An archbishop and four Bushmen walk into a lab. What emerges is no joke, but a more complete picture of human genetic diversity than ever seen before.
This new study of five Africans has identified more than 1.3 million new human genetic variants and could contribute to a better understanding of the genetic underpinnings of human diseases. The data might also help drug companies devise more effective medications to treat diseases in Africa, where many drugs do not work as well as they do in people of European ancestry, who were the primary test subjects in designing the drugs.
Archbishop Desmond Tutu and four Bushmen community leaders from Namibia contributed their DNA for the new study, published in the Feb. 18 Nature. Researchers decoded the complete genetic blueprint of Tutu, who represents the Bantu ethnic group, and of one of the Bushmen, a man named !Gubi (punctuation characters in Bushmen names represent click consonants). The international team of scientists also deciphered the protein-coding portions of the genomes from three other Bushmen, G/aq’o, D#kgao and !Aî.
Analyses of the men’s genomes confirm that the Bushmen, also known as San or Khoisan, are among the most genetically diverse people in the world. Two Bushmen who live within walking distance of each other might have more genetic differences between them than a European and an Asian, says Stephan Schuster, a geneticist at Pennsylvania State University and one of the project’s leaders. The researchers found that !Gubi and Tutu each have about 1 million previously unseen variations in their genome. These variations, called SNPs, change a single nucleotide, or chemical building block of DNA. The two men differ in about 4 million SNPs, while 3 million SNPs separate J. Craig Venter and James Watson, both scientists of European descent who have had their own genetic instruction books decoded.
African populations have not been well represented in previous genomic studies, says Sarah Tishkoff, a human geneticist at the University of Pennsylvania in Philadelphia who was not involved in the new study. Until now, only one African genome – the genetic makeup of a person from the Yoruba ethnic group – had been completed. This new study “is going to set the stage for future studies in Africa,” Tishkoff says.
The new research also reveals evidence of mixture between hunter-gatherer Bushmen and agricultural Bantu people. Tutu has a female heritage marker usually found only in Bushmen, indicating that the archbishop had a female Bushman ancestor. And one of the Bushmen has a type of Y chromosome often found in Bantu men, indicating a Bantu male ancestor.
The new study could help scientists assess whether genetic variants found in other research are really linked to diseases, Schuster says. “We can kill the noise in the disease database,” he says.
For instance, a genetic variant in the LIPA gene has previously been associated with a fatal lipid metabolism disorder called Wolman syndrome. But three of the Bushmen carry the variant and are still in good health at more than 80 years old, possibly indicating that the change is not disease-causing or that other genetic variants might counteract the Wolman variant.
Large amounts of genetic variation are good for our species, Schuster says. The new study “really shows why humans are such a hardy bunch, because we are lucky to have such a huge diversity underpinning our genome.”