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Zombies in Our Genes: How Retroviruses Shape Human Evolution and Potentially Aid Cancer Research
Context:
Most viruses do not significantly alter the host genome, retroviruses are an exception: they can integrate into and modify the genomes of the cells they infect.
The Role of Retroviruses:
- Integration into Genomes: Unlike most viruses, retroviruses can integrate their RNA genome into the DNA of the host cells. This process involves reverse transcriptase, an enzyme that converts viral RNA into DNA.
- Historical Discoveries: The ability of retroviruses to integrate and cause cancer was first observed in the early 20th century, with significant breakthroughs occurring in the 1970s and 1980s. Key discoveries include HIV, identified as a human retrovirus in 1983.
Retrovirus Life Cycle:
- Retroviruses integrate their reverse-transcribed DNA into the host’s DNA with the help of the enzyme integrase, forming a provirus. This process effectively turns the host cell into a factory for producing new viruses.
Zombie Regions & Endogenous Retroviruses (ERVs):
- While retrovirus infections are usually not inherited due to damage to a subset of cells, faulty integrations can leave behind ‘zombie’ regions in the host’s genome known as ERVs.
- These are remnants of ancient viral integrations that cannot replicate or produce functional proteins due to missing regulatory elements.
- These parts are called endogenous retroviruses (ERVs).
- If these integrations occur in germ cells (sperm or ova), ERVs can be passed to offspring. A germ cell transforms into a reproductive cell, known as an egg in females and a sperm in males. Over evolutionary timescales, ERVs can make up a significant portion of the genome, with approximately 8% of the human genome composed of ERVs.
Biomarker for Preeclampsia:
- Syncytins, genes derived from ERVs, are crucial for placental development, having evolved from viral envelope genes. Recent research published in Proceedings of the National Academy of Sciences identified an ERV-derived RNA that is dysregulated in early-onset preeclampsia, potentially serving as a biomarker for this condition.
Applications in Medical Research:
- Preeclampsia Biomarkers: ERVs might serve as biomarkers for conditions such as preeclampsia, a pregnancy complication characterised by high blood pressure.
- Colorectal Cancer: Specific ERV elements, like LTR10, may influence cancer formation. These elements could regulate gene expression related to tumour development.
Retroviruses:
- A retrovirus is a type of virus that has RNA as its genetic material.
- When it infects a cell, the cell converts the retroviral RNA into DNA.
- This DNA is then integrated into the host cell’s DNA, leading the cell to produce new retroviruses that go on to infect additional cells.
- Retroviruses are linked to several diseases, including AIDS and certain cancers.
