Graphic by Sergey Nivens, Shutterstock.
Stanford Medicine Scope - May 18th, 2017 - by Bruce Goldman
Leprosy begins with a bacterial infection and, after five to 20 symptom-free years, can end in severe nerve, skin, vision and respiratory-tract damage and limb amputations. Treatable and in decline today, this scourge has plagued humanity for many thousands of years and still persists in Southeast Asia and India.
Modern human beings arrived in Southeast Asia around 50,000 years ago. It seems they brought leprosy with them, as evidenced by the high prevalence in that geographic corner of the world of a gene variant that appears to be protective against leprosy.
Genes can come in different versions. (Eye color is one easy-to-grasp example, but there are myriad more-subtle examples, too.) Over long enough evolutionary periods, as those with the gene version that works best in a given environment survive better and bear more viable offspring, one version may eventually become dominant in that environment: brown eyes in the tropics, blue eyes in the northern latitudes.
Of all our genes, the ones most prone to variation and rapid evolution are those involved in our immune system. This isn’t surprising, as defending ourselves against infectious disease has always been one of our species’ best ways to ensure a future for us, our progeny and their progeny.
In a new study published in Cell Reports, a team led by Stanford immune-genetics experts Hugo Hilton, DVM, PhD, and Peter Parham, PhD, examined a particular version of a gene encoding for an important cell-surface protein that’s a key player in our immune response. This gene version is found only in Southeast Asia (not counting individuals who’ve migrated elsewhere, or their descendants), where it’s the most common version in that region. It’s estimated to have arisen there just about the time we did and to have spread rapidly.
Hilton, Parham and their colleagues showed that this gene version is a leprosy specialist: Its cell-surface protein product is particularly good at binding to immune-system-triggering (“immunogenic”) molecules from Mycobacterium leprae, the bacterium that causes leprosy, and at presenting its molecular captives to immune cells that, alerted to the pathogen’s presence, wheel into action and kill the cell harboring the bacterium.
This laser focus on M. leprae-associated molecules has a downside: The gene version favored by evolution in what was once a heavily leprosy-burdened environment is not so good as some of its alternative versions at binding to immunogenic molecules that characterize malaria, Salmonella, HIV, a common variety of seasonal influenza called H1N1 or other infections. Individuals with this version are also predisposed to autoimmune disorders such as myasthenia gravis and Graves disease.
It’s a trade-off that once must have made very good sense and still comes in handy from time to time now. But in evolution, as in all of life, there’s no free lunch. You just have to hope the lunch you’ve got hits the spot.
