Study Reveals Key to Immune System Evolvability
A new study by Technion investigators uncovered an important evolutionary principle that allows the immune system to continually adapt and evolve through genetic variation. The findings, published on June 12, 2024 in Nature, show that genes involved in the interactions between different immune cell types play a crucial role in underlying the "evolvability" of the immune system. The study was led by Professor Shai Shen-Orr, Dr. Tania Dubovik, and postdoctoral fellow Dr. Martin Lukačišin from the Ruth and Bruce Rappaport Faculty of Medicine, in collaboration with Rambam Health Care Campus and Carnegie Mellon University.
"For evolution to occur through natural selection, there needs to be genetic variation that creates differences in traits like immunity between individuals," explained Shai, "Our study identified genes that influence the frequencies of various immune cell types in mice, and we found that a subset of these genes enhances evolutionary adaptability in a unique way."
Specifically, the team discovered that around 10% of the genes associated with immune cell frequencies were not actually expressed within those cell types themselves. Instead, these genes were expressed in other cell types and influenced the target cells through interactions.
"Remarkably, we found that the coding sequences of these 'cross-talking' genes have experienced weaker negative selection pressures during vertebrate evolution compared to genes acting within the same cell type," said Shai. "This suggests that mutations in genes governing intercellular interactions are more likely to create small, functionally viable changes in immune profiles that can act as the raw material for subsequent evolution by natural selection."
The study also revealed that genes associated with coordinating the frequencies of multiple immune cell types, which may regulate broader immune system dynamics, similarly harbored more genetic variation over evolutionary time.
"Our findings indicate that the immune system has evolved an elegant modular architecture that enhances its evolvability," Shai explained. "While the core machinery within cell types has been tightly conserved, the interactions between cell types provide an opportune area for functional experimentation through mutation and genetic diversity."
The authors propose that the immune system's multilayered modularity, facilitating genetic variation through intercellular interactions, has been a key factor enabling its rapid evolutionary adaptation to ever-changing pathogen threats.
"This principle of enhancing evolvability through modularity could extend to other complex biological systems and even provide insights for evolutionary design approaches in engineering," Shai said.
Source: Dubovik T, Lukačišin M, Starosvetsky E, LeRoy B, Normand R, Admon Y, Alpert A, Ofran Y, G'Sell M, Shen-Orr SS. (2024) Interactions between immune cell types facilitate the evolution of immune traits. Nature. Jun 12. doi: 10.1038/s41586-024-07661-0.
