Autoimmune diseases rank among some of the most confounding problems for researchers looking into the causes of what makes people sick.
Why, of all things, would our bodies attack their own cells? At the Hutchinson Center, evolutionary biologist Dr. Harmit Malik and his colleagues think that when it comes to autoimmune diseases such as lupus, we may be looking at the remnants of lost evolutionary arms races.
“We want to determine whether autoimmunity—when the body’s immune system turns against itself—results from an evolutionary arms race between ancient parasitic genes and the defense mechanisms that control them, which could provide a new model for understanding what causes lupus,” Malik said.
Dr. Harmit Malik
The human genome is littered with parasitic “jumping genes,” or endogenous retroelements, which can replicate and re-insert themselves into DNA. During millions of years of evolution, most of these genes have lost their ability to jump, but a tiny fraction are still capable of becoming active.
Recently, it was discovered that some people with lupus carry a mutation in the TREX1 gene, which inhibits their body’s ability to recognize and attack these jumping genes when they become active. This led Malik and colleague Dr. Richard McLaughlin to theorize that autoimmunity may arise when cells can no longer recognize these jumping genes, or retroelements.
Malik recently received a $300,000 grant from the Lupus Research Institute to study the potential role of “genetic conflicts” in the development of lupus.
“The Lupus Research Institute grant will allow us to test this theory for the first time by analyzing genetic variation in the TREX1 gene and active retroelements, and look for evidence that each has influenced the evolution of the other,” Malik said.