By Thomas H. Maugh II
February 18, 2010

Scientists have long known that natives of southern Africa are genetically quite distinct from people in the rest of the world, but a new study in which the genomes of four African Bushmen and one Bantu were sequenced or partially sequenced indicates that there is a much greater diversity among the populations there than had previously been suspected.

Two Bushmen from different tribes living within walking distance of each other can have greater genetic differences than a European and an Asian, according to the study published in Thursday's edition of the journal Nature.

"If we really want to understand human diversity, we need to go to Africa and study those people," geneticist and lead author Stephan Schuster of Pennsylvania State University said in a teleconference Wednesday.

The study, which marked the first time that the DNA of a hunter-gatherer had been sequenced, found about 1.3 million novel variants in the genetic sequences, accounting for about 1% of the total human genome, the researchers said.

The greater genetic diversity there, researchers said, probably results from the fact that modern southern Africans originated there and have lived continuously in one region much longer than other peoples, thereby having more time to accumulate variations. Despite those differences, the Bushmen also had similarities that distinguish them from other population groups. They were missing a gene that allows them to metabolize lactose; were lacking a gene that promotes malaria resistance; had genes that gave them denser bones, greater strength and a greater ability to run short distances; and had another gene that promotes their ability to retain salt and water at high temperatures.

Even so, the researchers said, it is important to remember that the overall genomes of all human beings are virtually identical and the small differences they observed represent adaptations to new or changing environments.

The research was conducted by a team headed by Schuster and geneticist Vanessa M. Hayes of Children's Cancer Institute Australia in Sydney. They completely sequenced the genomes of one Bushman and one Bantu and sequenced the protein coding regions of three other Bushmen.

The Bantu was Archbishop Desmond Tutu, who served as a surrogate for the agricultural peoples who account for about 80% of southern Africa's population. The four Bushmen, also known as Khoisan or San, were the heads of their tribes living in the Kalahari Desert. Their names were !Gubi, G/aq'o, D#kgao and !Ai and they spoke Tuu, Ju/'hoansi and !Kung. (The unusual characters denote clicking sounds in the languages.) One immediate surprise to emerge from the research, at least for Tutu, was that one woman in his lineage was of Bushman origin. It is not clear, however, how many generations back that woman lived.

The greater strength and sprinting ability of the Bushmen would be a clear advantage for survival in the arid Kalahari, as would the ability to retain water and salt. The lactose intolerance and lack of resistance to malaria, however, could be significant problems as more of the Bushmen are forced into agrarian societies where milk is a staple and the density of malaria-bearing mosquitoes is much higher than in the desert.

All of the genomes are being placed in online databases, where they will be freely available to other researchers. The medical histories of the subjects, all of whom are in their 70s and 80s, will also be posted to help researchers link specific gene variations to diseases.

None of the Bushmen had any previously known genetic disorders. Tutu is a survivor of polio, tuberculosis and prostate cancer.

The southern Africans join a small select group of people who have had their entire genomes sequenced, including Nobel laureate James Watson, pioneering geneticist Craig Venter and anonymous Chinese and Korean men.

The fact that the team was able to sequence five separate genomes illustrates how far the technology has come in recent years. The original Human Genome Project took more than a decade, involved thousands of researchers and cost an estimated $3 billion. The Africa project took about a month to sequence each genome and the total cost was $2 million, Schuster said.


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