Endogenous retroviruses (ERVs) are components of our genetic makeup, remnants of ancient viral infections permanently integrated into our ancestors’ DNA. These “viral fossils” are inherited sequences, passed down through generations. ERVs are essentially genetic echoes of past encounters with retroviruses, now silent or repurposed elements within our own cells.
How Viruses Became Permanent Parts of Our DNA
The journey of a virus becoming a permanent part of our DNA begins with an exogenous retrovirus. Unlike DNA viruses, retroviruses carry their genetic material as RNA. To integrate into a host cell’s genome, these viruses employ an enzyme called reverse transcriptase, which transcribes their RNA into a DNA copy. This viral DNA, known as a provirus, then integrates into the host cell’s nuclear genome.
Most retroviral infections target somatic cells, which are not passed on to offspring. However, on rare occasions, a retrovirus can infect germline cells. If this germline infection occurs and the infected cell successfully contributes to a new organism, the viral DNA becomes an integral part of that organism’s genome. This sequence is then passed down, becoming an endogenous retrovirus.
Where These Viral Remnants Reside
Endogenous retroviruses are more prevalent in our DNA than many assume. These sequences constitute a substantial portion of the human genome. Estimates suggest that ERVs make up about 5% to 8% of our DNA, with some reports indicating up to 8% of the human genome is composed of these viral-origin sequences. This is a significant amount, considering that protein-coding genes account for only about 1% to 2% of our genome.
These ancient viral elements are widely distributed across different chromosomes. While many ERVs have accumulated mutations over millions of years, rendering them incapable of producing functional viral particles, their presence reflects past infections that have shaped our genetic landscape. This widespread distribution highlights their deep intertwining with our own genetic material.
The Surprising Roles of Endogenous Retroviruses
Endogenous retroviruses can play diverse roles in the host, ranging from beneficial to potentially detrimental. One beneficial function is their involvement in mammalian placenta formation. Specific ERV envelope proteins, known as syncytins, facilitate the fusion of cells to create the syncytiotrophoblast layer, which is important for nutrient exchange and protecting the fetus from the mother’s immune system during pregnancy. This “domestication” of viral genes for a host physiological process is an example of co-option in evolution.
ERVs also influence gene regulation, with their long terminal repeat (LTR) sequences often acting as promoters or enhancers for nearby host genes, affecting their expression in a tissue-specific manner. Some ERVs have also been found to contribute to the immune system’s function, playing a role in defense against certain bacterial and viral pathogens by promoting antibody production.
However, ERVs can also have detrimental effects. Their aberrant expression has been linked to various diseases, including certain cancers and autoimmune disorders. For example, specific human endogenous retroviruses, such as HERV-W and HERV-K, have been implicated in neurological conditions like multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). The activation of ERVs can also be triggered by exogenous viral infections, potentially contributing to inflammatory responses and disease progression.
Unlocking the Secrets of Our Viral Past
Scientists are actively studying endogenous retroviruses to better understand their impact on human health and evolution. Modern genomic sequencing technologies and bioinformatics tools are important for this research. These tools allow researchers to analyze ERV sequences within our genome, identifying their locations, structures, and patterns of expression.
Ongoing research aims to illuminate the precise mechanisms by which ERVs influence host gene expression, contribute to physiological processes, and potentially predispose individuals to certain diseases. Understanding these ancient viral elements provides insight into our evolutionary history and the dynamic interplay between viruses and host genomes. Continued studies promise to reveal more about the complex roles ERVs play in health, disease, and genetic diversity.