Some of the Bushmen coding alleles have been associated with disease. The results of the present study may help to reevaluate these earlier reports. They may also help to identify potential population-specific incompatibilities of drugs that are prescribed globally. Furthermore, the results of this study have implications of admixtures that may be determined from further research. Population-wide PCA defines the Bushmen as distinct from the Niger-Congo populations as from Europeans. Within-Africa analysis separates the Bushmen from the divergent western and southern population, although ABT is within the southern Bantu cluster. However, variable relatedness of the Xhosa to Yoruba may suggest past admixture and/or historical diversity within this population. Within the Bushmen group, the authors predict that the Ju/' admixture and HGDP are essentially the same population. Divergence of KB1 and MD8 may be explained by recent Bantu admixture or by unique sub-populations with a small percentage of ancient Bantu admixture. But patterns of migrations must wait for a detailed population-structure analysis based on novel-content arrays that include the 1.3 million new genetic markers from this study.

Since the Bushmen hunter-gatherers have never adopted agricultural practices, the sequence variants found in their genomes may reflect an ancient adaptation to a foraging lifestyle. With Kalahari Bushmen, adaptation to arid climates also occurred, since several phenotypic traits have been noted that are absent in other human groups, such as the ability to store water and lipid metabolites in body tissues. These physiological and genetic differences may guide future studies into the question of whether population replacement, rather than cultural exchange, has driven the expansion of agriculture in the southern regions of Africa as happened with the late Stone Age populations in Europe.

4.

The authors state that the presence of SNPs that were observed in Bushmen and the phenotypes that were previously observed can lead to testable hypotheses. However, these are to be considered only candidates for the functions suggested; experimental tests must be...

Some of them can be related to the Bushmen lifestyle, such as the European -- derived lactase persistence allele and the lack of the allele associated with light skin color. Another example is the lack of the African-specific malaria-resistance allele. The lack of this allele in the Bushman populations might have terrible consequences on the already-deminished population of well-adapted foragers when they are forced into a farming lifestyle that brings increased pathogens. These genetic markers may enable the rate of human adaptation in changing environments to be traced.
The study uncovered many other interesting SNPs, including one that affects the taste receptor gene that provides the ability to taste a bitter compound; this may reflect a need in hunter-gatherers to avoid toxic plants.

One author advises being skeptical about the validity of untested populations, however. The point is illustrated in the Supplementary materials, in a case concerning the Lipo gene, which is annotated in a public database associated with Wolman's syndrome.

5. The results of Figure 2 are consistent with the view that southern Africans are among the most divergent human population. In the left panel, Figure 2 compares SNPs from KBI with those of Yoraban NA19240 and ABT; in the right panel, SNPs from KBI are compared with those of an American with European descent, J.C. Venter, and a Chinese individual. More SNPs were found in subject KBI than have been reported in other individual human genomes. This was also true for ABT, although his numbers were lightly lower. Some of the variation in SNP numbers may be due to differences in technology and levels of coverage. However, the number of novel SNPs (not previously seen in other individuals) is much higher for KBI and ABT than for other individual whole genomes. KBI and ABT each have about 1.3 million SNPs not shared with each other or with the published Yoruban, Asian, or Euopean complete genomes.