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November 28, 2018

Welcome to our brave new 21st century

Filed under: Crispr,Genetic Engineering,Genetics,science — Razib Khan @ 4:44 pm

Sometimes you know something is going to happen. But you don’t know when it’s going to happen. It’s inevitable, but you don’t know when that inevitability is going to realize itself. In a way, death is like that for most of us.

And so it is with genetic engineering in the 21st century. This week MIT Technology Review broke the story that a researcher in China, He Jankui, used the CRISPR/Cas9 system to modify the genes of twin girls. His goal was to have them be were born with a deletion in the CCR5 gene, which would confer resistance to infection with HIV (about ~10% of Northern Europeans carry the deletion). These are the two first human beings born with genetic modifications that were directed by human beings.

Additionally, these are the first genetically modified human beings who will pass that modification to their children (unlike adults who might be targeted by genetic engineering, where their sex cells would not transmit the modification).

Humans have begun to direct their own evolution!

The science, or perhaps more precisely, the engineering, behind CRISPR/Cas9 is well outlined by this video:

There are many scientific and ethical details that go into the unpacking of the story of the gene edited children. But it is important to take a step back, evaluate the present, and consider prospects for the future. The CRISPR/Cas9 system for gene editing has been in use since 2012. In contrast, genetic engineering more broadly has been part of the scientific toolkit for nearly 50 years.

Asilomar, CA

In 1975 140 individuals from a range of disciplines came together in Asilomar, California, and agreed on rough guidelines for the use of the then-nascent technology of recombinant DNA.

This was the technology which brought the idea of genetic engineering to the public, with its first big success being the development of synthetic insulin, which has transformed the lives of millions of people who suffer from diabetes. The private sector biotechnology industry was birthed by the revolution triggered by recombinant DNA techniques in the second half of the 20th century.

For decades after 1975 genetic engineering occupied a prominent spot in science and popular culture. From genetically modified corn to transgenic mice, genetic engineering had widespread uses in both industrial and academic science.

So why is CRISPR/Cas9 such a big deal? In 2012 researchers realized that it was an efficient, cheap, and simple way to do genetic engineering (it had been known earlier as a peculiarity of bacterial defenses against viruses). In less than a decade, it has become even more effective as an editing tool.

In short, CRISPR/Cas9 democratized genetic engineering, so that small labs with few resources could perform experiments and trials. Previously, only laboratories with extensive experience and funding, or industrial scale corporations, could enter into genetic engineering projects. Within a few months, innumerable laboratories switched from other techniques of genetic engineering, which they had spent decades honing, to CRISPR/Cas9.

The nature of the transformation is obvious when you think about what has surfaced in the media in previous decades. One reason that you have heard about genetic engineering in the context of maize, “corn”, is that this is a crop with enormous economic implications. With older and more expensive technologies, genetic engineering could only be justified by a huge economic upside. Because of its cheapness and effectiveness, CRISPR/Cas9 methods have been applied to stem cells, plant and animal breeding, as well as public health. It may help in curing the most common form of muscular dystrophy, ushering in the era of curing of most Mendelian diseases.

Within the last six years, CRISPR/Cas9 has transformed whole sciences, opening up avenues of basic research which were previously not practical. Experimentation has taken over in the realm of experimentation! The plain truth of it is is that what happened in China may appeal to the love of the sensational, but it absolutely marginal to what CRISPR/Cas9 means to most scientists in their working life today. But, it reflects the fact that genetics is now an international discipline with hundreds of thousands of practitioners.

The times when 140 individuals could come together and agree on rules which industry and academia should follow, will follow, are likely long behind us. When scientists would talk about an “international consensus” in 1975, they meant North America, Western Europe, and Japan. Today that consensus has to extend to China, which is now the home to a great deal of cutting-edge biological science. But the cultural and social chasm between China and the developed world is large. And CRISPR/Cas9 is so simple and cheap that its use will likely spread to less developed countries, even less integrated into the community of science than China.

Though He, the researcher behind the “CRISPR babies”, may get the entry in Wikipedia he mentioned offhand to the media, the reality is that the scientific impact of his work is murky at best. Rather, his brazen contravention of the norms of international science presages the new era of the genetic engineering democracy, as the tools to modify the very stuff of life are now accessible to the many, rather than restricted to the few.

Interested in learning where your ancestors came from? Check out Regional Ancestry by Insitome to discover various regional migration stories and more!


Welcome to our brave new 21st century was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

November 21, 2018

The diverse tastes of the season

Filed under: Food,Genetics,science,thanksgiving — Razib Khan @ 1:31 pm

The holiday season is upon us. This means food, family, and fun. And when it comes to food and drink it often means excess. People gain weight during the holidays, and that’s a function of our calorie budget. There are some surpluses you don’t want.

But the process all starts with the senses. The visual allure of bright sweets and the enticing golden richness of meats. The tactile textures as we munch on foods with their own complex physical “form factor.” And of course there is smell and taste, two senses which are intimately connected, as anyone who has a severe cold can tell you.

For decades, one particular element of taste has been associated with the illustration of genetics for high school students: the strong bitter that some people experience when tasting paper soaked in phenylthiocarbamide (PTC). About ~75% of the population experiences a strong reaction when they put this paper to their tongue, and ~25% do not.

Recessive inheritance of the trait defined by shaded individuals

People who are “non-tasters” for bitter for PTC paper are recessive to those who are “tasters.” For genes, humans have two copies, and to be a non-taster individuals have to have two copies of the non-taster variant. For the ability to taste, you need only one copy.

The implication of the frequencies of the trait above and the inheritance pattern is that the underlying frequency of the genetic variants was similar. About half the gene copies in the population were non-taster, and half taster.

This was the theory. But until modern genomics, this could only be inferred. But today we know the gene and the marker within that gene that is responsible for this classical Mendelian trait. It is TAS2R38.

Here is a plot of three different genetic variations from a recent paper:

PAV = “taster” variant

One thing that is immediately evident from this map is that the ability to taste PTC is widely distributed, as is the ability to not taste PTC. There are some characteristics, such as light hair, which is found in only a few populations. In contrast, dark hair is found in most populations. What you see with PTC tasting is that variation is found across all populations.

What researchers have found is that these genetic variations are ancient, going back ~1,000,000 years, well before the emergence of modern humanity. The maintenance of this variation so long tells evolutionary biologists that both variants are useful in some fashion, and diversity is maintained within the human species.

Brussel Sprouts

It turns out that variation on TAS2R38 correlates with variation in bitter taste more generally, and that one’s sensitivity to bitter predicts phenomenon such as how much alcohol people drink, or how many vegetables children eat. What is happening is that people who are non-taster for PTC have reduced bitter sensitivity overall, and also have a lower aversion to bitter food and drink.

Because of the high genetic variation on this gene, there is going to be differences within families in terms of perception. Some research has suggested that mothers who are non-tasters who have children who are tasters report more conflict around food and that their children are particularly “picky.”

And so goes bitter, so with salt, sweet, sour, and even umami. All of these tastes that we take for granted have a biological basis that is genetically mediated. They are functionally important. In our evolutionary history bitters were often unpalatable or even toxic. This is primal, going back to the roots of the tetrapod lineages, as plants and animals have long engaged in an evolutionary arms race. Sour keys us into the acidity of foods around us. Salt is an important nutrient which was often in deficit in the ancestral environment, as were very sweet foods. Finally, umami signals that the foods we eat are rich in protein.

Lutefisk

But as omnivores, our environments are protean, as our species migrated across the face of the earth. Over the past ten years, as the complex genetic molecular genetic underpinning of variation in taste have been uncovered, a theme of diversity has been reiterated. The genes underlying variation in taste also impact other traits, and one can conceive of a model where human populations expand and must face dynamic trade-offs in particular characteristics. It’s not just about taste. One can imagine scenarios such that populations where a mix of individuals differ in taste perception are more fit than those populations which are genetically homogeneous.

However that diversity came about, it’s a fact of our life. On a social and cultural level, it results in the wide array of foods and cuisines that we as humans can enjoy. Our palette’s flexibility means that people from different cultures can and do enjoy each other’s cuisine.

The diversity even manifests within families. So this Thanksgiving while you’re observing someone wolfing down something that you’d never think of putting in your mouth, remember that we’re all different, and that’s because of our evolutionary history.

Check out Metabolism by Insitome and our other Insights!


The diverse tastes of the season was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

November 19, 2018

Have we seen the face of Rama?

Filed under: Population genetics,science — Razib Khan @ 11:29 pm


One of the problems with looking up pictures of the Kalash people of Pakistan is that photographers have a bias toward highlighting the most European-looking villagers. Let’s call this “Rudyard Kipling Lost White Races” syndrome. Therefore for your edification, I post the YouTube above which is probably more representative of what the Kalash look like.

The reason I post a link to what the Kalash look like is that it is germane to the answer to the question: what did the Indo-Aryans look like? The past tense is key since “Indo-Aryans” today means a lot of people in South Asia, in a literal sense.

In the post below Zach L. made a passing comment:

(1.) The AASI’s, which are sort of co-equivalent to the Negritos and Anadamese Islanders (one of the first coastal waves out of Africa that somehow also ended up in the Amazon). It’s interesting that they are substrate to every South Asian population (I think there are trace amounts in Central Asia, Afghanistan and even Iran).

(2.) the “Dravidian” farmers out of Iran. They are probably related to the J1/J2 types and might be an olive skinned population. Prominent in Sindh and Southern Pakistan through to South India (high % in Gujarat – must have been a locus of some sort).

(3.) our beloved Aryans who are especially prevalent among Brahmins, the Punjab and Haryana (though arguably the Haryanvis and East Punjab descend from Scythians to some extent). These look “European” but it’s a very different look to #2.

The Aryans are conventional European (light eyes, light hair, white skin) the ancient Dravidians would have (probably) looked like Middle Easterners (olive skin, dark hair dark eyes) and the AASI, ” looks like Papua New Guineans.

I can’t see any disagreement with point number two.

As for the AASI (“Ancient Ancestral South Indians”), we need to be careful here. They diverged from the ancestors of the people of Papua New Guinea ~40-50 thousand years ago. The divergence from the Andamanese, who probably migrated from mainland Southeast Asia, was not too much later. Aside from being very dark-skinned, the various extant “Australasian” people can be quite distinctive in appearance. The people of Papua, and native Australians, are quite robust. A substantial minority have blonde hair color due to a mutation common among Oceanians. The “Negrito” people of Southeast Asia and India all seem to be have adapted to a narrow relic niche, and may not be representative of their ancestors.

That being said, there is a particular non-West Eurasian look that many South Asians have which we can presume is the heritage of the AASI.

The comment about Aryans looking like Europeans raised my eyebrows a bit. This is a touchy subject, and to be honest my initial reaction was to be skeptical. But the more I read the primary literature to check up on Zach, the more reasonable this seemed to be. The dominant steppe signal into South Asia does resemble the people who were pushing into Central and Western Europe 1,000 years earlier than the Indo-Aryans, who were moving southward probably ~3,500 years ago. This is clear in rather simple statistical genetic analyses-populations such as the Kalash and Pathans for example show strong evidence of “European-like” gene flow.

Current work out of David Reich’s lab suggests that the Kalash are the best modern proxies we have for the “Ancestral North Indians,” the ANI. This population is modeled as:

– ~30% “steppe”, which is very similar to the ancestry which expaned westward into Europe between 3000 and 2500 BCE
– ~70% “Indus Periphery”, which seems the likely ancestral contribution of the people of the IVC, and is a heterogenous mix of Iranian-farmer and AASI

The mid-range estimate for the emergence of the Kalash mix is ~2,500 years before the present, but these usually have some downward bias, so it is reasonable that it would be greater than ~3,000 years. The samples from the Swat Valley dating to this period show gradual increase of “steppe” ancestry over time.

So one reason to be skeptical that the Indo-Aryans were “European-like” in appearance is that by the time they were flourishing in the lands previous inhabited by the IVC they may already have been more than 50% genetically like the people of the IVC. In which case, a minority would be very European-looking, but most would look vaguely West Asia, with some looking more stereotypically South Asian. If you look at the video above I think you do see the Kalash look this way.

One reason I’ve always been skeptical of the idea that the Indo-Aryans looked European, or, that their demographic impact was large, is that it seemed unlike both could be true. The expression of blue eyes among Indians was too low of a percentage.

Here is the frequency at a major SNP which predicts a lot of the blue vs. brown eye color.

What you see here is that the Kalash have the derived (“light”) variant at 25-30%. Notice that some Northern European populations are >75%.

Here are the frequencies from the 1000 Genomes:

I was a little surprise of the lack of variation from Punjabis (PJL), to Gujaratis (GIH), and Bangladeshis (BEB). Using the above logic the ~10% result would imply that a bit more than 10% European-like Indo-Aryan ancestry. This is reasonable.

But there are more SNPs than that that impact pigmentation. SLC24A5 is derived and fixed in Europeans, but pretty high frequency in South Asians (I have two homozygote derived copies and I’m rather brown). But some SNPs in SNP SLC45A2 are much more European specific in derived allele frequencies. So the 1000 Genomes surprised me somewhat:

Here you notice that the derived variant is nearly fixed in Northern Europe.  But in South Asian populations it’s not as high as you would expect. The frequency of OCA2 derived variant is higher than SLC45A2 in South Asia, while in Northern Europe it’s the opposite.

One explanation could be in situ selection in Northern Europe or in South Asia (or Central Asia). So these two markers suggest to me we can’t draw a straight line between physical affinity and total genetic ancestry/affinity.

 

November 15, 2018

The 20,000 year adventur eof the

Filed under: Genetics,History,science — Razib Khan @ 1:28 am

The great adventure of the Native Americans

Comanche warriors in 19th century Texas

In 1492 Christopher Columbus made definitive and lasting contact between Europe and the New World. This was not the first contact. We know for a fact that Greenland Norse knew of the New World as “Vineland.” They visited Labrador and Newfoundland to obtain resources, and in one instance, at L’Anse aux Meadows, attempted to settle permanently. But aside from sagas, nothing came of this.

It was for Columbus and the Europeans who came after to grapple with the fact that across the Atlantic there was a whole world unknown to them. Not Asia, but something fundamentally new. Peoples beyond their ken. In the five centuries since that contact, the engagement between these two worlds has defined much of the history of the world, as the displacement of the native peoples tracked the ascension of European peoples and their eventual conquest of the globe.

But in geological history, five hundred years is but a blink of an eye. The story of the native peoples of the New World, called Native Americans in the United States of America, First Nations, Aboriginal or indigenous elsewhere, begins over 30,000 years ago at the “top of the world.” The Asian landmass adjacent to the Arctic.

Citation: The population history of northeastern Siberia since the Pleistocene

Rather soon after modern humans break out of Africa ~50,000 years they began to expand all across Eurasia rapidly, absorbing groups like Neanderthals and Denisovans. One wave pushed north through the Caucasus and Central Asia and veered west, eventually giving rise to the various European hunter-gatherers of the Paleolithic and Mesolithic. Another group moved north and east, and gave rise a Siberian population, sometimes called “Ancient North Eurasians”, whose genetic shadow today spans Patagonia to Portugal.

But by ~25,000 years ago the appropriately named “Last Glacial Maximum” had commenced, and the habitable zones in Siberia shrank. These first Siberian populations retreated to the clement pockets available, and human habitation disappeared from much of the northern swaths of Eurasia.

A world of ice ~20,000 years ago
“This climatic change had major demographic consequences.”
Yakuts

Today most of the ancestry of people in Siberia does not descend from these Ancestral North Eurasians but from peoples related to the Han Chinese further to the south and east. While one group of African humans moved north rapidly ~50,000 years ago, another pushed eastward, through southern Asia, and onward toward the Pacific. Coming up from the south up through Manchuria as the climate warmed, these new Siberians eventually came to overwhelm the older populations. They contribute most of the ancestry of the Siberians of today.

But the genetic ghost of Ancient North Eurasians persisted as they were absorbed by other groups. This is how some of their ancestry can be found in many peoples to the west due to migrations out of the heart of Asia in the last 10,000 years. And yet another fragment of this people found itself far to the east, beyond the edge of modern Siberia, in a land now under the ocean in what is the Bering Sea. This was Beringia. A vast open tundra occupied by megafauna.

Further to the east were the vast ice sheets of North America, while to the west the rugged mountains of eastern Siberia, which were more frigid than they are today. But Beringia was not totally isolated. Sometime between 20,000 and 25,000 years ago, during the very heart of the Last Glacial Maximum, a group of hunter-gatherers migrated from the south and merged with a group of the older Siberian peoples.

Fused together, these became what we term “Beringians,” inhabitants of a lost subcontinent. About ~40% of the ancestry of the Beringians derived from the Ancient North Eurasians, and so connects them with people all across Eurasia, from Europe to India. No people in the world is predominantly Ancient North Eurasian today, but many people in the world are partly Ancient North Eurasian. The remaining ~60% of the ancestry of Beringians comes from a group of people who split from the ancestors of modern Chinese ~25,000 years ago. This is likely one reason that many anthropologists have long observed an affinity between Native Americans and the people of eastern Eurasia.

Modern Native Americans are overwhelmingly descendants of these ancient Beringians. Modern Native Americans are therefore ~40% Ancient North Eurasian, and 60% descended from a group of ancient East Asians.

This fusion likely occurred by ~20,000 years ago. But the archaeology seems to indicate that the native people of the New World did not begin to spread across the landscape of North and South America until ~15,000 years ago. The reason is simple: ice sheets blocked migration south and west. But by ~15,000 years ago we see evidence of humans as far as south as Chile! The movement seems to have been rapid and immediate.

One of the consequences of the period of isolation in Beringia is that the ancestral population of the Native Americans was relatively homogeneous, and went through what population geneticists term a “bottleneck.” When isolated populations remain small for many generations they lose much of their genetic variation by chance. And so it is that anyone who looks at the genetics of the peoples of the Americas notices that from north to south they are relatively similar to each other.

The rapid expansion from such a small population means that ancient DNA suggests that much of the genetic structure we see, differences between groups, have emerged only in the last 15,000 years. The thousands and thousands of languages of the indigenous peoples of these two continents are also the consequence of human cultural evolution over the last 15,000 years.

The native language families of North America

As these tribes diverged and separated, they began to develop their own distinctiveness through isolation. In some cases, population replacements and admixtures occurred. The latest evidence suggests that waves of people moved both north and south out of modern-day Mesoamerica in the last 10,000 years. Meanwhile, far to the north, populations continued to move out of northeastern Siberia well after the initial expansion phase and added to the palimpsest of peoples. The Na-Dene speaking groups of the western half of the United States and Canada seem distantly related to various Siberian tribes, and their linguistic unity and more noticeable East Asian appearance suggest a more recent history in the New World than those of the peoples to their south and east.

Surui elders of the Amazon

From the original unity has come a wide diversity. And yet there is one curious lacuna and perplexity: both ancient DNA and analyses of modern samples indicate that some tribes in the Amazon have a deep affinity with the hunter-gatherer tribes of Southeast Asia and the peoples of Papua New Guinea and Australia! And yet there is no signal of this ancestry in peoples to the north, ancient or modern.

Fundamentally, this is a deep mystery which no researchers have a good explanation for. And that goes to show that science can still present us with surprises that defy our expectations and to which we can present no good response.

The future will be filled with surprises, but the last 15,000 years of humans in the Americas have already been a great adventure.

Interested in learning where your ancestors came from? Check out Regional Ancestry by Insitome to discover various regional migration stories and more!


The 20,000 year adventur eof the was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

November 14, 2018

The Insight Show Notes — Season 2, Episode 7: the genetics of Native Americans

Filed under: Genetics,History,Native Americans,science — Razib Khan @ 7:34 pm

The Insight Show Notes — Season 2, Episode 7: the genetics of Native Americans

Ancient Beringians

This week on The Insight (Apple Podcasts and Stitcher) Razib Khan and Spencer Wells discuss the genetics and history of Native Americans, from the icy shores of the Arctic and to the frigid windswept plains of Patagonia, and all places in between. A 15,000 years story of migration and settlement.

Beringia

There was a lot of talk about Beringia. This is a region between Alaska and Siberia which is now under the ocean. But during the Last Glacial Maximum ~20,000 years ago when sea levels were lower it likely served as a refuge for Paleo-Siberians who retreated from other zones of northeast Asia. Once the climate warmed and the ice sheets opened up, about 15,000 years ago it seems that humans began to migrate southward.

A new preprint, The population history of northeastern Siberia since the Pleistocene, outlines the context of the emergence of the Beringian ancestors of modern Native Americans about 20,000 years ago. They were the fusion of two populations. One group was related to the people of modern East Asia, such as the Han Chinese. This group contributed about 60–70% of the ancestry to the Beringian population.

But the second population, sometimes termed “Ancient North Eurasians”, are very distantly related to the peoples of Europe. This group contributed to 30–40% of the ancestry to modern Native Americans, as well as 10–20% of the ancestry of Northern Europeans, and substantial fractions in parts of West and South Asia. See, 24,000-Year-Old Body Shows Kinship to Europeans and American Indians.

We alluded to the Beringian standstill hypothesis, that the Berengians were bottled up within their small corner of the world for many thousands of years. This is also connected to the small founding population of the New World.

Spencer discussed that haplogroup Q, the paternal lineage common in the New World, has a wide distribution in Eurasia. This could be the impact of the Ancient North Eurasians:

There was an extensive survey of the archaeology of the New World, and the Clovis First hypothesis. The Monte Verde site was mentioned as one of the primary ways in which Clovis First was refuted. Finally, we mentioned a paper in Nature that might push the occupation as far back as 130,000 years! (though most archaeologists dismiss it).

There was some reference to the Greenberg model of the classification of Amerind languages, as well as the Dené–Yeniseian family.

Much of the middle of the podcast focused on two papers that came out this week that filled in many details of the populating of the New World, one in Cell, and another in Science.

We talked about a 2015 result that indicated an Australasian population contributed some ancestry to people in the Amazon.

Interested in learning where your ancestors came from? Check out Regional Ancestry by Insitome to discover various regional migration stories and more!


The Insight Show Notes — Season 2, Episode 7: the genetics of Native Americans was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

October 17, 2018

The Insight Show Notes — Season 2, Episode 4: Finnish Genetics

Filed under: science — Razib Khan @ 11:02 am

The Insight Show Notes — Season 2, Episode 4: Finnish Genetics

Midsummer in Finland

This week on The Insight (Apple Podcasts, Stitcher and Google Play) we discussed the prehistory and genetics of the Uralic peoples, with a particular focus on the people of Finland, who are among their most numerous exemplars.

We mentioned that the Uralic languages have a northern distribution, extending from north-central Siberia to northern Europe.

See for yourself:

We mention two recent papers of interest:

We discussed the past 20 years of debate on the origin of the TAT-C/N1c Y chromosomal haplogroup. This male lineage is found at high frequencies all across the northern fringe of Eurasia, and in particular among Uralic populations.

Here is an early paper on the topic: Genetic relationships of Asians and Northern Europeans, revealed by Y-chromosomal DNA analysis. If you want to know the origin of the name “TAT-C”, listen to the podcast! Spencer tells you.

There was a lot of discussion about Uralic culture. For example Kalevala and blood sausage. The eastern Baltic was also one region where farmers from Anatolia never migrated. See The genetic prehistory of the Baltic Sea region.

Interested in learning where your ancestors came from? Check out Regional Ancestry by Insitome to discover various regional migration stories and more!


The Insight Show Notes — Season 2, Episode 4: Finnish Genetics was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

The expansion of the polar people

Filed under: Finland,History,science — Razib Khan @ 10:58 am

The expansion of the polar people

Sami in the far north of Europe

Since the development of agriculture 12,000 years ago, the cultural and genetic landscape of our world has been transformed by the emergence of peasants as the dominant demographic. For most of the recorded history, the average human was a peasant; a laboring tiller of the soil.

There were of course exceptions. Some peoples took up pastoralism. Others specialized in extracting resources from the sea — such as fisherman. And of course, there were hunter-gatherers who continued to practice a lifestyle as old as the human race itself.

Muskox in the Taimyr Peninsula

Though we often think of hunter-gatherers in a tropical context, the reality is that some of the most successful practitioners of this lifestyle have flourished in and around the Arctic. Not only have they flourished, but they have vastly expanded! For instance, the Thule culture of North America famously replaced the Norse agriculturalists of Greenland in the 15th century.

But perhaps the most speculator expansion of a non-agriculturalists in the north has been that of the Uralic peoples. A paper titled “Genes reveal traces of common recent demographic history for most of the Uralic-speaking populations” has an excellent map which illustrates the geographic span of this language family:

Citation: Tambets, Kristiina, et al. “Genes reveal traces of common recent demographic history for most of the Uralic-speaking populations.” Genome biology 19.1 (2018): 139.

Over twenty years ago researchers noted that one particular Y haplogroup lineage, N1c, was very common among Uralic peoples. Notice the overlap in distribution between this lineage and the Uralic populations below.

Distribution of N1c

The question then emerges: did the Uralic peoples come from the east, into northern Europe, or were they indigenous to northern Europe and expanded eastward? Examining patterns of genetic diversity indicate that this Y chromosomal lineage emerged in Siberia and later spread to northern Europe. Why? Because diversity accumulates in regions where the lineage has been present the longest.

Citation: Lamnidis, Thiseas Christos, et al. “Ancient Fennoscandian genomes reveal origin and spread of Siberian ancestry in Europe.” bioRxiv (2018): 285437.

New research from ancient DNA has clarified the timing of the arrival of these Siberians, Ancient Fennoscandian genomes reveal origin and spread of Siberian ancestry in Europe.

What we do know from modern genetic variation is that the Uralic people, including the Finns, seem to have recent Siberian affinities. In contrast, most other Northern Europeans do not have this — making it even more distinct. This Siberian affinity is strongest in the Sami hunter-gatherers of the far north.

Samples from a population in the Kola Peninsula of northern Russia from to 3,500 years ago yielded individuals who were even more Siberian than the Sami — as you can see in the admixture plot to the left. In particular, the Siberian ancestry of the Finnic people seems to be similar to that of the Ngananasn people of the Taymyr peninsula in Russia.

Looking at patterns within the genome of these ancient people, researchers have concluded that these people are the product of mixing between Siberians and indigenous European hunter-gatherers, which began to occur ~4,000 years ago. This aligns with other work that suggests that the Ceramic Comb Culture, the dominant Mesolithic hunter-gatherer society of northeast Europe before the expansion of agriculture, lacked Siberian ancestry.

Nenet Samoyed people

Where does this leave us? If we use genetics as a guide, it seems that around ~4,000 years ago a migration of Arctic hunter-gatherers swept out of the northern fringe of Siberia to the west. These people were likely related to the easternmost of modern Uralic peoples: the Samoyed tribes. The Y chromosomes of western Uralic peoples, such as the Sami and Finn, carry the hallmarks of ancestry similar to the Samoyeds. But the mitochondrial lineage is almost wholly similar to their European neighbors. Therefore, it seems that the spread of Uralic languages westward was due to the migration of males.

One of the implications of these conclusions is that the Uralic languages may have arrived in the Baltic after the Indo-European languages! In much of Estonia and southern Finland, the Corded Ware culture, presumed to be associated with Indo-Europeans, predates 2000 BC by centuries.

Though we often imagine that history and culture move in a singular direction, toward agriculture, the Uralic people may be an instance of an exception. If it is correct that hunter-gatherer Siberian men moved into large areas of northeastern Europe, and culturally assimilated more numerous peoples, some of whom were agriculturalists, it may indicate that the trajectory of history is more winding and complex than we may imagine.

Interested in learning where your ancestors came from? Check out Regional Ancestry by Insitome to discover various regional migration stories and more!


The expansion of the polar people was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

October 11, 2018

Why PCA and genetics are a match made in heaven

Filed under: Evolution,Genetics,science — Razib Khan @ 8:13 pm
Insitome customers and selected populations

The image above is not the work of a small child trying to sketch out a B-2 Stealth Bomber. Rather, it is a PCA plot, which shows the distribution of a subset of Insitome’s customers who have purchased the Regional Ancestry Insight — in terms of how they relate to each other genetically.

In green, I have added some British individuals, in red some Africans from Nigeria, and in blue individuals who are ethnically Chinese. The majority of our customers are of Northern European heritage, but a substantial minority are African-American or Asian-American and various mixes therein.

So why do we use Principal Components Analyses, PCA, in the first place? And how does it work to matches our intuitions about relatedness through abstruse mathematical formulae?

Why we use PCA in genetics

Real genetic varition…a little bit

Consider this slice of diversity to the left. Six individuals, top to bottom, genotyped on a small number of genetic positions, left to right. You should recognize the letters, as they are DNA base pairs, A, C, G, and T. You can see above that there are variations between the positions across individuals. Now imagine attempting to gain insight from looking at thousands of individuals (rows) across hundreds of thousands of markers (columns).

Raw genetic data is basically just a huge text file. When you are concerned with the variation on a single position, you can view from the results for individuals or populations in a table and expect most people to immediately understand the implications. Europeans who are lactose tolerant have a variant on a particular marker. If you are TT or CT you can digest milk sugar, lactose, as an adult. If you are CC, you can’t. There are only one a few things to keep track of: the person, and their genotype.

Representing variation on a single marker, a single variable, isn’t necessary because the human mind can process all that information. In contrast, lots of simultaneous variables are impossible to understand just by visually looking at a table. PCA is just one of many excellent ways to extracting signal out of the noise.

The plot to the left was generated from ~30,000 markers on a few hundred individuals from eight populations. This is not a large dataset today. The time it took to run the function which generated the raw PCA result output was the period between me pressing “enter” on the keyboard and me looking at the computer screen.

And yet despite the modesty of this dataset can you imagine me looking at 30,000 variables across 200 samples, and obtaining any understanding? Perhaps if I devoted my life to the project!

What about the math?

The way it works mathematically is that it takes the voluminous raw data, which is totally incomprehensible to the human mind and summarizes it into a set of independent equations — making it completely essential to the analytical toolkit. The data is actually a “matrix.” PCA transforms it with a series of distinct equations which can define the total variation of the underlying data.

A matrix of genotypes

These equations, or more properly dimensions, are arrayed in order of proportion of variation in the data explained. On a conventional PCA plot, you see the first two dimensions, which explain the largest and second largest proportion of the variation, as the x and y-axes. But there are many more dimensions you can break the data apart by, though quite often for genetic analysis the largest ones are sufficient to smoke out the population structure that you are interested in. The values of individuals in each dimension that drops out of the data can then be placed onto a coordinate system, which is much easier to digest than a table of raw variation.

The branching of human populations

But how can a mathematical framework make biological variation comprehensible through maps so well — especially with regards to genetic differences between populations? The answer to this is straightforward: human evolutionary history has a pattern, and that pattern leaves its stamp on the genome. PCA is just a pattern extraction method.

The raw material of variation are mutations, and the pattern of mutations in any human genome is defined by a pedigree back to common ancestors. People who tend to share common ancestors share mutations — and mutations are the raw material for the genetic variation that PCA summarizes.

When used in evolutionary genetics, PCA should ideally recapitulate the phylogenetic tree. Assuming that sample sizes are balanced, humans in worldwide datasets have the first principal component of variation, which invariably a dimension that separates Africans from non-Africans.

Why? Because this is the earliest separation between large lineages, and so this ‘separation’ has had the most time to accumulate distinct and unique mutations in their two respective lineages. The second dimension is usually one that defines the difference between people from the Eastern portion of Eurasia and those from the western portion of Eurasia. Again, this is an important phylogenetic distinction because these two groups seem to have diverged soon after their ancestors left Africa.

And so on. PCA is not the only way to visualize the data. If you run a computer program that counted up raw similarities and differences between individuals at each genetic position, you would notice that some individuals are more similar to others, some groups more similar to other groups, and this too would reflect the phylogenetic history. If you had more time and wanted to dig deeper, you could construct various models of population history, and see how well the data fit those models.

PCA is not the only way to understand genetic variation. PCA itself is not the genetic variation, but a way to represent that variation, but it is a fast method that starts with few assumptions and lends itself to easy graphical representation. It’s not coincidence that it remains popular to this day.

Interested in learning where your ancestors came from? Check out Regional Ancestry by Insitome to discover various regional migration stories and more!


Why PCA and genetics are a match made in heaven was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

September 26, 2018

India is eternal but Indians are not

Filed under: History,India,science — Razib Khan @ 10:18 pm

This week’s episode of The Insight dug deeply into the current scientific understanding of the genetic origins of the peoples of the Indian subcontinent. Recent publications and media coverage have caught the science in midstream, as scholars have to deal with the clamor for new information in the face of the need to be careful and cautious when presenting new results.

Steppe Chariot

The show notes linked extensively to the scientific literature which documents the interface between cutting-edge genomics, modern population genetics and computation, and finally the abstruse lab science of ancient DNA. Or, just go to the preprint, The Genomic Formation of South and Central Asia.

The general outline of what we know so far is straightforward. Over the past 10,000 years, the Indian subcontinent has been a great vortex, sucking in peoples from various corners of Eurasia. The overwhelming proportion of the ancestry of any given person in the Indian subcontinent, from Punjab to Tamil Nadu, from the Arabian Sea to the Bay of Bengal, binds together the heritage of three peoples. First, the longstanding residents of South Asia who were descended from the original migrants out of Africa. Second, farmers and pastoralists from the hills of western Iran. And finally, Indo-Aryan peoples who arrived in chariots and drove their cattle before them.

Meenakshi Temple, South India

As noted on the podcast, the slippery and sometimes sloppy usage of labels can mislead as much as illuminate. The term “Indian” can refer to many things, whether it’s a geographic landmass, or, people. More esoteric but still widely used terms such as “Indo-Aryan” are properly linguistic, but they have gained ethnic connotations. A shorthand that communicates, and sometimes, distorts.

In some of the scholarly literature, and on the podcast, you may hear terms such as “Iranian farmer” without context. By this, we do not mean the farmers of modern Iran, but the people nearly 10,000 years ago who lived in what became Iran, and began to herd goats and grow wheat. These people then migrated eastward, eventually to India. Of the great farming cultures of the Middle East that arose with agriculture, these were the easternmost extension.

Obviously, the same caveat applies to the “steppe ancestry”, which is associated with likely Indo-European peoples, from the early Yamnaya to the successor Corded Ware, Andronovo and Sintashta cultures. The fact is that there were different peoples on the steppe before these cultures arose, and there were, and are, people on the steppe after they left the stage of history. But, in the context of Indian history what we mean by “steppe ancestry” are these particular cultures, and the genetic imprint we see on the steppe between the Volga and the Aral Sea, and later among the peoples of India after 2000 BC. The term is not genetic, but specific.

Indra atop his mount, an elephant

The latest genetic work aligns with earlier theories that the Indo-Aryans arrived in India after the decline of the Indus Valley Civilization. All signs point to their connection to peoples on the Eurasian steppe, whose origins are themselves a melange of West Asian, European and Siberian. This has led some commentators to suggest that the Indo-Aryans were “alien invaders.”

In sharp contrast, Indian nationalists have long been keen to point out that the earliest texts written down from the oral epics of the Indian Aryans do not seem to record a memory of a land outside of South Asia. In the Vedas, the oldest of the memories of the Indo-Aryan tribes, the Thunder God Indra sits atop an elephant, an Indian beast if there ever was one.

Though the origin of the Indo-Aryans was likely outside of the continent, it is important to remember that their cultural and historical identity as we understand them today seem to have been forged in the Indian subcontinent. The Vedas themselves bear the imprint of non-Aryans words, indicating that by the time the warlike and pastoralist tribes began to fashion the seminal epics which defined their identity, they had already become of the soil of the subcontinent in a deep sense.

Diversification of the Dravidian languages 4,500 years ago

One of the major dichotomies in the prehistory of South Asia on the edge of the history, from the arrival of Alexander the Great in the north to the Sangam period flourishing in the south, is between Indo-Aryan and Dravidian. Often, the Indo-Aryans are posited to be newcomers, while the Dravidians are aboriginals. But new research in linguistics and archaeology is pointing to the conclusion that Dravidian languages themselves diversified in the period after 2,500 BC. In other words, not very much earlier than when the Indo-Aryans arrived in the subcontinent.,

Though the Dravidian populations of the south often lack the ancestry from the Eurasian steppe, so common among Brahmins, in particular, they invariably show signs of being descended from the ancient Iranian farmers. Like Indo-Aryan speaking peoples, the Dravidians are themselves likely a fusion of newcomers from the north and west, and indigenous hunter-gatherers. The linguistic evidence, along with the start of the South Indian Neolithic in 2,500 BC, indicates that Dravidian-speaking peoples forded the path for the Indo-Aryans that came after them.

What genetics has told us over the past generation is that most of the world’s populations are mixes between very different groups of people. 10,000 years ago no one lived in the world who looked much like modern Indians. Or Northern Europeans. Or, likely Southeast Asians. And so on.

Underneath all the statistics, the new science and old history, the final truth is that in the game of precedence and indigeneity, no one really comes out ahead. It’s been a long and complicated dance between many different peoples, and everyone’s ancestry leads to both outsiders and insiders.

Interested in learning where your ancestors came from? Check out Regional Ancestry by Insitome to discover various regional migration stories and more!


India is eternal but Indians are not was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

The Insight Show Notes — Season 2, Episode 3: ANI, ASI, IVC and The Genetics of India

Filed under: Genetics,History,India,science — Razib Khan @ 3:49 pm
A scene from an ancient Indian epic

This week on The Insight (Apple Podcasts, Stitcher and Google Play) we discussed how the genetics of 25% of the world’s population, the people of South Asia, came to be. It’s a journey of thousands of years.

We cited the preprint, The Genomic Formation of South and Central Asia.

Additionally, we cite a chapter in David Reich’s Who We Are and How We Got Here, where he discusses the genetics of India, and how it’s analogous to Europe.

A cover story from India Today, 4500-year-old DNA from Rakhigarhi reveals evidence that will unsettle Hindutva nationalists, was also referenced. Please read with caution! The research has not been published, and there are likely going to be changes based on new results (actually, probably certainly from what I have heard)….

There was a discussion of some technical, but important, statistical genetic tests to infer admixture. The paper in Genetics, Ancient Admixture in Human History, outlines these methods in detail. The three and four population tests, as well LD decay estimates of admixture time are all discussed in this paper. All are alluded to or discussed in the podcast.

Linguistic families in South Asia

There was extensive discussion of the various language families in India, in particular, Indo-Aryan, Dravidian, and Munda. We discussed the results of a recent, paper A Bayesian phylogenetic study of the Dravidian language family, which indicates a recent expansion of this language family in South Asia. Also, a new preprint on Munda, The genetic legacy of continental scale admixture in Indian Austroasiatic speakers suggests that the Munda emerged around the same time as the Dravidians.

A lot of ethnographic terms were thrown around with deeper exploration. If you want to follow-up, Elamites from ancient Iran, Indo-European Sintashta culture, and the Bactria-Margiana culture of Central Asia.

We talked about ANI and ASI. The 2009 paper, Reconstructing Indian Population History, introduced these terms and constructs. The Kalash and Pulayar people of Pakistan and southern India respectively were mentioned as modern-day exemplars of ANI and ASI.

Distribution of R1a1a

The distribution of R1a1a in India and Eastern Europe was also discussed, and how it is associated with expanding steppes. Also, caste and its antiquity were discussed, in particular, that modern boundaries between groups seem to have emerged around 2,000 years ago, after several thousand years of admixture between disparate Indian groups. The promise of disease gene discovery in South Asia is a preprint that explores the relevance of this endogamy today for health risks.

Linguistic isolates Burusho and Nihali were mentioned. And, the development of the “Yankee” identity, which Razib analogized to Indo-Aryans!

Interested in learning where your ancestors came from? Check out Regional Ancestry by Insitome to discover various regional migration stories and more!


The Insight Show Notes — Season 2, Episode 3: ANI, ASI, IVC and The Genetics of India was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

September 19, 2018

The Insight Show Notes — Season 2, Episode 2: The Greatest Human Journey

Filed under: Genetics,hawaii,Podcast,science — Razib Khan @ 8:10 pm

This week on The Insight (Apple Podcasts, Stitcher and Google Play) we touched upon arguably one of the greatest human journeys of humankind, the expansion of the Polynesians across the Pacific.

Bishop Museum

Spencer discussed his visit to the Bishop Museum in Hawaii.

We discussed broadly the interesting confluence of biology, geology, and history one can see in Hawaii. The book The Monkey’s Voyage: How Improbable Journeys Shaped the History of Life discusses the biogeographic characteristics of many islands, including Hawaii.

We discussed the context of Polynesian languages and culture as part of the broader zone of Austronesian language and culture.

The extent of Austronesian languages

Austronesian societies spread over the last 6,000 years from Taiwan to the far west in Madagascar, and far east in Easter Island. The expansion into Polynesia was prefigured by the expansion of the Lapita culture between 1500 BC and 500 BC.

The Lapita culture is defined by its unique pottery. But curiously the usage of pottery disappeared among the Polynesians, the likely later descendants of the Lapita people. Razib mentioned how there is some evidence that cultural bottlenecks and small populations can result in loss of skills such as pottery.

On the other hand, Spencer pointed out that the Polynesians also did not practice rice agriculture, unlike other Austronesian societies. Instead, they expanded with a cultural toolkit of taro, which likely was adopted from the peoples of Near Oceania, New Guinea, and Melanesia.

Sweet Potato

Additionally, Spencer brought up the fact that the cultivation of sweet potatoes in Polynesia likely indicates contact between Polynesians and the peoples of South America. The genomic evidence that Polynesian sweet potatoes derive from South American ones is conflicted. Spencer mentioned that the word for “sweet potato” in Quechua, the language of highland Peru, is kumar. In Hawaiian, it is ku ala.

We mentioned in passing Thor Heyerdahl’s view that there was a South American migration to Polynesia. But the genetic, cultural, and archaeological evidence does not support this.

The Polynesian mtDNA motif was mentioned. With a high frequency in Polynesia, the mtDNA lineage seems to have spread from the west, in line with the idea of a migration to the east. In contrast, the Polynesian Y chromosomes show a mix of Asian and Melanesian heritage.

Much of the arguments hinge on the argument of whether the expansion of Austronesians into the Pacific was via the “slow boat” or “express train” model. The slow boat model suggests widespread cultural and genetic mixture gradually with the Austronesian expansion through Melanesia. The express train model implies a more rapid migration with far less interaction. Culturally the adoption of taro cultivation aligns with the slow boat thesis. As does the existence of Melanesian Y chromosomes across the range of Polynesians. But the overwhelming Asian nature of Polynesian mtDNA lineages fits the express train model.

One way that scholars have reconciled this is that there was a slow expansion of the Lapita people, but that they only assimilated Papuan and Melanesian men into their matrilineal communities. This broad framework was reinforced with the publication of genetic results from native Hawaiians, which showed a minority ancestry from a Papuan-like population.

But wait, there was a twist! Ancient DNA now shows that the Lapita people had almost no admixture with Melanesian people! Follow-up results from Vanuatu and Tonga confirm that the Lapita people had no admixture from Melanesians. Rather, in Vanuatu 2,500 years ago the Lapita people are replaced by an almost entirely Melanesian population, and the Melanesian ancestry begins to show up in Polynesians after this period. The conclusion then is there were multiple migrations into Polynesia!

Spencer and I concluded that the broad sketch is now established, but a lot of complicated details need to be worked out. Instead of express trains or slow boats, some researchers now wonder if Polynesia was more like a subway network.

Interested in learning where your ancestors came from? Check out Regional Ancestry by Insitome to discover various regional migration stories and more!


The Insight Show Notes — Season 2, Episode 2: The Greatest Human Journey was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

Hawaii: complicated a journey to paradise

Filed under: anthropology,Genetics,hawaii,science — Razib Khan @ 7:11 pm
The extent of Austronesian Diaspora

Ask any American what they think when you say the word “Hawaii,” and certain words will no doubt reoccur from person to person. That’s because certain images, feelings, come to mind. A gentle breeze, beaches, and volcanoes. The 50th state has been the byword for paradise on the mainland. A certain sense of Hawaii is part of American popular culture.

But Hawaii is a real place with real people. It isn’t a dreamland. Rather, it is one of the most isolated large islands in the world. Over 2,500 miles from the nearest continent, there is only a single terrestrial mammal native to the islands: predictably, a bat!

Obviously, the island is crawling with mammals today. Nearly 1,000 years ago voyagers from the lands of the western Pacific landed on the Society Islands, which includes famed Tahiti, and then sailed northward to the Hawaiian archipelago. When the ancient Polynesians settled Hawaii they did not arrive alone. They brought with them pigs, chickens, and dogs. Naturally, rats tagged along as unwanted passengers.

Humans arrived in Hawaii in catamarans

But the settlement of Hawaii by humans was the end of a long journey which began thousands of years earlier in the mists of prehistory. Six thousand years ago a small group of stone-age seafarers, who we call Austronesians, journeyed south from Taiwan and settled the northern Phillippines.

But they did not stop there. Over a period of thousands of years, these ancient mariners spread out over Southeast Asia, sometimes introducing intensive forms of rice agriculture and their distinctive language. But they did not stop there. For whatever reason, these were a people who wondered what was over the horizon, even if it was the deep blue ocean. They moved on west and east. Over 1,000 years ago their descendants reached the western Indian Ocean, mixing with the Bantu farmers of eastern Africa and occupying the island of Madagascar. In the other direction, Austronesians moved into Oceania, abandoning rice and adopting taro from Melanesians. Less than 1,000 years ago the Pacific expansion finally crested, as Polynesians settled in New Zealand, off the coast of Australia, Easter Island, 2,300 miles west of South America. And of course, they ventured north to Hawaii, an isolated ecologically rich and unique jewel in the midst of the Pacific.

In Southeast Asia, the Austronesians merged with native populations of farmers which migrated out of southern China earlier. But as they moved west and east they encountered very different populations, whether it be African farmers and pastoralists, on the one hand, or Melanesians in the case of the ancestors of the Polynesians.

Citation: Kim SK, Gignoux CR, Wall JD, Lum-Jones A, Wang H, Haiman CA, et al. (2012) Population Genetic Structure and Origins of Native Hawaiians in the Multiethnic Cohort Study. PLoS ONE 7(11): e47881

And just as the people of Madagascar, despite speaking a language closest to those spoken in Borneo, have a blended with nearby populations. Polynesians carry signatures of interactions with the peoples of Near Oceania, which includes New Guinea, Australia, and Melanesian islands in the western Pacific, such as the Solomon Islands and New Caledonia.

As genomics began to illuminate all the relationships between human populations, in 2012 a paper was published that surveyed the genomes of many native Hawaiians. The results were clear: the indigenous peoples of Hawaii had a dominant signature of ancestry shared with mainland Asian peoples, but also a minority component that had more affinities with the peoples of Near Oceania.

Lapita culture sites

This result was relevant to what traditionally had been termed the “express train vs. slow boat” models of the settlement of Polynesia. The “express train” hypothesis implies that the Austronesian Lapita culture rapidly pushed out of maritime Southeast Asia, with minimal interaction with local Papuans and other Melanesians. In contrast, the “slow boat” model meant that the expanding proto-Polynesians mixed with Papuans and Melanesians as they spread eastward more gradually, creating a fused culture which pushed onward into the far Pacific.

The results above, along with maternal and Y chromosomal lineages seem to support the “slow boat” model. Not only are all Polynesians, including Hawaiians, descended from Southeast Asian farmers, but their ancestors also include the people who first pushed to the edge of the Pacific. These were the ancestors of Oceanians who settled New Guinea, Near Oceania, and Australia more 40,000 years ago with the first “Out of Africa” migration.

Citation: Skoglund, P., Posth, C., Sirak, K., Spriggs, M., Valentin, F., Bedford, S., … & Fu, Q. (2016). Genomic insights into the peopling of the Southwest Pacific. Nature, 538(7626), 510.

So case closed? Not exactly. Science and history are often more complex than our elegant human imaginings. Over the past few years, the field of ancient DNA has come upon the scene to disturb hypotheses and provoke the development of new ones. Now researchers can see snapshots of the past with much crisper detail than would have been the case in the past.

Two papers have helped reshape our understanding of the peopling of Polynesia. First, a 2016 paper showed that samples of ancient Lapita people don’t show any admixture from Melanesians. This is in accordance with the “express train” model, which the genetic heritage of modern Polynesians presumably refuted!

An immediate solution to this conundrum is that the old models were too simple. That there wasn’t just a simple migration outward, but rather several, and that Melanesian ancestry arrived later. Within the last 2,000 years.

A paper published in 2018 added more nuance and clarity to what may have been going on. Today the island of Vanuatu is considered to be Melanesian and is settled by people of predominant Oceanian heritage. But ancient DNA from 3,000 years ago yielded individuals of nearly total Asian heritage. But by about 2,000 years ago these people were replaced, by the ancestors of modern Melanesians, as later samples show overwhelming Oceanian heritage.

Poke is a melange of flavors and ingredients from the four corners of the world

Where does this leave us? Appropriately, a paper appeared with the title “Human Genetics: Busy Subway Networks in Remote Oceania?” was penned as a response to all this uncertainty and confusion. The title says it all, doesn’t it?

These findings may actually be consonant with recent archaeological results that eastern Polynesia and New Zealand were subject to a massive demographic expansion and radiation beginning around ~1,000 years ago.

Today modern Hawaii is a melange of peoples, reflected in its cuisines, such as Poke, which has been inflected and modified by new ingredients brought by immigrants from the mainland and Asia. And yet perhaps this was always so, as paradise was never as serene and eternal as we may dream in our imaginings. Rather, Hawaii and the Hawaiians were products of daring voyages generation after generation, and the waxing and waning of peoples and cultures, bringing together diverse and disparate threads of the human expansion out of Africa.

Interested in learning where your ancestors came from? Check out Regional Ancestry by Insitome to discover various regional migration stories and more!


Hawaii: complicated a journey to paradise was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

August 28, 2018

The dual engines of modern science

Filed under: science — Razib Khan @ 9:38 am

A few years ago Armand Leroi wrote The Lagoon: How Aristotle Invented Science. Some people immediately made a critique that actually, science, as we understand it, is really the creation of early modern Europe. That Aristotle and his fellow Ancients, or physicians and astronomers of early medieval Islam, or the scholastics of the high Middle Ages, didn’t “really” do “science.”

I think most of us understand where this critique is coming from. But, even if you grant the objection if Aristotle was alive today, would he be a scientist? Of course, he would go into science! And, he would probably a good one. Perhaps a great one. Why? Because he had the curiosity, cognitive skills, and, there is a culture that would allow him to flourish. To me, the biggest difference between early modern Western science, as it emerged in the 17th and 18th centuries, and what came before, is that it was a cultural concert of thinkers, a vast constellation of minds and minions.

In contrast, much of ancient science was driven by singular geniuses.

This brings me to the massive replication effort that just got published in the journal Science:

There are lots of angles to this story. Mostly good. But Jonathan Haidt pointed out how important this makes collaboration and a culture of truth-seeking within the enterprise. Alexandra Elbakyan has stated that her scientific activism is driven by “communist ideals.” And though I dislike Communism, I do think there is something fundamentally communistic about science. In Uncontrolled Jim Manzi points out that within the world of science there are very strong norms about honesty. A major issue with scientific fraud is scientists are trusting.

But then there is the von Neumann factor: geniuses can accelerate and open up whole landscapes of research. They do a “different kind of science.” It’s less culturally embedded, and less social and incremental. They are the sparks which fly in the darkness.

The moral of the story, if there’s any, is that modern science is a synthesis of these two aspects. There is the “industrial” aspect of scale, efficiency, and incrementalism. One step at a time into the darkness, cautious and continuous.

And then there are the startling breakthroughs. Sometimes those breakthroughs are genius and insight. Consider the story of the emergence of String Theory outlined in Lee Smolin’s The Trouble with Physics. Smolin is a skeptic of String Theory, but in the book, he describes how rapidly it took the scientific world by storm, just by force of its insight and elegance.

Then there are cases such as CRISPR, where several different groups seem to have “stumbled” onto it. The genius here is less in the humans than in what nature had invented. Nevertheless, in a few years, CRISPR radically transformed the possibilities in “genetic engineering.”

Going forward, big collaborative science will keep lumbering on. It will play the role that it has played for decades, driving translation, laying the seedbed for innovation. Normal science. But every now and then a spark will fly, and a new flame will explode. Genius still has a role to play.

August 15, 2018

The Insight Show Notes: Episode 32, So you want to be a geneticist…

Filed under: anthropology,Archaeology,Genetics,science — Razib Khan @ 5:45 pm
Drosophila

This week on The Insight (Apple Podcasts, Stitcher and Google Play) we talk to an “early career” geneticist, Austin Reynolds. A graduate of Indian University and University of Texas-Austin, he is currently a post-doctoral fellow at University of California-Davis.

Alfred H. Sturtevant in his own “fly lab”

As a field, genetics is officially a bit over a century old. Though Gregor Mendel made his key discoveries fifty years before. Since the year 2000 genetics has undergone a revolution driven by sequencing technology and more powerful computing. Around 2010, a different revolution began, which Austin has been a part of, involving the synthesis of archaeology and genetics with the field of ancient DNA.

The first ancient whole-genome analysis, Ancient human genome sequence of an extinct Palaeo-Eskimo. Also, the Neanderthal paper which revolutionized our understanding of our relation to this lineage.

An excellent review of the state of the current research, Ancient Human Genomics: The First Decade. And a preview of the future, Tales of Human Migration, Admixture, and Selection in Africa.

David Reich’s book Who We Are and How We Got Here is a good primer on ancient DNA and population genetics. Highly accessible to the lay audience without sacrificing any of the scientific content.

Loci associated with skin pigmentation identified in African populations.

Nuclear DNA sequences from the Middle Pleistocene Sima de los Huesos hominins.

On career issues, Track the fate of postdocs to help the next generation of scientists.

Interested in learning where your ancestors came from? Check out Regional Ancestry by Insitome to discover various regional migration stories and more!


The Insight Show Notes: Episode 32, So you want to be a geneticist… was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

July 18, 2018

The Insight show notes: Episode 29, The Genetics of China, Han & Beyond

Filed under: China,Genetics,History,science — Razib Khan @ 3:39 pm

This week Razib and Spencer discussed the genetics and history of China on The Insight (iTunes, Stitcher and Google Play).

Chinese history looms large in the podcast, and there are many books one can read on the topic. In particular, John King Fairbank’s China: A New History is one of the rest comprehensive treatments. To understand what’s going on in China today it’s probably good to have at least one survey book or course of its past under your belt!

For the purposes of this episode though, you can just check out a list of Chinese dynasties, if you just want a visual outline of the timeframe and period which Razib and Spencer covered in the podcast.

In relation to the genetics alluded, for genome-wide patterns of relatedness across Chinese regions: Genetic Structure of the Han Chinese Population Revealed by Genome-wide SNP Variation. This 2009 paper uses 350,000 markers from 10 provinces to perform exploratory analysis of genetic structure within China.

More recently, A comprehensive map of genetic variation in the world’s largest ethnic group — Han Chinese, is a preprint that utilizes whole-genome sequencing to assemble an even larger dataset.

For maternal mtDNA, Large-Scale mtDNA Screening Reveals a Surprising Matrilineal Complexity in East Asia and Its Implications to the Peopling of the Region. For Y chromosomes on the paternal side, Y Chromosomes of 40% Chinese Descend from Three Neolithic Super-Grandfathers.

To get a sense of how China’s population has grown genetically, see Robust and scalable inference of population history from hundreds of unphased whole-genomes. The figure to the left shows the “Out of Africa” bottleneck, and then demographic expansion in the last 50,000 years. “CHB” represents Chinese sampled in Beijing. Along with “GIH”, who are Gujuratis, and “CEU”, a Northern European American cohort from Utah, the Chinese exhibit explosive growth in the last 10,000 years.

There is extensive discussion of the environment and geography of China, and how it related to agricultural expansion and migration southward. The Retreat of the Elephants by Mark Elvin chronicles this process of the expansion of rice farming into the jungles of southern China through natural history and human geography.

Though most people are aware of the Mongols, fewer are cognizant of the interregnum between the Han and Sui-Tang, when many steppe nomads settled in China, Buddhism took root, and many elite Han lineages migrated from the north to the south. For those curious about this period, China Between Empires: The History of the Northern and Southern Dynasties is an excellent introduction accessible to all.

Finally, there was extensive discussion about the future of Chinese science. For a deeper exploration of that that, see A Chinese Province Is Sequencing One Million of Its Residents’ Genomes and China Has Already Gene-Edited 86 People With CRISPR.

Interested in learning where your ancestors came from? Check out Regional Ancestry by Insitome to discover various regional migration stories and more!


The Insight show notes: Episode 29, The Genetics of China, Han & Beyond was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

June 28, 2018

Have your exome sequenced for $29.99

Filed under: DNA,Genetics,sales,science — Razib Khan @ 9:11 pm

Just a reminder that for the rest June Helix DNA kits with the cost of an Insitome app. Buy Regional Ancestry, Metabolism, or Neanderthal, and start your lifelong DNA journey with Helix for just $29.99! A great gift idea.

That means for the cost of an app Helix will sequence more 30 million markers in your genome. In contrast, rival genotyping companies only look at 500,000 to 1,000,000 markers.

Cost of use: FREE

The 30 million markers Helix sequences include your whole exome. The part of your genome which is involved in coding for proteins, and so impact your appearance and function. The Helix system also includes markers outside of the exome to further map your genome more effectively.

Insitome’s apps, whether it be Regional Ancestry, Metabolism, or Neanderthal are windows into the whole landscape of modern day personal genomics. Once Helix sequences you the data is banked for later use.

When new apps are developed on the Helix platform, your future purchases will only include the cost of the app! Entering the ecosystem now means that you will never have to pay the initial cost of the sequencing kit.

What are you waiting for? Get the Helix DNA kit and jump into the ecosystem now!


Have your exome sequenced for $29.99 was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

June 27, 2018

Genetics of uniqueness

Filed under: Genetics,indigenous-people,science — Razib Khan @ 1:54 pm
Ati woman from the Philippines
Hui Chinese Muslim man

True genetic isolation is hard to pull off. Human populations tend to mix when they are in close proximity.

Consider the Hui people. These are Muslims who live across China and speak the local Chinese dialect of their locale. The Hui claim descent from Central Asians and Persians who arrived in China around 1,000 years ago. But the vast majority of their genomes are no different from the Han Chinese. Physically they are impossible to distinguish from Han Chinese unless you take note of their attire.

How can that be when they are so culturally different? For example, as Muslims the Hui do not eat pork and consider it unclean. In contrast, for the majority Han pork is dietary staple.

Imagine that the Central Asian ancestors of the Hui arrive 1,000 years ago to China. The historical record suggests that is roughly correct. Each generation is 25 years long, so that’s 40 generations. Since the population of Muslims is small in comparison to the native Chinese, we can ignore the latter, while focusing on the former. If on average 1 out of 20 marriages was between a Han Chinese and a Muslim within the Hui community per generation, after 1,000 years 88% of the ancestry within the Muslim community would be traceable to Han Chinese ancestors. Even though in each generation the overwhelming majority of marriages were within the Muslim community, over time the genetic distinctiveness of the Muslims would diminish.

The lesson is that even a small degree of intermarriage can even out the differences between groups. Similarly, in population genetics one individual moving between two groups per generation is enough to prevent them from becoming distinct. In small populations, which diverge fast, one individual is a substantial proportion of a population. In large populations the divergence is going to be much slower, so even one individual is enough.

An Andaman Islander

So how do populations remain genetically distinct if mixing and homogenization is so easy? The simplest way is simply geography. Consider the Andamanese. These slim and dark-skinned people are the natives of the Andaman Islands, in the middle of the Bay of Bengal. To the knowledge of archaeologists and historians these people have been hunter-gatherers since time immemorial. The only verified continuous such tradition in all of Asia.

The Andamanese likely arrived in the islands during the Pleistocene, when sea levels were lower, and the Andaman Islands were much more accessible from the Southeast Asian mainland. But over the past 10,000 years, as much of the world adopted agriculture, and population turnover occurred in South Asia and Southeast Asia, the Andaman Islands remained relatively untouched due to their isolation.

But it wasn’t just geography. Over the past 2,000 years the Indian ocean has become a major thoroughfare of trade and travel. The Andaman Islands were on a route between India and Southeast Asia. Because of this fact they were often a convenient stopping point to refresh water supplies. But these traders never settled the islands. The local people had a habit of attacking any vessel which tarried too long in their waters.

Pygmies from Central Africa

Unlike many animals humans have complex and evolving cultural practices. The Andaman Islanders discouraged contact with outsiders by maintaining a savage and hostile reputation.

But other groups have remained genetically distinct through symbiosis rather than separation.

The Pygmy peoples of Central Africa are distinguished from their neighbors by their small stature, and hunter-gatherer lifestyle. But they invariably speak the languages of their neighbors. Anthropologists have observed that Pygmies and the farmers who they live nearest to seem to exist in some form of interdependence. Hunter-gatherers can obtain resources from the deep rainforest inaccessible to famers, while the farmers offer the Pygmy people goods which they themselves could not produce.

African farmers and hunter-gatherers have lived in close proximity for over 2,000 years, and yet the Pygmies remain different physically and genetically from their neighbors. Some mixing has occurred, but the Pygmies are as much a separate caste as a different people. Their lifestyle is so different that farmers and Pygmies view each other as profoundly alien and peculiar, despite speaking the same language and occupying nearby geographical space.

Roma in Romania

Isolation then can be both a physical and psychological phenomenon. Some groups, such as the Andamanese, are physically separated from other humans. They add cultural adaptations which reinforce this separation. Others, such as the Pygmies, or the Roma of Europe, are culturally very distinct, and occupy a specific role in the social ecology of their region. In both cases the isolation is strong enough to result in genetic differences between populations of the majority and the isolate.

In many cases these populations are not so isolated in the modern age. In the Andaman Islands most of the tribes now interact with settlers from the Indian mainland. Only the people of North Sentinel island remained truly isolated and cut off from the rest of the world. Meanwhile, the Pygmy people of Central Africa have been caught up in the massive civil wars that have wracked that region of the world since the 1990s. In other cases, as with the indigenous Negrito people of the Philippines, their biological and cultural assimilation into the dominant Austronesian mainstream is proceeding to such an extent that they may no longer being a distinctive people by the end of the 21st century.

For many peoples the 21st century will be the twilight of their solitude, as they merge into the world.

Interested in learning where your ancestors came from? Check out Regional Ancestry by Insitome to discover various regional migration stories and more!


Genetics of uniqueness was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

June 20, 2018

Three drinks for the ages

Filed under: Alcohol,Coffee,Genetics,milk,science — Razib Khan @ 9:33 pm
Irish Coffee

The “Irish coffee” is a a delicious concoction. Coffee, alcohol, and dairy. What more can you ask for? Man does not live on bread and water alone. Cafes and bars are thick on the ground in large cities, but also grace country roads. Coffee and alcohol are congenial to conviviality among settled peoples, while milk is the staff of life for many pastoralists, consumed raw or turned into cheese.

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Of the three, coffee is a new on the scene, discovered within the past 1,000 years. The consumption of milk, whether raw or as cheese, goes back to prehistory. But on the geological scale it a recent cultural development. In contrast, the imbibing of alcohol in some form is probably as old as humanity itself, albeit not as a pint in the pub.

Alcohol is produced naturally by the fermentation process, a metabolic pathway which is far more ancient than the oxygen metabolism that has been dominant for the past few billion years. Humans are omnivores, and our ancestors consumed overripe fruit which had fermented to the point of producing alcohol byproduct. Meanwhile, “good bacteria” in our guts also produced alcohol.

This is not a bad thing. Alcohol is nutritious in that it provides calories.

Though in modern societies we “count our calories”, and the richness of a deep and dark beer is not always a selling point, for the vast majority of our species’ history those calories were a feature, not a bug.

Early civilization ran on beer. The Sumerians even had a goddess of beer, Ninkasi. The workers who built the pyramids of Old Kingdom Egypt were given rations of beer. In other words, the wonders of the ancient world were fueled by alcohol!

And this is not just forgotten history. Until very recently much of the world was awash in alcohol, whether it be beer, wine, or various distilled spirits. Public and private drunkenness were one of the major reasons behind the emergence of the American “temperance” movement. Though Prohibition was deemed a failure, American alcohol consumption has never recovered to its earlier highs.

One of the reasons that Americans, and many other peoples, drank so much is that alcoholic beverages is that not only did they provide calories, but they were often more potable than conventional water. Ancient humans in hunter-gatherer bands did not have to contend to cholera, but the first village societies, and those who lived in early modern cities, lacked modern sanitation. Safe drinking water was one of the major achievements of 20th century engineering, and obviated the role that alcohol had traditionally played in quenching the thirst of the common man.

But alcohol is not a matter just of history, biochemistry and engineering. Humans differ in their ability and capacity to metabolize alcohol due to variation on their genes. In particular, ADH and ALDH2. The ADH genes produce enzymes which breakdown alcohol for processing by later biochemical steps, one of which is catalyzed by the product of the ALDH2 gene.

If you’ve ever seen someone with the flushed face characteristic of having had too much to drink, they may have a mutation on ALDH2 which means that they don’t process acetaldehyde very well. As the cells build up acetaldehyde, a host of physiological reactions kick in. Research has shown that those who exhibit these reactions are much less likely to be alcoholic.

In contrast, those with mutations on ADH tend to process alcohol very well indeed. But in the process they produce more acetaldehyde than the body can handle, resulting in physical discomfort. And similarly to the ALDH2 mutation these individuals are less likely to become alcoholic.

Genetic variation in the ability to process alcohol is a consequence of the long history of human omnivory. In contrast, the evolutionary history around our consumption of milk is much more straightforward and strange. For the vast majority of our species’ existence adults have not had the ability to digest milk sugar, lactose. This is a characteristic we share with all other mammals. The adaptive reason for this is likely that it encourages and forces weaning, so that mothers can bear other offspring.

And yet a minority of modern human adults today can digest milk. How? Why? The LCT gene produces an enzyme lactase, and mutations in this gene allow humans in Europe, parts of Southern Asia, East Africa and the Near East to continue to drink milk into adulthood. Over the past 5,000 years unique mutations in Europe and South Asia, in Arabia, and in Africa, have all been strongly selected.

In Denmark the mutant allele is now at frequencies as high as 90%.

Ancient DNA tells us that the ability to digest milk sugar into adulthood did not arise with agriculture and sedentary lifestyles. It is not implausible that Neolithic people who domesticated goats and sheep fermented milk to produce cheeses, where the sugar was broken down to make it more palatable. But the adaptation to a predominantly dairy dependent lifestyle only emerged with full-blown pastoralism, over the past 4,000 years. The earliest pastoralists on the Bronze Age Eurasian steppe carried the lactase persistent genetic variant, but only at low frequencies.

Dairy is an essential part of the modern food pyramid, at least for the USDA. But perhaps it tells us more about our evolutionary present than the evolutionary past. So often we talk about evolution as a dynamic of the deep past. But with lactose tolerance we see evolution as a process which is just initiating.

Finally, there is coffee. Though variation on the CYP1A2, Cytochrome P450, effects how fast caffeine is metabolized, coffee is such a recent cultural invention that it is unlikely that there are any adaptive dynamics related to it on a genetic level. Rather, CYP1A2 is locus which controls processes designed to cope with toxic chemicals by breaking them down. Caffeine in some ways is such a chemical, and those who metabolize it fast need to drink more coffee to feel its effects than those who have more efficient metabolization.

The effect of caffeine on humans is literally inefficiencies of bodily detoxification.

Milk nourishes. Alcohol both nourishes and alters the mental state of those who imbibe it. In contrast, caffeine does not nourish, but stimulates. For the past few million years our species likely never interacted with caffeine, but we were pre-adapted because of our consumption of a wide range of plants which manufacture chemical defenses.

The legend of coffee dates back 1,000 years, when an Ethiopian goatherd saw one of his animals behave strangely after eating a coffee plant. Within the next five hundred years coffee beans were cultivated across the hillocks of the lands around the Red Sea, from Ethiopia to Yemen, and became part and parcel of Islamic culture. To this day the coffeehouse is a major social and cultural nexus in the Middle East, though colonialism has taken it far afield, from Java to Colombia.

By the Renaissance coffee had reached Europe, and the proliferation of coffeehouses, and their stimulative effects, may have triggered the early modern Enlightenment intellectual revolution. While alcohol softens and dims the outlines of world around you, coffee is a stimulant which sharpens our perceptions and accelerates our cognitive pace.

Coffee, alcohol, and milk, are such central aspects modern culture that it is hard to imagine our existence without them. Though there is genetic variation in how we can process them, their relevance to our lives transcends biology, and extends to economics, history, anthropology, and in the case of wine, religion. Though they may not be the ambrosia of the gods, modern civilization arguably stands on the shoulders of these beverages.

Wondering if you are lactose tolerant based on your genetics? Check out Metabolism by Insitome.


Three drinks for the ages was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

May 25, 2018

Arise the coalescent!

Filed under: Biology,Evolution,Genetics,science — Razib Khan @ 12:14 pm
Citation: Modeling Human Population Separation History Using Physically Phased Genomes

Evolution is sometimes difficult to comprehend in terms of how it plays out in your mind’s eye. This is different from believing that evolution occurred. Evolutionary ideas were in the air when Charles Darwin and Alfred Russell Wallace both developed a theory of morphological change and speciation driven by adaptation in the middle of the 19th century. Their genius was introducing natural selection as the motive force underlying the change. But both of these thinkers lacked a true mechanism of heredity, so the formal extension of the field was hobbled.

With the emergence of genetics in the years after 1900, evolutionary science developed into a new and powerful form, what we now call the “Neo-Darwinian Synthesis.” This project combined the descriptive richness of natural history, the explanatory power of classical conceptual Darwinism, and the formal precision of population genetics.

The Neo-Darwinian Synthesis rests to a great extent on population genetic models. The most elementary of those models is that of the Hardy-Weinberg Equilibrium (HWE) — a large random mating population not subject to selection or drift. Deviations from the conditions of these models allow us understand the processes that are occurring in specific populations.

In the lab, researchers use matings between organisms such as Drosophila that deviate from the assumptions underneath the models, and see what the outcomes are. Scientists mate together flies with similar or dissimilar traits, violating random mating. They select individuals based on their characteristics, or collapse reproductive pedigrees down to a family lineage to explore inbreeding, introducing selection and random genetic drift.

But laboratory research can be both time intensive and tedious. With the rise of powerful computing tools in the last half of the 20th century scientists realized that they could simulate outcomes of their models. Just like in an experiment, researchers could change the conditions, the parameters, and see the results to the final outcome!

State of the art simulator, 1985

In the beginning, the power of simulations and computing seemed almost magical to researchers. No more time intensive sampling in the field, or expensive construction of laboratory facilities.

But over time, they began to realize that simulations also have their limitations. Computer memory and disk space costs money too, and scientists quickly found that the law of scarcity was not abolished. They couldn’t explore infinite possibilities because infinite took forever, even in a computer.

Imagine that you start with a few hundred individuals and simulate them randomly “mating.” You stipulate that their population grows 2% every generation. After a 100 generations, your population size is 10 times larger. The possible number of “mates” in your program is now 10 times greater, and there are so many more possible interactions. Anyone who has tried to work with large files knows that computing resources are finite, and simulations running forward in time run into the limits of that finitude soon enough.

But what if you moved back in time? Imagine you began with 10,000 individuals, and traced the ancestors of these 10,000 back across the generations. Genealogies can be complicated. But consider a single gene copy in your body, and compare it to another copy in another person. At some point in the distant past, the two copies share a common ancestor — they coalesce.

The coalescent sounds science fictional, but really it’s just a way to work backward from the genetic data you have now, to the past. You can create a tree of relationships back into the distant past, reversing direction with a genetic time machine. And the beauty of the coalescent from the perspective of 2018 is that computationally it is much more feasible to work back in time. With each step, you have fewer and fewer branches in the genealogy to model — back to a single common ancestor.

Instead of being overwhelmed by computational tasks, the coalescent converges upon the elegant simplicity of the last common ancestor, bring together late 20th century mathematics, 21st century computing, and the original conceptual insight of Darwin and Wallace of common descent.

Explore your Regional Ancestry story today.


Arise the coalescent! was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

May 16, 2018

The tribe more diverse than all of Asia!

Filed under: Africa,Genetics,science — Razib Khan @ 1:17 pm
Bushman

In 2010, a paper, which sequenced the whole genome of Bishop Desmond Tutu, revealed that the San Bushmen of South Africa show more genetic difference between two men from different tribes than the differences between a European and an East Asian. In other words, two San Bushmen men from different populations within South Africa are more genetically distinct than a Chinese person is from a British person.

A follow-up paper from 2014 revealed that over the course of human history, the San Bushmen in fact had the “largest population” of any modern group. This seems surprising and ridiculous. There are over 1 billion Han Chinese, and only 100,000 San Bushmen.

Citation: Khoisan hunter-gatherers have been the largest population throughout most of modern-human demographic history

How can this be?

The first thing to keep in mind is that we’re talking about genetic diversity. When you look at the genome of a San Bushmen individual, it’s a lot more genetically diverse than that of a Han Chinese individual. A typical San Bushmen has more than 4 million genetic variants (SNPs), while a typical Chinese has only over 3 million genetic variants. This difference reflects population history.

One of the major keys to solving this mystery is to remember that the “Out of Africa” migration imposed a bottleneck on all non-African populations. That means that 50 to 100 thousand years ago, a small group of humans were the ancestors of all groups outside of Africa. All non-African populations exist in the shadow of this bottleneck, from the over 1 billion Han Chinese to a few hundred tribesman in the Amazon.

In contrast, the ancestors of Africans did not experience such a bottleneck.

The number of genetic variants that Africans carry did not decrease due to an “Out of Africa” bottleneck, and of all the people of Africa, the San Bushmen seem to have occupied a wide zone of southern Africa in their current state from an immemorial time. This stability has left an imprint on their genome, which is more genetically diverse than any other human group.

If you could use a time machine to count the number of people in the groups of humans which gave rise to the San Bushmen, they would always be larger than the small migration “Out of Africa.” This is why a tribe of San Bushmen have more genetic diversity than billions of Asians!

Interested in learning where your ancestors came from? Check out Regional Ancestry by Insitome to discover various regional migration stories and more!


The tribe more diverse than all of Asia! was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

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