A gene variation in the immunity genes of the Khoe-San people increases their chance of having successful pregnancies and healthy babies. The gene variant is not found in any other people on Earth, suggesting there are drawbacks that have prevented its spread. In addition to possibly offering leads to making pregnancies easier, the discovery could improve the prospects for organ transplants.
The Khoe-San people are famous for their “click languages,” which provide them with more consonants than any other peoples on Earth. Incredibly, their genes show even more diversity than their phonemes, a result of living in the cradle of humanity and preserving gene variations left behind during the great waves of human migration. Despite this, relatively little research has gone into Khoe-San genetics.
“Only a handful of studies have investigated the function of immune genes in African populations," said Peter Parham, a professor at Stanford Univeristy and senior author of the paper in PloS Genetics. "As a result, we have probably greatly underestimated the breadth of human immune variation.”
Parham and his colleagues looked at genes controlling killer cell function. “We identified two recently evolved, novel gene variants that have unusual function,” they report.
These killer cells attack anything in the body they identify as foreign. The body uses HLA proteins on the surface of its other cells to enable the killer cells to recognize what should be left in peace. Organ transplants depend on either damping down the cells' ferocity or obtaining organs from people whose HLAs are similar enough to the recipient's to fool the killer cells.
Pregnancy presents the body with a unique problem. If the father has, but the mother lacks, genes for the HLA C2 protein, the combination can spell danger. The mother's immune system may attack cells bearing these HLAs, leading to malformed placentas that starve the fetus of blood and to more miscarriages, low birthweight babies and dangerously high blood pressure in the mother during the later stages of pregnancy. The Khoe-San have the world's highest rates of HLA C2 genes, making this combination particularly likely.
One of the Khoe-San alleles Parham identified avoids binding to HLA C2s, focusing instead on HLA C1s. The other allele produces a nonfunctional receptor that fails to bind to any HLA at all. The consequence is that babies are more likely to be born healthy, and mothers are at less risk during pregnancy. However, there may be a price to pay, with the immune system having less capacity to recognize foreign bodies and therefore fight infections.
As well as shedding light on the immune system, the first allele is exceptional in the way it redirects the gene's function to something quite different from other versions, rather than just modifying it.