Complete Khoisan and Bantu genomes

The number of published complete genomes is starting to grow exponentially it seems. Pretty soon, I'm guessing, once most major groups are covered by at least one individual, they will cease to be paper-worthy, and we will move on to the era of full-genome population studies.

One of the published individuals is Desmond Tutu, so I am adding this to the Famous DNA label as well.

From the paper:

In the 117 megabases (Mb) of sequenced exome-containing intervals, the average rate of nucleotide differences between a pair of the Bushmen was 1.2 per kilobase, compared to an average of 1.0 per kilobase differing between a European and Asian individual.

It's striking that two Bushmen are more different from each other than a European and an Asian are. This is in agreement with the idea that Bushmen have a substantial Palaeoafrican genomic component, while Eurasians and most other Africans emerged from a younger population flowering within the species, which I have termed "Afrasian". Eurasians are descended from these (presumably East African "Afrasians"), as are most Africans, but with varying degrees of intermixture with other (non-"Afrasian") groups of humans that lived in the continent from times immemorial at the time of the Out-of-Africa (and "Deeper-into-Africa") expansions.

From the paper, number of SNPs shared:

On the right we see some interesting facts for three individuals (Bushman, KB1; Chinese: YH; European-American: J.C. Venter). 2-way sharing between individuals is roughly in the order of ~500. The Bushman has twice as many "private" variation as the Eurasians, consistent with the ancient basal position in the human family.

From the paper:

The large number of novel SNPs raises concerns regarding the ability of current genotyping arrays to capture effectively the true extent of genetic diversity and haplotype structure represented in southern Africa. Assessing percentage heterozygosity for 1,105,569 autosomal SNPs using current-content Illumina arrays, we were surprised to find lower heterozygosity in KB1 compared to a region-matched European control (Supplementary Data and Supplementary Fig. 3a, b), because it is well known that genetic diversity is highest in Africa. However, analysis of whole-genome sequencing data for KB1 and ABT revealed high percentages of heterozygous SNPs (59% and 60%, respectively), as expected. This discrepancy underscores the inadequacy of current SNP arrays for analysing southern African populations.

This is not very surprising: SNPs used in microarrays have not been discovered in Bushmen, so by testing for heterozygosity in Bushmen using them, you actually underestimate it. By not including Bushmen in the SNP-discovery process you implicitly assume non-variability (hence "no SNP") at sites where Bushmen (but not other humans) are variable.

With whole-genome sequencing we are able to see that Bushmen are indeed highly heterozygous. This should serve as a warning for making too much of patterns of heterozygosity from microarray genotype data, even the latest ~1M ones.

The PCA is also interesting as it points out the familiar differentiation between Europeans-African farmers-Bushmen at the top and Bushmen-West-South Africans at the bottom):

NB: The paper is freely available to non-subscribers, so you can go ahead and read it in full.

Nature doi:10.1038/nature08795

Complete Khoisan and Bantu genomes from southern Africa

Stephan C. Schuster et al.

Abstract

The genetic structure of the indigenous hunter-gatherer peoples of southern Africa, the oldest known lineage of modern human, is important for understanding human diversity. Studies based on mitochondrial1 and small sets of nuclear markers2 have shown that these hunter-gatherers, known as Khoisan, San, or Bushmen, are genetically divergent from other humans1, 3. However, until now, fully sequenced human genomes have been limited to recently diverged populations4, 5, 6, 7, 8. Here we present the complete genome sequences of an indigenous hunter-gatherer from the Kalahari Desert and a Bantu from southern Africa, as well as protein-coding regions from an additional three hunter-gatherers from disparate regions of the Kalahari. We characterize the extent of whole-genome and exome diversity among the five men, reporting 1.3 million novel DNA differences genome-wide, including 13,146 novel amino acid variants. In terms of nucleotide substitutions, the Bushmen seem to be, on average, more different from each other than, for example, a European and an Asian. Observed genomic differences between the hunter-gatherers and others may help to pinpoint genetic adaptations to an agricultural lifestyle. Adding the described variants to current databases will facilitate inclusion of southern Africans in medical research efforts, particularly when family and medical histories can be correlated with genome-wide data.

Link