Analyzing the genomic structure of five men descended from the hunter-gatherers of southern Africa – including famed South African Bishop Desmond Tutu – reveals surprising ways in which the genetic codes of these groups differ from others in the world and from each other, said a consortium of experts including those from Baylor College of Medicine in a report that appears today in the journal Nature.

In the report, the group describes the fully sequenced genomes of an individual descended from a hunter-gatherer society in the Kalahari Desert and Archbishop Tutu, a Bantu from southern Africa. They also describe the genomic protein coding regions of the genetic codes of three others from various areas of the Kalahari.

"These genomes represent an important advance in understanding human diversity," said Dr. Richard A. Gibbs, director of the Baylor Human Genome Sequencing Center and a senior author of the report. "We would like to thank Archbishop Tutu and the other four individuals for taking part in this work and for furthering our understanding of these important issues."

Dr. Stephan C. Schuster, professor of biochemistry and molecular biology, and Dr. Webb C. Miller, professor of biology and computer science and engineering, both at Pennsylvania State University, and Dr. Vanessa M. Hayes, group leader of cancer genetics at the Children's Cancer Institute Australia at the University of New South Wales in Sydney and a Fulbright Professional Scholar at Penn State, took the lead on the work.

"The Baylor Human Genome Sequencing Center's role was to generate the actual sequence of Dr. Tutu, using recently developed whole genome approaches," Gibbs said. However, he said that the findings give new clues about how the genetic sequences differ among populations.

For example, the gene differences among these five African individuals drawn from different geographic and ethnic populations are greater than those seen between a European and an Asian.

Some variations seem related to location, way of life

The researchers also found more single nucleotide polymorphisms (single base changes in gene sequences) in the fully sequenced genomes of one Kalahari Desert individual and to a less extent, in Archbishop Tutu, than has been reported in other individual genomes. Both also had a far higher number of novel single nucleotide polymorphisms than had been seen in other individual genomes that have been published. (BCM participated in the sequencing of the first individual genome - that of Dr. James Watson, the Nobel Laureate who first described the helical structure of DNA and led the initial human genome sequencing effort.)

Some of the differences in genetic code are related to lifestyle, such as lack of the gene for lactase persistence related to the ability to digest milk and an allele related to light-colored skin. They also found that the individuals lack a malaria-resistance gene, which may have ramifications for populations forced into an agrarian life in which mosquitoes play an important role.

"Therefore, these genetic markers may allow for the tracing of the rate of human adaptation in changing environments," the researchers wrote.

They also found single nucleotide polymorphisms related to enhanced physical prowess. For example, four had two copies of a gene associated with higher bone mineral density and strength. Three had two copies of a gene associated with increased sprint and power performance. One desert dweller had a gene for a chloride channel (a tiny pore in the cell membrane that allows ions in and out) that enables the person to retain salt and water – an advantage to people in dry climates.

The Bushmen of the Kalahari have remained hunter-gatherers, and their genes may reflect an adaptation to this lifestyle, the authors note.

Possible clues to spread of agriculture

"These physiological and genetic differences may guide future studies into the much debated question of whether population replacement, rather than cultural exchange, has driven the expansion of agriculture in the southern regions of Africa, as was observed for late Stone Age Populations in Europe," they write.

Others from the BCM Human Genome Sequencing Center who took part include Donna Muzny, Dr. Jeffrey G. Reid and Lynne V. Nazareth. Other institutions involved include Pennsylvania State University; Children's Cancer Institute Australia at the University of New South Wales in Sydney; University of Washington in Seattle; Roche Diagnostics Corporation in Indianapolis; Harvard Medical School in Boston; University of New South Wales in Randwick, Australia; Cornell University in Ithaca, N.Y.; researchers in Namibia; the University of Limpopo, Turfloop Campus, Sovenga, South Africa; Washington University in St. Louis, Mo.; Broad Institute of MIT, Cambridge, Mass.; the Sperling Foundation in Eugene, Ore.; the National Human Genome Research Institute in Bethesda, Md.

Funding for this work came from Pennsylvania State University, Roche Applied Sciences, Applied Biosystems, the Cancer Institute of New South Wales, Hyperion Asset Management Australia, the National Human Genome Research Institute, the National Science Foundation, the National Institutes of Health and the Gordon and Betty Moore Foundation.

Gibbs is the Wofford Cain Professor of Molecular and Human Genetics.