Genetic Structure of the Indigenous Hunter-Gatherer

Gene Following their abstract/introduction of their study, the authors described their selection of participants for their study of the genetic structure of the indigenous hunter-gatherer people of southern Africa. They based these choices for genome testing on the subject's linguistic group, the geographical location, and the Y-chromosome haplogroup representation. All the men were about 80 years old, from arid desert climates and geographically and within the distribution of the Khosian and Niger-Congo languages.

Four indigenous hunter-gatherers were from Namibia and the Kalahari Desert, and each was the oldest member of his community. Northern Kalahari is the origin of three of these men, and Southern Kalahari is the origin of the fourth. Their language was Khoisan, which includes clicks for additional consonants. In the study, the participants were named KBI, NBI, TKI, and MD8. The Bantu subject, called ABT, was Archbishop Desmond Tutu from South Africa, representing the Sotho-Tswana and Nguni speakers.

Tutu's Y chromosome was determined by genotyping and also by sequencing data from this study. Because they expected the genomes of the subjects to diverge more from the human reference than from the publically-accessible genomes, the researchers tried to generate a genome sequence that would be of high-enough quality so it could be compared with both the human reference and de novo assembly. To achieve this, they sequenced the genome of each subject to high coverage, the sequence data were validated.

Using the Phusion assembler, they created a de novo assembly. The authors described their methods briefly and provided a Methods Summary. The article focused on their findings. All details are available in Supplementary Tables and Supplementary Information that are referenced in their article in Nature. This style is suitable for a magazine like Nature, which publishes research in the natural sciences, including evolutionary biology, materials science, nanotechnology, genetics, and cancer research.

It is read by scientists of many disciplines, who would be interested in the facts of studies on other disciplines, but would not be interested in the underlying statistics and details. 2. Single-nucleotide differences from the human reference genome assembly, or SNPs, were identified for the five southern African genomes and compared with those from eight available personal genomes. Here, the SNP does not include changes to a base, and there are no restrictions on the allele frequency in a population.

The large number of novel SNPs found in the study invites the question of whether the current genotyping arrays are able to capture the actual extent of genetic diversity and the haplotype structure of the hunter-gatherers in southern Africa. When researchers used current-content Illumina rays to assess the percentage heterozygosity for over 1 million autosomal SNPs, they found that subject KBI had lower heterozygosity than a European control subject in a matched region. This was a surprise because genetic diversity is highest in Africa.

But an analysis of whole-genome sequencing data for participants KBI and ABT showed the expected high percentages of heterozygous SNPs. For KB1 it was 59% and it was 60% for ABT. This discrepancy reinforces the presumption that current SNP arrays for analyzing the southern African population are not adequate. 3. The authors observed a genome-wide trend for elevated SNP levels in promoter regions. Promoter regulatory elements tend to be enriched near nucleosome borders. The authors observed peak SNP levels there, particularly in the composite Bushmen genomes.

This increased SNP frequency in these Bushmen regions could drive phenotypic changes in humans. The 1.3 million amino acid SNPs reported in this study will be a good resource for future work and provide many new possible sites that have not been included in whole-genome association studies as yet. About 25% of these SNPs may turn up more information through computational methods.

The Gene Ontology categories that are represented in genes with one or more novel Bushmen (excluding those genes unique to ABT) include several functions that are known to evolve quickly in humans. Examples are immune response, reproduction, and sensory perception. Since all five participants are in old age (about 80) and are in good health, the novel coding variants of this study can be correlated with health status and phenotypes over the entire human life span.

The Bushmen reached advanced age despite living under harsh conditions caused by periodic famine and untreated illness. 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 conducted to investigate them further to determine their validity. Of the considerable number of amino-acid SNPs, a small number were found in databases that supply associations or other phenotypic information. 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.