# The Role of Retroviruses in Evolution: Understanding the Placenta
Written on
Chapter 1: Understanding the Placenta
The placenta is a remarkable temporary organ that acts as the infant's respiratory system, nutritional source, and waste disposal unit. This life-sustaining structure allows two genetically distinct organisms to thrive within a single body until birth. Kelsey Coolahan, a medical student at Rowan University, highlights the unique immunological challenge this presents: "If you were to implant a piece of someone else's tissue under your skin, your body would reject it within days."
The coexistence of mother and fetus is facilitated by a specialized placental layer known as the syncytiotrophoblast, which is governed by the syncytin gene. "This barrier ensures that the mother and baby function together without attacking each other," Coolahan states, emphasizing the uniqueness of this structure in the human body.
Section 1.1: The Evolution of the Placenta
The placenta emerged in mammals roughly 130 million years ago, marking a significant evolutionary shift from egg-laying to live birth. This transition is attributed to the syncytin gene, responsible for producing syncytin proteins that form the syncytiotrophoblast layer.
In 2000, researchers at the Genetics Institute in Cambridge, MA, conducted a genomic analysis and discovered that the syncytin gene is derived from the envelope (env) gene of the human endogenous defective retrovirus (HERV-W). The authors noted that this retroviral envelope protein had been adapted during evolution for human use.
The env gene encodes a viral envelope composed of lipids similar to our own cell membranes. This viral envelope facilitates the fusion of the virus with host cells while simultaneously evading the host's immune response. It is theorized that this mechanism was repurposed for the syncytiotrophoblast to seamlessly integrate with the uterine lining without triggering an immune attack from the mother. "The fusiogenic and immunosuppressive properties of endogenous retroviruses are evidently the reason we were born," concludes Joachim Denner from the Robert Koch Institute in Berlin.
Coolahan elaborates, "Viruses merge with cells to infect them. Now, we have viral DNA that enables us to produce a protein capable of fusing cells."
The Cambridge team also demonstrated that inserting the env gene into human cells equipped them to create syncytin protein and fuse with other cells. Their groundbreaking paper in Nature was titled: "Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis."
Section 1.2: Syncytin's Role Beyond the Placenta
Interestingly, syncytin also plays a vital role in muscle repair and regeneration, specifically in males. Removing this gene results in a noticeable reduction in muscle mass in male mice. Similar effects have been observed in cultured myoblasts from sheep, dogs, and humans. The authors of this study noted, "These results indicate a direct role for fusogenic syncytins in muscle development, showing a male-specific effect in mice."
This observation leads to a consideration of sexual dimorphism, which refers to the differences in characteristics between males and females, excluding reproductive organs. This implies that the syncytin gene may have been adapted for placental fusion in females and muscle cell fusion in males.
Chapter 2: Birth Timing and Retroviral Influence
In 2018, researchers from the University of Cincinnati College of Medicine and the National Institutes of Health uncovered another retroviral component critical for regulating birth timing.
They initially focused on the role of corticotropin-releasing hormone (CRH), produced in large quantities by the primate placenta as pregnancy advances. The regulation of CRH is crucial, as improper levels can lead to premature or overdue births.
The team discovered that CRH expression is influenced by a nearby gene sequence of retroviral origin, known as transposon-like human element 1B (THE1B), derived from the long terminal repeat (LTR) of an unidentified ancient retrovirus. "Without this LTR gene, animals are unable to produce a placenta," explains Edward Chuong, a computational virologist reviewing the findings.
Chuong highlights the significance of these findings: "Human pregnancy would be vastly different—possibly even non-existent—if not for the retroviral pandemics that have impacted our evolutionary ancestors."
- .. youtube:: video_id
width: 800 height: 500
Section 2.1: Retroviruses as Evolutionary Drivers
Retroviruses like HIV can insert their genetic material into a host cell's genome, allowing the host to express viral proteins as if they were its own. If a retrovirus infects the genetic material of a sperm or egg, its sequences can be inherited by future generations.
Therefore, retroviruses play a significant role in evolution. As Aris Katzourakis, a professor of evolution and genomics at the University of Oxford, remarks, "Viral proteins already have established functions. It's far simpler to utilize these than to create them from scratch."
The syncytin and THE1B genes in mammals are examples of genetic material borrowed from retroviruses. Interestingly, recent studies indicate that retroviral sequences are also present in the genomes of certain placenta-bearing fish and reptiles.
Another notable instance of functional borrowing from retroviruses is the Arc gene, which is crucial for neuron communication and neuroplasticity, underscoring the evolutionary impact of these viruses on the development of the brain in land animals, including humans.
Section 2.2: The Complexity of Retroviral Integration
However, the integration of retroviral functions into the host genome is relatively rare, as compatibility is not always guaranteed. Approximately 8% of the human genome consists of retroviral sequences, but many of these are considered "junk DNA" or non-functional remnants.
For example, the gag and pol genes of retroviruses, located alongside the env gene, have also been integrated into the human genome, yet they serve no discernible purpose. Nonetheless, the influence of retroviruses on brain evolution and placental development remains a fascinating testament to the complexities of nature.