By Adaora Belonwu
Published 11:57 PM EST, Wed April 28, 2021
Introduction
Evolution can be defined as the biological process by which the physical characteristics of creatures change over time, new types of creatures develop, and others disappear. Even before the recent coronavirus outbreak, the World Health Organisation revealed that three infectious diseases ranked among the top 10 leading causes of death worldwide in 2016. For such reasons, among many others, it has become almost second nature to regard viruses as the enemy of evolution, an arm’s race between a host and a pathogen*. Others may consider viruses as a potential catalyst in evolution, creating a selection pressure within a population where only the fittest survive. However, the process of evolution by natural selection also relies on extensive genetic diversity within a population, caused by mutation, in the hope that one of these mutations will allow the organism to survive despite the change in environment. This article will explore the role of viruses in creating genetic diversity and provoking the emergence of adaptations that allowed Homo Sapiens to evolve as a species. In particular, this article will discuss the importance of endogenous retroviruses (ERV) in the development of the placenta in mammals, the increased sophistication of the human brain, and the significance of ERV within an embryo’s fledgling immune system.
We’re All Part Virus. How?
After having successfully evaded our first line of physical defenses, retroviruses such as HIV infect our cells and create a DNA copy of their RNA genome and insert it into the host cell chromosome. Subsequently, upon the reproduction of the infected cell by mitosis, the viral DNA is copied also. If that happens in a gamete, it creates the potential for this viral DNA to be passed on from generation to generation. The host’s offspring inherits viral DNA in all of their cells and will pass this viral DNA to all of their descendants. Thus, an exogenous retrovirus (XRV) becomes endogenous (ERV). Whilst scientists do not believe this has happened with HIV, it has cast a new light on our understanding on the development and origins of certain features that characterise us Homo Sapiens as a species today. In fact, this has happened on many other occasions of evolution since our DNA is believed to be composed of at least 8% ERV DNA. Furthermore, ERVs are a subset of a larger class of mobile genetic elements, transposons (they move around DNA). It can be assumed that the outcome of transposons was the creation of genetic diversity that secured the survival of our ancestors.
Viruses And The Placenta During The Evolution Of Mammals
The survival of our population is dependent on the successful development of a fetus within its mother’s womb and its subsequent birth. This is enabled by the placenta, an organ that evolved during the emergence of mammals, without which we would have never been born. The placenta is a transient organ that mediates the transfer of nutrients and hormones between fetus and mother during intrauterine life whilst keeping their blood supplies. Its formation begins after the embryo implants into the womb, where finger-like projections burrow into the maternal tissue and alter its blood vessels so that they become bathed in a constant supply of the mother’s blood. This interface is what allows mother and fetus to exchange nutrients and waste yet such close contact means that the mother’s immune system could attack the developing embryo, which it sees as a foreign invader. As the first line of defense, the fetal cells along this boundary fuse together using a protein called syncytin. This removes any gaps where maternal white blood cells could squeeze through and launch an attack. Such an innovative mechanism can be attributed to endogenous retroviruses.
Syncitin was originally a viral protein that facilitated the infection of host cells by allowing viruses to fuse with cells. Sometime in the past, the gene encoding the syncytin protein was inserted into the host genome laying dormant for years until eventually becoming repurposed by evolution to fuse cells together in the placenta. It is estimated that this happened several times, leading to the development of the placenta on at least 6 different occasions. Moreover, it is interesting to consider that fetuses behave quite similarly to a virus, in which it develops inside a host organism trying to avoid detection from its immune system. So perhaps it is fitting that syncytin, which helps the fetus ‘invade’ the womb, once helped a virus invade a host. However other studies have been inconclusive in proving the existence of syncytin in other mammals such as pigs and horses, suggesting that the protein might not be an integral factor in the intrauterine development of fetuses. Nonetheless, recent experiments have not only corroborated the role of syncytin in the development of the placenta in most mammals but also link it to gestational immunosuppression in mice. Therefore, if the ancestors of pigs and horses were not infected with an ERV then they may at least use retroviral proteins to prevent the mother’s cells from attacking the fetus during pregnancy. Thus, viruses played a significant role in evolution by increasing the likelihood of a successful pregnancy so that our ancestors with the adaptations most suited to their surroundings could pass on their genes.
Could The Immune System Be A Relic Of A Viral Infection?
If ERVs play a role in gestational immunosuppression that begs the question of whether they play a role in the somatic immune system. This was proven to be the case for embryos. A human ERV known as HERV-K codes for a protein which aids it in making viral copies and proteins so that it can infect other cells. These trigger embryonic cells to make their own anti-viral proteins that build one of its first defences against other viruses. Whilst being far from a fully-fledged immune system this may make the difference between a successful pregnancy or not. Therefore, viruses help embryos develop a primitive immune-like-system that protects them prior to the development of antibodies to pathogens in the external environment. Furthermore, while ironic, it is feasible to extend this idea to the rest of our lifespan: our immune system may exist as a consequence of an infection of a retrovirus millions of years ago. So, in response to a selection pressure created by viruses, our immune systems now serve to protect us from things that may have very well lead to its creation.
Are Viral Relics Controlling Our Brains?
Linking to the notion of viruses equipping us to become the fittest and survive, researchers have proven that ERVs also played a role in the increased sophistication of the human brain. The brain is an important aspect to consider in human evolution because they would have been helpful some 60,000 years ago when homo sapiens coexisted with other larger, more aggressive hominid species. A more sophisticated cerebrum would have made early homo sapiens more flexible to environmental changes, allowing them to adapt their behaviour and food sources using information stored in their long term memory, ultimately increasing their likelihood of survival to reproductive age and produce fertile offspring. A gene, which scientists have named Arc, the mRNA and proteins it is subsequently transcribed and translated into have been proven to accumulate in dendrites. The protein was later shown to self-assemble into virus-like capsids that encapsulate RNA and were capable of trafficking across synapses in a similar fashion to neurotransmitters. This indicates that the Arc gene is a remnant of an ERV, potentially used first to protect the virus from a host’s attack but later repurposed by the human body. Further evidence of the human body potentially repurposing viral genes was proven in another study where the inhibition of the expression of the Arc gene in the rat hippocampus impaired the long-term memory and potentiation in the rat hippocampus. Moreover, evolutionary analysis indicates that Arc is derived from ancestors to retroviruses. This may indicate an initial dependence on the presence of functional ERV RNA for the development of long-term memory. Furthermore, a correlation between excess Arc and cases of brain disorders (such as Alzheimer’s and schizophrenia) has been observed. This, as well as the fact that the aforementioned experiments studies are relatively new and their result is yet to be repeated, leads to some doubt on the theory that viruses are solely responsible for the increased sophistication of the human brain. Nonetheless, considering the evidence of our reliance on microbes elsewhere in the body (such as the placenta and microbiome) the hypothesis that an ERV played a significant role in our ability to retain information for extended periods of time remains valid.
Conclusion
To conclude, viruses have and will continue to play a considerably large yet elusive and understated role in the evolution of humans, as well as many other animals. Their nature to inject themselves into the genome of their hosts on the off chance that they might cross paths with a germline cell allows their genes to be passed down through generations, essentially preserving their genome ad finitum. Despite the minuscule sounding 8%, endogenous retroviruses have managed to influence important adaptations such as the placenta, embryonic immunity, and memory. Viruses have influenced all aspects of evolution, whether it be the selection pressure prerequisite for natural selection or mutations that allowed us to adapt to those selection pressures. So perhaps in lieu of considering the most physically menacing creatures as winners of evolution perhaps it’s time to scale down our gaze and consider these tiny, often deadly biological particles as the ‘fittest’ in a Darwinian competition for survival.
Adaora Belonwu, Youth Medical Journal 2021
References
Alberts, B., 2002. Molecular Biology Of The Cell. New York: Garland Science, p.Introduction to Pathogens:
*pathogen meant as an infectious biological agent that causes disease, such as the prion responsible for BSE, otherwise known as ‘mad cow’, disease
DARWIN, C., 2019. ON THE ORIGIN OF SPECIES. [S.l.]: NATURAL HISTORY MUSEUM.
Denner, J., 2016. Expression and function of endogenous retroviruses in the placenta. APMIS, [online] 124(1-2), pp.31-43. Available at: <https://onlinelibrary.wiley.com/doi/full/10.1111/apm.12474>
Guzowski, J., Lyford, G., Stevenson, G., Houston, F., McGaugh, J., Worley, P. and Barnes, C., 2000. Inhibition of Activity-Dependent Arc Protein Expression in the Rat Hippocampus Impairs the Maintenance of Long-Term Potentiation and the Consolidation of Long-Term Memory. The Journal of Neuroscience, [online] 20(11), pp.3993-4001. Available at: <https://www.jneurosci.org/content/20/11/3993.short> .
Henzy, J., 2014. Retroviruses, The Placenta, And The Genomic Junk Drawer. [online] Small Things Considered. Available at: <https://schaechter.asmblog.org/schaechter/2014/06/retroviruses-the-placenta-and-the-genomic-junk-drawer.html>
Heron, M., 2020. Deaths : Leading Causes For 2016. [online] Stacks.cdc.gov. Available at: <https://stacks.cdc.gov/view/cdc/57988>
Kerrigan, T. and Randall, A., 2013. A New Player in the “Synaptopathy” of Alzheimer’s Disease – Arc/Arg 3.1. Frontiers in Neurology, [online] 4. Available at: <https://www.frontiersin.org/articles/10.3389/fneur.2013.00009/full>.
Kochiyama, T., Ogihara, N., Tanabe, H., Kondo, O., Amano, H., Hasegawa, K., Suzuki, H., Ponce de León, M., Zollikofer, C., Bastir, M., Stringer, C., Sadato, N. and Akazawa, T., 2018. Reconstructing the Neanderthal brain using computational anatomy. Scientific Reports, [online] 8(1). Available at: <https://www.nature.com/articles/s41598-018-24331-0>.
Mi, S., Lee, X., Li, X., Veldman, G., Finnerty, H., Racie, L., LaVallie, E., Tang, X., Edouard, P., Howes, S., Keith, J. and McCoy, J., 2000. Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis. Nature, [online] 403(6771), pp.785-789. Available at: <https://www.nature.com/articles/35001608>.
NELSON, P., HOOLEY, P., RODEN, D., DAVARI EJTEHADI, H., RYLANCE, P., WARREN, P., MARTIN, J. and MURRAY, P., 2004. Human endogenous retroviruses: transposable elements with potential?. Clinical and Experimental Immunology, [online] 138(1), pp.1-9. Available at: <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1809191/>.
Pastuzyn, E., Day, C., Kearns, R., Kyrke-Smith, M., Taibi, A., McCormick, J., Yoder, N., Belnap, D., Erlendsson, S., Morado, D., Briggs, J., Feschotte, C. and Shepherd, J., 2018. The Neuronal Gene Arc Encodes a Repurposed Retrotransposon Gag Protein that Mediates Intercellular RNA Transfer. Cell, [online] 173(1), p.275. Available at: <https://www.cell.com/cell/fulltext/S0092-8674(17)31504-0>.
Ashley, James, et al. “Retrovirus-like Gag Protein Arc1 Binds RNA and Traffics across Synaptic Boutons.” Cell, vol. 172, no. 1-2, 2018, doi:10.1016/j.cell.2017.12.022.
Bramham, Clive R, et al. “The Arc of Synaptic Memory.” Experimental Brain Research, Springer-Verlag, Jan. 2010, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2803749/.
Cornelis, Guillaume, et al. “An Endogenous Retroviral Envelope Syncytin and Its Cognate Receptor Identified in the Viviparous Placental Mabuya Lizard.” PNAS, National Academy of Sciences, 19 Dec. 2017, http://www.pnas.org/content/114/51/E10991.
DF;, Noronha LE;Antczak. “Maternal Immune Responses to Trophoblast: the Contribution of the Horse to Pregnancy Immunology.” American Journal of Reproductive Immunology (New York, N.Y. : 1989), U.S. National Library of Medicine, pubmed.ncbi.nlm.nih.gov/20618178/.
Youth Medical Journal 