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Deitsch, K. W., Lukehart, S. A., & Stringer, J. R. (2009). Common strategies for antigenic variation by bacterial, fungal and protozoan pathogens. Nature reviews. Microbiology, 7(7), 493–503. https://doi.org/10.1038/nrmicro2145
Pathogens are infectious agents such as bacteria, fungi, and protozoa (a type of single-celled microorganism) that cause disease to the organism that they are infecting, called their host. In humans, oftentimes pathogens can invade our bodies and lead us to fall ill. However, our bodies have immune systems in charge of fighting off pathogens; specific cells called B lymphocytes develop antibodies, proteins that allow the body to remember previous invading pathogens. Many substances, called antigens, can incite the formation of antibodies due to the body recognizing them as foreign. Viruses, a type of pathogen, are one such example. The immune systems of mammals are increasingly becoming stronger and smarter as they adapt to pathogens, but these pathogens are also evolving alongside them in a process called coevolution.
One such way that pathogens evolve to become more virulent (disease-causing) is through antigenic variation, where a pathogen alters the proteins present on its coat to deter an immune response from its host. Recall that antibodies allow immune systems to remember the proteins of previous pathogens, but if the proteins of the virus were to change, then the immune system would not be able to identify them.
One strategy of antigenic variation is phase variation, where a pathogen turns on/off certain gene expressions by controlling gene transcription (the process of copying genetic information from DNA to encode proteins). The genes encoding molecules that the immune system recognizes can stop being translated under phase variation, preventing a response from the immune system.
Some processes under antigenic variation involve altering the organism’s DNA, but many others have been found to not involve any changes to DNA, which is called epigenetic modification.
Genetic modification, on the other hand, involves direct changes to DNA. One way to think of epigenetic modification is by thinking of a light switch. Epigenetic modification may turn on or off gene transcription—like turning on and off a light—but it is not permanent, similar to how flipping a light switch does not cause a permanent state of light being on or off. Whereas, genetic modifications are permanent. Some examples of epigenetic modification include histone modification (proteins that provide structure for a genome), modifying the building blocks of DNA (nucleotides), and changes in the arrangement of DNA in the cell’s nucleus. Histone modification can occur in two major ways. The first is acetylation, in which the histone is loosened, allowing transcription factors (proteins involved in transcription) to get access to the DNA. This activates gene transcription. The second is methylation, in which the histone is tightened, limiting access to the DNA. This deactivates gene transcription. None of these examples of epigenetic modification change the pathogen’s DNA, but they lead to different genetic functions. For example, sometimes in antigenic variation, the order of the encoding genes is altered to change the expression of each pathogenic variant. These alterations can lead to a longer lasting infection of a host, increasing the chance of transmission to other hosts.
When a host has recovered from an infection or is suffering from an infection unceasingly (superinfection), antigenic variation of the same infecting pathogen can lead to a greater ability to reinfect the host. This genetic race between host immune systems and pathogens is progressing into the future, leading to more and more focus by researchers on studying coevolution.
Summarised by Jeannine Yu
Works Cited
“Histone Methylation.” Histone Methylation – an Overview | ScienceDirect Topics, https://www.sciencedirect.com/topics/neuroscience/histone-methylation.
“Histone.” Genome.gov, https://www.genome.gov/genetics-glossary/histone.
“The Immune System.” The Immune System | Johns Hopkins Medicine, 5 Jan. 2022, https://www.hopkinsmedicine.org/health/conditions-and-diseases/the-immune-system.
“NCI Dictionary of Cancer Terms.” National Cancer Institute, https://www.cancer.gov/publications/dictionaries/cancer-terms/def/transcription.
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