Researchers from Penn State University, the University of New South Wales in Australia, and the Baylor College of Medicine have sequenced the genomes of four individuals from different groups of the click-speaking San of southern Africa, as well as of Bishop Desmond Tutu of South Africa.  Their results, published online yesterday in the journal Nature, are providing striking new insights into human genetic diversity.

Joanna Mountain, 23andMe’s Senior Director of Research, has been studying the genetics of click-speaking peoples of Africa for over ten years.  Dr. Mountain said the new study “has demonstrated that any two San individuals are as genetically different from one another as a European and a Chinese individual. Clearly the linguistic diversity of the San is matched or even exceeded by their genetic diversity. Furthermore, even though the San Bushmen are often described, even by this study’s authors, as the ‘oldest known lineage of modern humans,’ the new genetic data reveal that the San have evolved genetically as much as any group, partly through the random mutations that occur over time, but also through changes that enabled them to handle their often challenging, exceedingly dry environment.”

Read more about this study:

• New York Times
• Technology Review
• Not Exactly Rocket Science

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A recent study led by Carlos Bustamante of Cornell and Sarah Tishkoff of the University of Pennsylvania has shown that genetically speaking, African American can mean a lot of different things.

The researchers and their co-workers analyzed DNA data from 365 African Americans, 203 West Africans from 12 different countries, and 400 Europeans from 42 countries.  Their results, published in the Proceedings of the National Academy of Sciences, show that the average amount of DNA in an African American’s genome that could be traced back to West Africa was about 77%, but ranged from as little as one percent to as much as 99%.

These findings have important implications not only for understanding the ancestry of African Americans and the history of human migrations, but also for medical treatment.

“That some individuals who self-identify as African American show almost no West African ancestry and others show almost complete West African ancestry has implications for pharmacogenomics studies and assessment of disease risk… caution should be used in prescribing treatment based on differential guidelines for African Americans, ” the authors write.

The researchers also undertook an analysis to determine if any particular stretches of DNA found in African Americans were more often descended from their West African ancestors.  The strongest finding was that there are elevated levels of African ancestry on the X chromosome, most likely reflecting a history in which interracial mating primarily happened between mothers with African ancestry and fathers with European ancestry.

The African groups studied by the research team represent just a few of the ten ethnicities mentioned most often in slave trade records. Future studies might examine other relevant populations from Sierra Leone, Senegal, Guinea Bissau, and Angola, providing further insights into the genetic ancestry of African Americans.

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In our last post we highlighted a few of the coolest (in our opinion!) health-related developments of 2009.  But human genetics isn’t all about disease.  Here are a few more favorites:

The Romanovs

2009 saw the identification of the remains of the missing members of this Russian royal family, as well as identification of the mutation that caused the hemophilia that plagued their youngest son.

Leaving No Stone Unturned: DNA Analysis Confirms Identities of Missing Romanovs

Researchers Discover the True Identity of the “Royal Disease”

The Celtic Fringe

The genetics of adorable little critters helped scientists understand the prehistory of the British Isles.

Life on the Fringe: Shrews and Voles Reveal Clues to British Prehistory

Link Between Australian Aborigines and India

Scientists discovered mitochondrial DNA markers shared by isolated tribes in India and native Australians…and nobody else.

Direct Genetic Link between Australia and India Provides New Insight into the Origins of Australian Aborigines

Largest Ever Study of Modern African Genetics

2,432 DNA samples from 113 diverse and distinct groups of people from across the African continent as well as 60 non-African groups. Everyone from the Mozabite Berbers of Morocco to the hunter-gatherer San of the Kalahari Desert, and many in between.

Scientists Publish Largest-Ever Study on the Genetics of Modern Africans

Dogs

We can’t forget all those dog genetics studies.  Man’s best friend is certainly a friend of the Spittoon’s!

Single Gene Responsible For Stubby Legs In Dogs

Whence Rover? Genetic Study Suggests Africa May Have Whelped Man’s Best Friend

Study Sniffs Out Genes Behind Doggy ‘Dos

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Malaria is one of the leading causes of death in the developing world, claiming nearly a million victims each year. The great majority of them are African children below the age of five. The illness is caused by a single-celled parasite called Plasmodium that is transmitted by mosquito bites to humans. In a paper published today in Nature Genetics, a group of African and British doctors and scientists report on their study of the genetic roots of malaria susceptibility. They found no new smoking gun with this effort, but learned much about how to improve African genetic studies in the future.

The researchers gathered the SNP genotypes of 2,500 children, with the consent of their parents, from a small region in The Gambia. About 1,000 of the children had been admitted to the hospital with a case of severe malaria — the other 1,500 were newborns. In a genomewide association study, the researchers checked each of a half-million SNPs (single nucleotide polymorphisms) for sharp differences in genetic composition between the group of children suffering from malaria and the group of newborns, who served as an approximation of a malaria-free group. If one version of an individual SNP was seen at high frequency among the malaria victims, but at low frequency in the newborns, then the difference might be because the SNP tends to cause malaria or is nearby one that does.

Upon scanning their data, the researchers came up more or less empty-handed: by the usual standards of the field, none of the 500,000 SNPs would pass muster.

This deflating result stands at odds with what is known already about the genetics of malaria susceptibility. Most people who have taken a biology class learn that human populations in malarial regions have developed a natural immunity to malaria infection, not through their immune systems, but through a genetic modification of hemoglobin. Hemoglobin is a molecule charged with ferrying oxygen from your lungs (and the lungs of most life forms that have them) to all your cells, an essential task. Biologists have traced hemoglobin-based malaria resistance to a change at a single DNA base pair on chromosome 11 — wouldn’t we expect at least this SNP to light up as significant?

In truth, the failure wasn’t so surprising; it arises from the interplay of genetics with our species’ history. Humans first arose in Africa, so that’s where genetic variation has had the longest time to build up. Modern-day Asian, European, and Native American people descend from people who emigrated from Africa about 50,000 years ago. These migrants carried just a subset of the African gene pool with them, so non-African populations today have much less “well-mixed” genomes than African populations. The present study uses genotyping chips developed for use in European populations, and its failure to find the known hemoglobin SNP (which isn’t even genotyped by the chip) and other known genetic contributors to malaria resistance is essentially due to the fact that you’d need more like two million SNPs than half a million to do the job right.

The solution, you’d think, is just to make a chip with a lot of markers for specific use in Africa, and be done with it. But the authors show that African genomes appear to be mixed so well that no single such chip could be designed. Instead, they propose an alternative approach: use a good but inevitably suboptimal African SNP chip in your full study sample, then obtain full genome sequences from a small number of the members of that sample. Then, using a powerful statistical method called imputation, you use the full sequences of the smaller group to fill in the full genomes of the entire study sample based on their SNP genotypes. This approach, as the authors demonstrate convincingly in the case of hemoglobin-based malaria resistance, would provide a statistically powerful and economically viable means of tracking down the causes of some of the most challenging health problems of our time.

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When scientific research is published, the authors often confess that they wish they’d collected more data. Critical reviews of research studies often say the same thing. Indeed, if there’s anything scientists love, it’s more data.

Which is why the members of an international team of genetic anthropologists led by Sarah Tishkoff of the University of Pennsylvania are probably quite pleased with themselves. In a new study published this week in Science, the team took the concept of “more is more” to heart by collecting and analyzing the DNA of thousands of people, mostly from Africa, so that they might uncover more clues to not only the genetic make-up of modern Africans, but also the genetic history of Africans and non-Africans alike.

The scientists’ first step was to collect DNA from a diverse set of Africans. Africa is the most culturally and linguistically diverse place on Earth, so it was important to take a wide sample of individuals from all corners of the continent. In total, they collected 2,432 DNA samples from 113 diverse and distinct groups of people from across the African continent as well as 60 non-African groups. They sampled everyone from the Mozabite Berbers of Morocco to the hunter-gatherer San of the Kalahari Desert, and many in between.

But the hard work didn’t stop there. The scientists then examined 1,327 genetic markers across the human genome for each individual studied. While many studies focus on a particular part of the genome such the mitochondrial DNA or the Y chromosome, this study took a comprehensive approach. Finally, the researchers used sophisticated statistical techniques, piecing together how these populations from Africa and around the world were the same, and how they were different.

The results confirmed that Africa has the highest genetic diversity of any continent, as many scientists have proposed. In fact, the authors found genetic diversity to decrease the further one traveled away from Africa. Genetic diversity is often used as a measure of how long ago humans inhabited a region — conventional wisdom places the earliest humans in East Africa, which had exceptionally high genetic diversity according to this study, though an analysis by the researchers put the origin of the human expansion farther south near the border of Namibia and Angola.

The study also shed light on the incredible genetic diversity among African populations, said Roy King, a professor of psychiatry and anthropological geneticist from Stanford University:

Not only did farming and pastoral communities differ from hunter-gatherers, but within the broad range of agricultural populations of West and West-Central Africa — from which many African Americans derive their ancestry — the authors also found some genetic diversity. For example, the Dogon of Mali, although geographically near the Mandinka of Senegal, cluster with North African Berber populations. Thus, this study supports the notion that not only is Africa varied in culture — art, music, religion and language — but also harbors a rich genetic diversity across its multitude of ethnic groups.

The authors also found a loose connection between the genetics of a population and its language. However, there were a few exceptions, most often the result of a population adopting a new language within the last few thousand years.

The sheer size and diversity of the DNA samples collected allowed the researchers to construct a human family tree based on their analyses. Not unexpectedly, the tree they constructed fits well with current theories on the genetic relationship between Africans and non-Africans; namely that all non-Africans are descended from a particular group or groups of people who were the first humans to migrate out of Africa tens of thousands of years ago.

This study is important for a multitude of reasons. It has been able to confirm theories from the archaeological, cultural, and linguistic records on the origins and movements of Africans and non-Africans.

“It fits nicely with earlier genetic studies, while subverting the early 20th century colonialist idea of sub-Saharan Africa as constituting a homogeneous genetic an cultural unit,” King said.

It also creates a new resource that historians, linguists, archaeologists and scientists from a range of other disciplines can use in their own work. If we are lucky, this study will bring forth a flurry of activity surrounding the origins and history of the African continent, and the people who live there.

Credit: istockphoto/Erie

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Africa is home to a number of dwindling hunter-gatherer populations, most of them living deep in the rainforests that stretch from western Africa’s Atlantic coast to the eastern edge of the Democratic Republic of Congo. Known as “Pygmies” because of their short stature, previous studies (including one funded by 23andMe) have shown that these forest-dwelling groups are descended from populations that arose 20,000 to 50,000 years ago.

But today populations such as the Mbuti, who live in the eastern forest, speak radically different languages from those spoken by the Biaka and other groups who live in the west. In fact, the Biaka speak a language belonging to the Niger-Congo linguistic family, which is associated with the expansion of agriculture throughout sub-Saharan Africa less than 5,000 years ago.

How did a hunter-gatherers in the African rainforest end up speaking less like their distant cousins and more like their farming neighbors? A paper published last month in Current Biology offers an explanation by genetically modeling the population history of the western African Pygmies and their farming neighbors using autosomal DNA, which is inherited from both parents.

Verdu and colleagues suggest that for most of the last 50,000 years western Pygmy groups were a single population, exchanging marriage partners and migrating through large tracts of the western forest. They also suggest that, contrary to earlier studies, the western African Pygmies were isolated from non-Pygmy populations until about 2,800 years ago, when they began exchanging marriage partners with neighboring farming populations.

Today, social taboos discourage Pygmy men from taking wives belonging to neighboring farming groups. But farming men and Pygmy women can marry, and sometimes the children of these unions sometimes return to their mother’s natal group in the forest. These cultural taboos and the resulting sex-biased gene flow probably began after western Africans invented farming techniques and began expanding through the rainforests about 5,000 years ago.

The research by Verdu and colleagues is the first to put a date on the breakdown of western Pygmy migration patterns due to the expansion of farmers — about 2,800 years ago. The integration of western Pygmy groups and farmers is also reflected in the linguistic similarity between the groups; both speak Niger-Congo languages. It is generally assumed that this linguistic shift occurred as farmers and hunter-gatherers intermarried.

The original languages of these western Pygmies have now been lost. But because Pygmy women have been marrying into farming groups for millennia, their genetic signature is well preserved in both populations. Using mitochondrial DNA, which is passed down from mother to child, genetic researchers discovered that over 80% of western Pygmies carried lineages derived from haplogroup L1c1a. About 20% of farmers from neighboring villages in western Africa carry the same haplogroup as evidence of their Pygmy maternal ancestry.

Could you have Pygmy ancestors? That’s difficult to say. About 12% of African Americans carry mitochondrial DNA lineages belonging to haplogroup L1c, which indicates maternal ancestry somewhere in the Congo basin and surrounding areas, but not Pygmy ancestry per se. Absent a confirmed assignment to L1c1a, the odds are that the maternal ancestry of an African American individual in haplogroup L1c traces back to farming rather than Pygmy populations.

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A Nilotic-speaking pastoralist from Tanzania / Sarah A. Tishkoff

Genes are just one component that children inherit from their parents. Throughout much of human history, especially when populations consisted of small hunter-gatherer groups, the language and lifestyle of a people were also inherited from generation to generation. This is why genetic patterns and cultural traits are often correlated. So, when scientists see cultural similarities between two populations, they can ask whether there are genetic similarities between the two groups as well. For many cultural traits, such as pastoralism and agriculture there is still a debate: did people actually migrate into new regions, bringing their genes and culture with them, or did the language and lifestyle simply spread by word of mouth to new lands?

In this week’s Proceedings of the National Academy of Sciences, scientists from Stanford University (several of whom are also associated with 23andMe, including myself) have used the principle of genetic and cultural exchange to find the first genetic evidence of a prehistoric migration of people from Tanzania to southern Africa. We discovered a mutation (aka ‘SNP’) on the Y-chromosome that originated about 10,000 years ago in eastern Africa and is now most common among people from two regions: Tanzania and southern Africa.

Pastoralists (people who rely heavily on animal husbandry for food) such as the Datog and Burunge of northern Tanzania carry the newly discovered SNP. In fact, it is present among 30-40% of men from these populations. Unexpectedly, the click-speaking Kxoe of southern Africa carry the same SNP at similar levels to the Tanzanian populations, indicating that these people are closely related to the Tanzanian pastoralists. The evidence indicates that men from southern and eastern Africa shared very recent common ancestors between about 1,200 and 2,700 years ago.

With this genetic evidence in hand, we then turned to archaeologists to see if the fossil record indicated an ancient migration around this time.

As it turns out, the current thinking among archaeologists is slightly different than what this new genetic evidence has revealed. Archaeologists currently favor a model in which the cultural practice of pastoralism spread from an unknown eastern African group into southern Africa about 2,000 years ago, perhaps without any sort of movement of people (i.e. genetic exchange). Our new genetic study, while still supporting the archaeological record for the timing and place of the origins of pastoralism in sub-Saharan Africa, puts a new twist on the current thinking. It suggests that a small group of men actually migrated into southern Africa about 2,000 years ago. These men probably married into local hunter-gatherer populations, contributing their livestock and cultural knowledge of pastoralism. These migrants were probably closely related to the modern day Datog and Burunge groups of Tanzania.

A shift to pastoralism was a fundamental change for the hunter-gatherers of southern Africa during the last couple thousand years. It caused a dramatic change in the culture and belief systems of these people. As pastoralism became more widespread in southern Africa, so did the beginnings of a sense of ownership of animals and the emergence of chieftans. These changes can still be seen today in the practices of people throughout Namibia, Botswana and South Africa. For example, the Nama of Namibia began practicing pastoralism not long after its arrival in southern Africa and continue to do so today.

The question of whether the shift from hunting and gathering to agriculture was the result of cultural exchange or actual migrations between groups is one of the most important debates among archaeologists and geneticists. With this new genetic evidence, we think we have answered this question, at least in southern Africa. Future studies will further examine the relationhip between genes and culture, and how this relationship has influenced the genetic and cultural makeup of modern African populations.

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