🦠 Evolution: our immune defenses similar to those of... bacteria

In a study published in Nature Ecology and Evolution, scientists show that the SAMD9 and SAMD9L genes, key players in antiviral immunity in humans and involved in rare genetic diseases, share very strong similarities with defense systems present in bacteria.

Their evolution, marked by recent losses and adaptations in mammals, reveals the millennia-old arms race between viruses and hosts. In some primates, these evolutions provide better protection against HIV replication, opening avenues to better understand the subtleties of our immunity.

Ancient genes at the heart of antiviral defenses

Intracellular innate immunity is one of the organism's very first barriers against viruses. It relies on hundreds of proteins capable of detecting a pathogen (called sensors) and/or blocking its multiplication, the antiviral effectors.

Among them, the proteins encoded by the SAMD9 and SAMD9L genes play a key role in humans: they slow down the production of viral proteins, particularly those of poxviruses and lentiviruses like HIV. Dysregulation of these genes, caused by genetic mutations, can lead to serious pathologies, such as autoimmune diseases or certain cancers.

The study published in the journal Nature Ecology and Evolution sheds light on the evolutionary history of this gene family: duplications, losses, rapid evolution, all signs of constant selection pressures often exerted by viruses. This phenomenon illustrates a true evolutionary "arms race": viruses develop strategies to infect, while hosts strengthen their defenses, pushing each to constantly evolve.

From bacteria to primates, a convergent evolution of antiviral defenses

By combining genetic and structural analyses on public data from a wide range of species (bacteria, animals, including primates), scientists were able to show that proteins analogous to SAMD9 exist even in bacteria.

In bacteria, these proteins called Avs participate in defense against viruses that infect bacteria (bacteriophages). Laboratory experiments have shown that when an Avs9 (the most similar to SAMD9) is activated, it causes the death of the bacterium, an "altruistic suicide" that would prevent the spread of the virus. The structural resemblance to human SAMD9 proteins suggests convergent evolution: nature would have repeatedly found similar solutions to counteract viral infections, despite billions of years of separation between bacteria and mammals.

On a more recent scale, in primates, the evolution of these genes also reveals a conflict-ridden evolutionary past, with episodes of losses according to species. For example, although SAMD9 and SAMD9L are both essential in humans, bonobos, our close cousins, have lost SAMD9. This loss is recent and some individuals even still carry both genes, SAMD9 and SAMD9L.

In a surprising discovery, tests conducted by scientists on human cells show that the versions of the SAMD9L gene in chimpanzees and bonobos are more effective than the human one against HIV replication. These adaptations could reflect an adaptation to ancient lentiviruses, contributing to a form of natural resistance in these species.

This study thus reveals that our antiviral mechanisms have very ancient roots, similar even in the bacterial world, and that they continue to evolve in the face of viral threats.

Understanding these dynamics, which link ancestral defenses and modern adaptations, could one day inspire new therapeutic approaches against human viral infections, such as HIV.