Immune genes – important, yet not explored

An evolutionary symposium led by Michal Vinkler and Helena Westerdahl from Lund University summarized the main concepts in evolutionary immunology and explained where the gaps in current research are. This study was followed by many years of revisional and conceptual work by over twenty evolutionary biologists and immunologists, who were working under the guidance of doc. Vinkler. The result was an overall summary of the current knowledge on the evolution of immune genes in vertebrates and recommendations for future research on this topic.

Evolutionary immunology was created by combining comparative immunology and evolutionary ecology. It is a new dynamically evolving field. Its goal is to understand molecular adaptations in immune genes that were caused by an interaction with a pathogen. Immunological reaction is about keeping balance in immunity, so that it protects the host, but doesn’t cause too much damage. That’s the reason why an organism will sometimes choose a defense reaction and sometimes just tolerates the pathogen and eliminates its effect on the organism. 

Immune genes aren’t very easy to define, but the term immunome has been used to describe genes that variously contribute to immunity. It includes core immunome, which is mainly responsible for recognition and response to pathogens. These genes have been, until now, studied the most, which has led to neglect of other immune genes. These consist of peripheral immunome, which connects immunity and other physiological functions, and so-called NIRGs. These non-immune resistance genes usually don’t contribute to immunity, but they are crucial in certain interactions (for example the binding of pathogen and host cell).

Based on their variability and dynamics, two types of immunity are usually defined – adaptive, which is evolutionarily younger, and innate, which is older. However, both systems are functionally interconnected and mostly differ in the origin of their receptors. Genes of adaptive immunity are linked with immunoglobulin receptors, which gain their structural variability independently in various types of lymphocytes during an organism’s life. On the contrary, genes of innate immunity are much more conservative in their function. Unfortunately, this categorization of immune genes doesn’t explain evolutionary changes, which are happening across species. They could be explained by categorizing genes based on their functional interactions with other molecules.

Despite their proximity to each other, related species can react very differently to the same pathogen. Image by pikisuperstar on Freepik

Repeating interactions with certain types of pathogens during phylogeny might cause the development of structurally similar molecules in unrelated organisms. Authors propose that higher genetic variability could exist in genes, that are encoding proteins, which interact with microbial molecules directly. That could make coevolution between host and pathogen faster. When the interaction is only with its own molecules, or conservative molecules of the host, the evolution of genetic variability isn’t so intense. Another factor could be the environment of protein interactions. Extracellular proteins are facing a very heterogeneous environment and therefore are undergoing stronger selection than cytosolic proteins. It can be also expected that constitutively expressed proteins will have lower adaptive genetic variation than defense proteins, whose production starts after contact with the pathogen. Last but not least, binding specificity might affect the intensity of selection.

Immune genes can be studied within species, on the microevolutionary scale, or between species, on the macroevolutionary scale. Within-species approach is often easier because there are more shared genes that can be studied. Despite this, even related species can react differently to one pathogen. Moreover, inter-population variability within species can have a similar effect. We have seen this during the epidemic of COVID-19. It also gives insight into how immune genes change over time, mostly thanks to long-term studies, which can be crucial in epidemics of various infections. Furthermore, the macroevolutionary scale reveals the functional relevance of immune genes in different species. Gene families are usually not lost, but they are often modified.

Adaptive changes happening during evolution form the immune system, which is in balance with the surroundings – not only pathogens but other microbes as well. Although understanding the principles of immune gene evolution is crucial for understanding our relationship with the environment and the ability of different species to protect themselves from infectious diseases, most immune genes have not been studied from an evolutionary perspective. The authors of this research paper recommended that scientists from different disciplines should come together and form collaborative networks to advance our understanding of the evolution of immune genes.

Eliška Leštinová

Vinkler, M., Fiddaman, S. R., Těšický, M., O’Connor, E. A., Savage, A. E., Lenz, T. L., Smith, A. L., Kaufman, J., Bolnick, D. I., Davies, C. S., Dedić, N., Flies, A. S., Samblás, M. M. G., Henschen, A. E., Novák, K., Palomar, G., Raven, N., Samaké, K., Slade, J. … Westerdahl, H. (2023). Understanding the evolution of immune genes in jawed vertebrates. Journal of Evolutionary Biology, 36, 847–873. https://doi.org/10.1111/jeb.14181