The placenta goes viral: Retroviruses control gene expression in pregnancy. PLOS Biology, 16(10), p.e3000028. https://doi.org/10.1371/journal.pbio.3000028.

Haig, D., 2012. Retroviruses and the placenta. Current Biology, 22(15), pp.R609–R613. https://doi.org/10.1016/j.cub.2012.06.002.

Imakawa, K., Kusama, K., Kaneko-Ishino, T., Nakagawa, S., Kitao, K., Miyazawa, T. and Ishino, F., 2022. Endogenous retroviruses and placental evolution, development, and diversity. Cells, 11(15), p.2458. https://doi.org/10.3390/cells11152458.

Mao, J., Zhang, Q. and Cong, Y.-S., 2021. Human endogenous retroviruses in development and disease. Computational and Structural Biotechnology Journal, 19, pp.5978–5986. https://doi.org/10.1016/j.csbj.2021.10.037.

Meyer, T.J., Rosenkrantz, J.L., Carbone, L. and Chavez, S.L., 2017. Endogenous retroviruses: With us and against us. Frontiers in Chemistry, 5. https://doi.org/10.3389/fchem.2017.00023.