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Team Uses SNP Chips to Map Evolutionary History of Indigenous African Populations

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This article was originally posted on Sept. 21

Array-based SNP genotyping analysis has enabled an international team of researchers to unravel the genetic history of different population groups in southern Africa.

As part of the same study, the researchers claim they were also able to identify genetic traits associated with these groups' divergence from each other.

The findings were published online in Science this week.

Led by evolutionary biologists at the University of Uppsala in Sweden and the University of Witwatersrand in Johannesburg, the team used Illumina HumanOmni2.5 BeadChips to genotype 220 individuals from 11 different populations.

Based on the SNP array results followed by data analysis, the researchers were able to identify what they claim is the oldest divergence event in human history. Additional statistical analysis did not localize the origin of modern humans to a single geographic region in Africa, but instead suggested a complex population history within the continent.

"We raise the possibility that modern humans emerged from a structured population, in contrast to emerging from a homogenous and possibly small population," said corresponding author Mattias Jakobsson.

Jakobsson told BioArray News that it is often suggested that early humans originated from a small, localized population in eastern or southern Africa. But according to his team's findings, the human population has actually been structured into different subpopulations "for a long time" and "it is possible that modern humans emerged from a non-homogeneous group."

Jakobsson's team's research focused on two ethnic groups indigenous to southern Africa, the Khoi and San, that share physical and linguistic characteristics and are commonly grouped together under the name "Khoisan" to distinguish them from the Bantu-speaking majority of the region. The Khoisan populations are concentrated in arid parts of the region, especially in South Africa's Kalahari Desert, and previous studies have shown that the groups are genetically diverse, and appear to have descended from a deeply divergent human lineage.

After genotyping representatives from different Khoisan groups as well as other groups found in southern and eastern Africa, the researchers used a data analysis approach to create a genetic history of the African population.

According to Jakobsson, the team used a method which relies on random sampling of copy number variants, and has the "advantage of avoiding the effect of genetic drift within populations that could potentially affect other inference methods based on population samples, such as neighbor-joining trees based on pairwise genetic distance between populations."

As the history of sub-Saharan Africa does not conform to a simple tree-like model, Jakobsson said the group's approach was designed to capture the major flow of ancestry over time, he said. Ultimately, the group was able to use a mathematical model to estimate population divergence times.

Based on these analyses, the team concluded that Khoisan populations diverged from the rest of early human populations more than 100,000 years ago, before the migration of modern humans out of Africa, which is estimated by some to have occurred about 70,000 years ago. This event also predated the divergence of central African Pygmies from other African groups, the next lineage to diverge about 50,000 years ago.

In addition, the team found stratification among Khoisan groups. For example, the researchers estimated that the San populations from northern Namibia and Angola separated from the Khoi and San populations living in South Africa between 25,000 and 40,000 years ago.

An 'Economic' Approach

All of these results were obtained using SNP chips, a technology used by other researchers studying human origins.

For instance, Vanessa Hayes, a professor of genomic medicine at the J. Craig Venter Institute in San Diego, told BioArray News in June that she also uses SNP arrays to study indigenous populations in southern Africa. Hayes said she uses arrays to identify individuals for sequencing. As Hayes is involved in mapping the relationships between isolated groups, such as the Khoisan, she said she needs to be sure that an individual who claims to be from a certain group is actually genetically representative of the population in question (BAN 6/19/2012).

Affymetrix launched its Axiom Human Origins Array last year explicitly for use in such studies. The company designed the chip in cooperation with David Reich, an associate professor of genetics at Harvard Medical School. The company said at the time that one of the main reasons for launching the array was that most whole-genome genotyping chips were optimized for medical genomics projects and are not optimal for population genetics studies (BAN 11/1/2011).

Jakobsson said that his team used Illumina's catalog Omni2.5 BeadChip, but that it did "clean out a number of SNPs" in its quality control process, "as well as leave out the X chromosome" in its analysis.

One reason that SNP chips, rather than high-throughput sequencing, are being used in such studies is economic, Jakobsson said.

"You simply can interrogate larger sample sizes for the same money if you go for chips," he said. In terms of coverage, he noted that the latest SNP chips" include 5 million SNPs and capture more and more variants," adding that "good reference data" has been generated on SNP array platforms, "so that one can compare new data to published data from other populations."

Still, he said that the "ultimate goal" of evolutionary biologists will be to generate complete genomes of individuals, "ideally [with] single-chromosome reads to solve phasing issues."

While some have claimed that the absence of SNP chips with optimized content for evolutionary biology studies in sub-Saharan African populations has been a roadblock for the expansion of such efforts, Jakobsson said that another limitation has been access to samples.

"It has simply been more difficult to collect samples due to the varying levels of infrastructure and remote areas populated by some groups," said Jakobsson. "That genetic diversity within Africa is substantially larger than any other geographic region also adds to the issue since one has to include a larger number of populations to cover the continent," he said.

Ancient Adaptations

The team's SNP array analysis also provided glimpses into genes that showed natural selection prior to the split between the Khoisan and other populations 100,000 years ago, and allowed them to hypothesize about ancient relationships between African populations.

"Among the strongest candidates were genes involved in skeletal development that may have been crucial in determining the characteristics of anatomically modern humans," Jakobsson said.

Additionally, the researchers found that there was evidence for selection in genes involved in muscle function, immune response, and UV-light protection in local Khoe and San groups. Jakobsson said these could be traits linked with adaptations to the challenging environments to which the ancestors of present-day Khoisan populations were exposed that have been retained in the gene pool of local groups.

In terms of ancient relationships between population groups, Jakobsson and fellow researchers said their findings shed light on how pastoralism, the branch of agriculture concerned with the raising of livestock, first spread to southern Africa in combination with the Khoi culture.

In the paper, they said that archeological and ethnographic studies have suggested that pastoralism was introduced to the Khoi in southern Africa before the arrival of Bantu-speaking farmers, but that it has been unclear if this event had any genetic impact. As evidence, they noted that the Nama, a pastoralist Khoi group from Namibia, is similar genetically to southern hunter-gatherer San groups.

At the same time, they found that the Nama carry sequences in their genomes that are reminiscent of those found in East Africa's Maasai, a population located primarily in Tanzania and Kenya, hinting at historical mixing between these groups.
As this East African ancestry was absent or found at very low frequencies in the San populations, the study's authors suggested that mixing between ancestors of the Nama and the Maasai may have coincided with the introduction of pastoral practices to southern Africa.

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