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Virus-Derived Domesticated Genes in Microglia and Resident Macrophages: Insights into Placenta-Driven Evolution in
Masahito Irie1,2, Fumitoshi Ishino1, Tomoko Kaneko-Ishino2
1Department of Epigenetics, Medical Research Institute (MRI), Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan.
Abstract:
Eutherian mammals possess 11 metavirus-derived genes, collectively known as the sushi-ichi retrotransposon homologue (SIRH)/Retrotransposon Gag-like (RTL) genes. Several members of this group function in microglia, where SIRH3/RTL6, SIRH8/RTL5, and SIRH10/RTL9 mediate innate immune responses against bacterial-, viral-, and fungal-derived pathogen-associated molecular patterns, respectively, whereas SIRH11/RTL4 responds to noradrenaline and is thought to contribute to stress-responsive brain functions. In addition, the retroviral Env-derived gene ERVPb1 has been implicated in yolk sac-derived resident macrophage lineages, suggesting that both Gag- and Env-derived domesticated genes contributed to the evolution of mammalian neuroimmune systems. Microglia are now recognized as central regulators of neural circuit formation, brain homeostasis, and neuroimmune function, and their dysfunction has been implicated in a wide range of neurological and psychiatric disorders. Here, we review current knowledge of virus-derived genes that have shaped the functional evolution of microglia. We also revisit the concept of "Placenta-driven evolution," which proposes that the relatively hypomethylated developmental environment of extraembryonic tissues, including the placenta and yolk sac, facilitates the retention and functional co-option of virus-derived sequences, thereby accelerating eutherian evolution. Finally, by integrating recent advances in virus-derived genes and retroelement biology, we discuss how this evolutionary framework may extend beyond extraembryonic tissues to other hypomethylated developmental environments, including the germline and preimplantation embryos.
Insights
Virus-derived genes, like sushi-ichi retrotransposon homologue (SIRH)/Retrotransposon Gag-like (RTL) genes, have shaped microglia evolution and neuroimmune functions in mammals. Placenta-driven evolution may facilitate this process.
Area of Science:
- Evolutionary biology
- Neuroimmunology
- Genetics
Background:
- Eutherian mammals possess 11 virus-derived genes (SIRH/RTL genes) involved in neuroimmune functions.
- Specific SIRH/RTL genes in microglia mediate responses to pathogens and stress.
- Retroviral Env-derived genes also contribute to macrophage lineages, highlighting dual origins of neuroimmune genes.
Purpose of the Study:
- To review the role of virus-derived genes in the functional evolution of microglia.
- To explore the concept of "Placenta-driven evolution" in shaping mammalian neuroimmune systems.
- To discuss the extension of this evolutionary framework to other hypomethylated developmental environments.
Main Methods:
- Literature review of current knowledge on virus-derived genes and microglia.
- Revisiting the "Placenta-driven evolution" hypothesis.
- Integrating advances in retroelement biology and neuroimmunology.
Main Results:
- SIRH/RTL genes play crucial roles in microglial innate immunity and stress response.
- The retroviral gene ERVPb1 is implicated in yolk sac macrophage lineages.
- Virus-derived genes have significantly contributed to the evolution of mammalian neuroimmune systems.
Conclusions:
- Virus-derived genes are integral to microglial function and mammalian neuroimmune evolution.
- "Placenta-driven evolution" provides a framework for understanding the co-option of viral sequences.
- This evolutionary mechanism may extend to germline and preimplantation embryos.
