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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

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.

August 6, 2018

Genetics is not about “dunking” on Hindu nationalists

Filed under: Aryans,Genetics — Razib Khan @ 2:17 pm

I need to weigh in real quick about something I’ve been noticing: geneticists don’t do genetics because they are excited about debunking views promoted by some Hindu nationalists and other Indians of a variety of political stripes. In fact, most non-Indian scientists (as in people who don’t live in India) are not totally savvy to the political and social context in South Asia, and so are not aware of how their results may be taken.

Unlike some scientists, I tend to take a dim view of those who assert we need to be careful about how results are going to be interpreted. Science is science. Interpretation is society. Therefore, I don’t particularly care if someone’s cherished views are refuted.

That being said, I have seen on Twitter and elsewhere exultation by anti-Hindu nationalists about new genetic findings, where individuals are wrong in many details of the implications. In the general broad sketch, they understand some implications, but they clearly haven’t paid attention to the science closely, nor do they comprehend it.

There are many examples of confusions and misimpressions. Here is one: the idea that “Vedic civilization” is exogenous to South Asia. I think we need to be very careful about this because I think one can make the case (and this is my position) that by the time most of the archaic mythos of the Indian Aryans crystallized these people were already highly Indianized. To put the political implications on the table, they were much more assimilated in their elite culture than the Muslim rulers of India or the British ever were (and let’s be honest, these are the comparisons people care about).

Rough back-of-the-envelope calculations on my part suggest that ~15% of the total ancestry of all South Asians is steppe derived. That is, about 50% ANI, which is 30% steppe (70% Indus Periphery). Is this a lot? Or not a lot?

Interpretations differ.

August 3, 2018

Why I don’t accept the para-Munda hypothesis

Filed under: Genetics — Razib Khan @ 10:50 pm

There has been a discussion of Michael Witzel’s ideas in the comments below. Long familiar with his thesis that a Munda-like language was dominant in the northern Indus valley and in the Gangetic plain, I have also been long skeptical of it.

The reason for me is simple: I have leaned to the position that Munda are intrusive from Southeast Asia. Over the past 10 years my confidence in this proposition as grown. Let’s review

1) They speak an Austro-Asiatic language. Most Austro-Asiatic languages are in Southeast Asia and seem to have spread from the north to the south

2) The Munda have genetic signatures on the Y chromosome and some of their traits which are distinctive to East Asians and totally unrelated to any other South Asians. These genetic signatures are not found in South Asia outside of the Munda areas, and northeast India (i.e., they are not present in the Indus or Gangetic plains).

3) The most common Y chromosome of the Munda seems to be from Southeast Asia. That is, Southeast Asian lineages are basal and more diverse than the ones in India.

4) Genetic data from ancient DNA indicate that Austro-Asiatic people did not arrive in northern Vietnam until 4,000 years ago. To me this, this implies they arrived in India well after 4,000 years ago.

5) We now suspect that Indo-Aryans arrived well after 4,000 years ago to the Indus valley. The Munda and Indo-Aryans could not have met in that region 3,500 years ago in any reasonable scenario.

Let’s assume that Witzel and others are correct that the early Indo-Aryans and the languages/toponyms of the Gangetic plains do not show Dravidian influence. How could that be? It could be that in the northern Indus valley a non-Dravidian language was dominant. Consider Burusho, a linguistic isolate. Mesopotamia was long divided between a Semitic north and a Sumerian south.

Second, the genetic data seem to suggest that some Indo-Aryan groups have more AASI and more steppe than groups to their west. North Indian Brahmins vs. Sindhis are an example. To me, this is indicative of the possibility that the Indo-Aryans pushed past areas where Dravidian languages were dominant, and only AASI hunter-gatherers were flourishing. The lack of a Dravidian substrate is because the AASI groups the Indo-Aryans encountered were not Dravidian speakers.


August 2, 2018

Rakhigarhi sneak-peaks

Filed under: Genetics — Razib Khan @ 11:30 pm

Over at my other weblog, noting that the Indian press is finally starting to simply report the substantive contents of the Rakhigarhi results. As we all know the media can distort and misrepresent, so we need to be cautious and wait on the final paper, mostly because with that the authors can speak freely and without intermediation. But, I have heard through the grapevine the general results, and the results are exactly what Outlook India is currently reporting.

The Rakhigarhi samples themselves aren’t that interesting to me. But, Niraj Rai seems to be pushing the admixture event with IndoA-Aryans after 1500 BC. This could be a misquote, or, it could be that the researchers from various groups now have enough data to fine-tune their parameters so as to narrow down various admixture timing events.

Ancient pigmentation pathways and modern genomics

Filed under: Forensics,Genetics,skin — Razib Khan @ 1:02 am
Piebald horses emerge out of common pigmentation pathways found in humans

Unlike most mammals humans are highly dependent on our sense of sight. This is due to the diurnal nature of many primates. Our ancestors foraged for bright fruit, and so we developed stereoscopic color vision. But eventually the human lineage left the forests of our ancestors, and ventured out to the savanna. We turned our eyes to other uses than detecting fruit, from hunting, to developing a keen eye for art.

Humans are pre-adapted toward color vision

It is not surprising then that humans have had a fixation on the color of our skin and the pelage of our domesticates. Skin is our largest organ, and our complexion is one of the best indicators of ill health.

Additionally, humans have utilized the skin as a canvas upon which to apply tattoos and other coloration so as to indicate group membership. And, as humans from very different geographic regions began to meet each other, any differences in pallor were salient indicators of difference and distinction. Whole people were defined by their color!

In the ancient Near East the Egyptians termed themselves red, while their neighbors to the south were black, and West Asians from the Levant were yellow. Greeks and Arabs distinguished between the ruddy peoples of the north, and the black and brown peoples to the south, with their own ethnicity often defined as being at some sort of equipoise.

Nubians were depicted accurately by the ancient Egyptians

And yet for such an important trait, the genetic elucidation of skin color, and pigmentation more generally, has evaded us until very recently. To be fair, the genetic elucidation of most traits in humans evaded us until the last decade or so, because we did not have genomic tools to explore the whole range of possible genetic sites.

In 2003 the evolutionary biologist Armand Leroi wrote in the afterword of his book Mutants that it was surprising that geneticists were still unclear about what underlay normal variation on the trait of human skin color. This passage was written at an opportune moment. In 2006 a review paper was published, A golden age of pigmentation genetics, which reflected the fact that much had changed since Leroi had written that passage just three years before.

Through analysis of British mixed-race pedigrees geneticists in the 1950s concluded that skin color was controlled by many genes, but that much of the variation was localized to only a few loci. That is, variation on a few genes had a large impact. This means that genomic methods pioneered in the 2000s were well placed to discover the genetic basis of the variation of the trait. If the impact of the mutation was large, then you didn’t need a large sample size to detect it.

75% of the variation in eye color in Europeans is due to one gene

And so they have. Today researchers now know that about half the variation in skin color across populations is due to variation on about ten or so genes. The other half is mostly distributed across the genome. Additionally, they know that the gene that is correlated with blue eye color also effects skin color. Similarly, the gene that causes much of the blondness in Northern Europe is also correlated with skin color. The pigmentation characteristics are usually correlated together. Skin, hair and eyes are all often controlled by the same set of genes.

Though East Asians and Europeans achieve light skin through different mutations, it is also the case that those mutations are found on an overlapping set of genes. Pigmentation pathways are highly conserved in human populations. The wheel is always reinvented in the same way. In fact, the same genes show up over and over across vertebrates.The genetic mutation that results in blonde hair causes the piebald pelage in horses. The mutations associated with red hair in humans are found in the gene that is important in mouse coat color. The gene responsible for much of the difference in pigmentation between Europeans and Africans also has a lightening effect in zebrafish.

There is a great to be done to understanding the genetic basis of many diseases and complex behavioral traits. But with pigmentation genomics has yielded incredible results, producing forensic applications with utility in a wide range of contexts. This is because tens of thousands of years have produced humans who come in all colors, but through simple fine-tuning of the pigmentation pathways which vertebrates had utilized for hundreds of millions of years.

Skin color is a complex topic with numerous historical and anthropological layers. But when it comes to genetics it’s actually surprisingly simple.

You can see your skin, but are you curious about what your genes say about your pigment? Check out Neanderthal by Insitome to learn more!

Ancient pigmentation pathways and modern genomics was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

July 25, 2018

The Insight show notes: episode 30, Genetics and educational attainment

Filed under: Education,Genetics,Psychology — Razib Khan @ 3:47 pm

This week Razib and Spencer discussed the relationship between educational attainment and genetics on The Insight (Apple Podcasts, Stitcher and Google Play) with James Lee, lead author of Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals (published in Nature Genetics).

Here are some more resources: FAQs about “Gene discovery and polygenic prediction from a 1.1-million-person GWAS of educational attainment”. The Atlantic and The New York Times also covered the paper. An op-ed in The New York Times, Why Progressives Should Embrace the Genetics of Education.

The three laws of behavior genetics and the fourth law of behavior genetics are both mentioned. The study was a meta-analysis of genome-wide associations (GWAS), and may have been the largest GWAS published to date.

Much of the discussion centered around intelligence. The podcast with Stuart Ritchie was cited as a useful primer (remember to subscribe with Apple Podcasts, Stitcher and Google Play). You might want to check out Ritchie’s book, Intelligence.

Population stratification was mentioned. Martin et al., and two preprints, Berg et al. and and Sohail et al., tackle this issue in relation to disease and height, and how it confounds our understanding. Lee discussed LD score regression as a way to account for stratification in this particular analysis..

There was extensive discussion of the concept of heritability, where genetics explains variation in a trait.

The Social Science Genetic Association Consortium (SSGAC) and its research projects were referenced extensively.

Each allele seems to effect ~1 week of education. The authors returned more than 1,000 statistically significant markers.

Spencer brought up the “omnigenetic” model. This comes from Boyle et al., An Expanded View of Complex Traits: From Polygenic to Omnigenic.

James mentioned some of Camille Benbow’s work, in particular Life Paths and Accomplishments of Mathematically Precocious Males and Females Four Decades Later.

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

July 23, 2018

The genetics of education

Filed under: Education,Genetics,Intelligence,Psychology — Razib Khan @ 11:49 am
Yale University

In the modern world, obtaining an education is a rite of passage. Not only does education provide one with skills useful for the modern economy, but it also helps to form one’s values and socializes one with peers who go through the same life experiences. Education isn’t just learning about various disciplines, it is a way to learn how to live in the modern world.

It is a topic which intersects with sociology, politics, and even ethics. As it turns out, education, or the attainment thereof, also intersects with genetics. This follows naturally from the first law of behavior genetics, “all human behavioral traits are heritable.” By “heritable,” geneticists refer to the fact that variation of a trait correlates with variation in genes. That variation tracks a causal relationship — so that genetic variants in some way cause a particular outcome.

This is easy enough to illustrate with an example. Imagine a genetic variant that changes the production of a biochemical that impacts whether someone is hyperactive or not. Hyperactivity is a behavioral characteristic with a lot of variables. Someone who drinks too much coffee will exhibit hyperactivity. But, it is surely true that some of the variation on these personality traits are due to cognitive neurological differences — some of which are then due to genetic differences between people. We may not be “born that way,” but we are probably “disposed to be that way.”

That’s a lot of caveats, and that is accounted for in the third law of behavior genetics: “a substantial portion of the variation in complex human behavioral traits is not accounted for by the effects of genes or families.” When it comes to behavior, environment matters. Although, what constitutes “environment” is not always clear, but any understanding of the genetic basis of behavioral variation needs to account for the fact that much of behavioral variation has nothing to do with genetics.

Galton’s classic illustration of parent-child correlation on height

And a when it comes to educational attainment, there is obviously no one “gene for education.” Whether or not you obtain a degree is impacted by many factors: from family encouragement and resources, inspirational teachers, intelligence, and your own conscientiousness. But, some of these characteristics, in particular the ones having to do with intelligence and personality, are impacted by your genes.

It has long been known through indirect methods that intelligence and personality are heritable. Identical twins are much more similar on these characteristics than conventional siblings, and relatives are much more similar than non-relatives. But, finding the biophysical genetic basis has been difficult because of the fourth law of behavior genetics: “A typical human behavioral trait is associated with very many genetic variants, each of which accounts for a very small percentage of the behavioral variability.”

A traditional way for geneticists to discover the cause of a trait is to target particular genetic locations and see if they are associated with the trait in question. This “candidate gene” method has been useful for many diseases, where a single defective mutation is responsible for much of the cause of the disease. But, it has been an utter failure in behavior genetics because of the fourth law of behavior genetics. To establish a connection between a genetic variant and a behavioral trait requires enormous sample sizes and a good knowledge of the human genome.

Until the year 2000, we didn’t have the sequence of a human genome, and until the past decade, dense assays of human genomic variation were expensive — this meant that studies were limited to small sample sizes and only a few genes. Most of the published results did not replicate, because they were not true in terms of the effect of the gene on the trait in question.

Recently, all that has changed. Thanks to “next generation sequencing” and “chip technology” researchers now have access to hundreds of thousands of markers in any given person — and cheaply at that. This cost-effectiveness allows for an increase in sample size; as many more people can be tested. This shatters the barriers implied by both the third and fourth laws of behavior genetics: small effect sizes no longer impede discovering ‘the needles in the haystack’ of complex traits. Bigger sample sizes and more subtle statistical methods are producing results that only a few years ago would have seemed fantastical.

A new paper in Nature Genetics illustrates this starkly, Gene discovery and polygenic prediction from a genome-wide association study of educational
attainment in 1.1 million individuals
. The authors identified 1,271 independent genome-wide-significant SNPs. This is a big achievement, considering that five years ago a paper with ~125,000 individuals identified just 3 SNPs that were significant for this trait!

Though it is hard to generalize about 1,000+ genetic variants, the figure to the left illustrates that the genes that these variants are found in are highly over-expressed in the nervous system. This is exactly what you see in most genetic analyses of complex traits that are behavioral. The genetic “hits” are found disproportionately in genes that control variation in neurological function because behavior is downstream of brain function. To be fair, many genes express in the brain, so that’s not a surprise. Rather, the authors compared the gene’s expression level to the typical gene.

Curiously these hits are not particularly over-expressed in genes associated with the development of glial cells, those cells in the central nervous system which are not neurons. Because these cells form the tissue which scaffolds the connections between neurons, the authors suggest that this might mean that differences in cognitive ability between individuals may not be a function of “transmission speed.” This highlights the fact that the these sorts of abstruse statistical analyses ultimately aim to uncover underlying biological phenomena.

And yet such a paper, with over 1 million samples from numerous cohorts, will have to get into the statistical weeds. One of the major issues that crops up in these analyses is “stratification.” This means that the genetic variation in the sample is correlated with variables such as geographical population structure. Therefore, some of the positive hits for any of these sorts of analyses might easily be picking up the overall population genetic variation and differences between groups, which may not have a genetic basis at all (e.g., British tend to drink tea, Americans tend to drink coffee).

Empirical genetic relationship of siblings

To get around this, the authors look at a sub-sample of 20,000 sibling-pairs. Many of the issues presented by population stratification do not apply within families. Families have the same broad genetic background, and also control for many environmental differences (since siblings are raised in the same family and socioeconomic context). But, there is still genetic variation among siblings, and some of this variation is responsible for variation in traits between siblings. After all, height tends to run in families, but the difference in height between same-sex siblings is not usually due to differences in nutrition (at least in the developed world).

Looking at the associations between genetic variation and educational attainment within families the authors found “that within-family
effect sizes are roughly 40% smaller than GWAS effect sizes.” In other words, there are factors that seem to result in the overestimation of the genetic effects on educational attainment within the broader population. The authors note that the same does not apply to height.

What might account for this then? One possibility is that some of the genes that a parent has, but does not transmit to the offspring, might result in a more beneficial environment. This is often termed the “parental effect.”

The paper looked are more than just educational attainment. With sample sizes in the hundreds of thousands they also looked at cognitive performance and mathematical ability (self-reported). Using the same methods as for educational attainment, the authors predicted around 10% of the variance.

Of course there are limitations. The sample size is large, but not diverse genetically. Overwhelmingly of European origin, the authors found that their method could predict less than 5% of the variance in African Americans. This is not surprising, because genome-wide associations often do not predict well across different populations.

Additionally, there is the reality that these methods focus on common variation within populations. The heritability of most behavioral traits using more indirect classical methods is much higher than this ~10% of variation explained would imply, so there is still a genetic component to be accounted for. Perhaps this variation is found in rare genetic variants, which are not explored in this sort of research.

Ultimately, we may look back at this 1 million-person analysis as the first in a scholarly tradition of massive GWAS sample sizes. Genomics is cheap enough that it is possible that genetic sample sizes in the range of a billion are feasible within 15 years. That will probably require a whole different set of esoteric methods but will probably yield many novel results.

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

The genetics of education 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.

History and genetics of the Han

Filed under: China,Genetics,History — Razib Khan @ 3:14 pm

About 20 percent of the world’s population lives in the People’s Republic of China.Taking their name from the Han dynasty of ancient China, they are the core ethnicity of the People’s Republic of China: making up about 90% of the total population. When the imperial system was overthrown by a republic in 1911, China was founded as a union of “five races.” They were the Manchu, who had previously provided the royal house, the historically important and ethnically distinctive Hui (Muslims), Tibetans, Mongols, and of course, the Han: who provided the common language of Chinese society and dominated its culture, civil administration, and military.

Shang Dynasty Chariots

The origin of the modern Han traces back to the mists of antiquity and prehistory. Chinese history is highly periodized; with a sequence of legendary dynasties which gave rise to those which were textually attested. This thematic arrangement of time is not a matter of conjecture or externally imposed frameworks, but rather it emerges out of the rich and elaborated native historiography. Like the Greco-Romans, the Chinese produced native annalists and observers galore.

China, as we understand it, began more than 3,000 years ago. During the Late Bronze Age, the centuries before 1000 BC, the Shang dynasty emerged as the paramount military group in the middle reaches of the Yellow river basin. With a ruling caste of chariot-riding aristocrats, the Shang seem much like the barbarian ruling houses of the Mycenaean world in lifestyle and outlook. Much of what we know about them can be ascertained only through archaeology or the commentaries and critiques of their successors: the Zhou. Because of their use of oracle bones as a form of divination, the Zhou still provide the first evidence of a state deploying literacy in East Asia. The distinct writing style of the modern Chinese has its roots in this place and time.

Eventually, the Shang fell to the Zhou. Originally a semi-barbarian state on the western fringes of the Shang state, the Zhou needed to be more cultivated than the Shang because they were arrivistes. The Zhou left a more substantial literary record as transmitted by their cultural heirs. It is from them that many concepts central to later Chinese civilization are inherited, such as the emphasis on the Mandate of Heaven in determining who ruled and who was ruled. The benevolent and upright character of men such as the semi-historical Duke of Zhou served as exemplars for Chinese elites for nearly over 2,500 years!

It was through Confucius and his acolytes that the influence of the Zhou echoed down through the generations, even into the 20th century. The imperial bureaucracy was steeped in a philosophy, which esteemed the Zhou as having presided over a Golden Age of righteousness and rectitude.

The First Emperor’s terracotta army

As the Zhou dynasty collapsed as a military power in the course of events over the first millennium BC, hundreds of philosophical schools proliferated across the landscape. Men who would have otherwise wielded the sword in service to their masters, took up the brush to paint and write out their thoughts. Martial codes of honor were transformed into rules to live a more pacific life by. These men, the shih, were the prototypes of the civilian scholar-officials who served as the model for the Chinese gentlemen throughout the whole period of the imperial system, from around 200 BC down to 1911 AD.

A class system, often honored in the breach, emerged in China during this period. The rulers and scholar officials were on top, and just below them were farmers: the producers of wealth. Under them toiled the the artisans, merchants, and soldiers. Strangely, this may reflect aspects of deep history.

While in much of the other half of Eurasia over the past 5,000 years has been characterized by the explosion of a few paternal Y chromosomal lineages, the Chinese population shows evidence of more gradual and consistent expansion; beginning with the rise of agriculture. Though the Shang ruled their domains from chariots, these tools of war came late to the East, and the Shang ascendancy was short-lived. The deep and broad growth of Y chromosomal lines across China suggests expansion from a small core group of agriculturalists, until the full expanse of North China was dominated by people speaking the Chinese language and practicing the Chinese culture.

As documented in a preprint from last year, a comprehensive map of genetic variation in the world’s largest ethnic group — Han Chinese, modern genetic variation within the People’s Republic between the Han of different regions is strongly conditioned on geography. Most of the variation is from the north to the south; far more than from the east to west. This may reflect the fact that until the Tang dynasty, between 600 and 900 AD, much of China south of the Yangzi river was inhabited by minority groups, such as the Dai and peoples related to the Vietnamese and the Hmong.

Meanwhile in the heart of early Chinese civilization, the Yellow river basin, many of the people exhibit the hallmarks of genetic influence from the people of the steppe, like the Mongols and even Western Eurasians. Between 200 BC and 200 AD, China was ruled by the Han dynasty: a culmination of the first period of Chinese cultural and demographic expansion and consolidation. After the Han collapse, however, much of North China was occupied and ruled by groups from the steppe. A mixed aristocracy of horsemen arose, and it was from this class there emerged the men who eventually reconquered all of China, from north to south, culminating in the Tang dynasty.

Buddhism flourished in China during the Tang dynasty

In the centuries before 1000 AD, the Tang pushed the center Chinese civilization from the north down to the Yangzi basin; engaging in reclamation projects and encouraging the planting of superior varieties of rice. If the people of northern China are the scions of the Han, those in southern China are children of the Tang.

As the second millennium after Christ began, the Chinese civilization and state occupied the broad expanse of eastern China that we know of today, from Korea along the edge of the sea and down to Vietnam, and deep into the interior. Whether noodle loving people in the north, or rice farmers in the south, they all spoke a dialect of Chinese, and were united by a written language. Though differences of region and class persisted, the meritocratic regime of scholar officials promoted by the new Song dynasty that succeeded the Tang bound the nation together, and took strength from a a revived Confucianism, which synthesized aspects of Buddhism — which had been introduced from the western regions.

But just as the Song were on the cusp of bringing shape to the China we know today, the Mongols under Genghis Khan and his successors first conquered the North China plain and later the Yangzi basin — and even the far South. The edifice of culture the Song built, the Mongols destroyed. China under the Song had promoted a meritocracy, and the Mongols placed themselves at the head of an ethnic a caste system determined by blood; where Muslims from Central Asia operated in the middle ranks as intermediaries above the subordinate Han majority. The Mongol rule was not for long, but after their expulsion and the reemergence of the Han under the Ming dynasty, the Muslim presence in China continued on as a long-term reminder of that era.

Hui Muslims

Today the descendants of these Muslims, the Hui, resemble the Han physically, and speak the Chinese dialect of the region in which they live, but practice Islam and eschew pork. Their East Asian physical appearance is a testament to the assimilative power of the Han, who absorbed various steppe peoples each in turn, though the cultural distinctiveness reminds us that China has long been connected to the rest of the world, and has changed with impact, from Buddhism to the Mongols and finally the adoption of Communism in the 20th century.

On the eve of the modern era, Jesuit astronomers were advising the Ming court, and the Chinese were conquered again by outsiders. Manchu people from the far northeast swept down and took city after city, until the last Ming emperor hurled himself into the South China Sea. And yet, just as captive Greece conquered Rome culturally, so the Manchus became for their Han subjects exemplary Confucian autocrats. The apogee of Imperial China came under the Qianlong Emperor, who presided over a decades long “Indian summer” of Han civilization in the 18th century… unaware of the specter of European colonialism on the horizon. Over the centuries, the Manchu separation from the Han majority became less and less a matter of reality (as opposed to a polite fiction). Today China is home to millions of “Manchu,” but the vast majority are difficult to distinguish from the Han of the north.

With more than a billion citizens today, China is a massive “natural experiment” in human demography. Hundreds of millions are on the move from the heartland to the glittering (and grimy) cities: mixing marrying with people they would otherwise never meet. Though lacking in the rich and deep genetic diversity of Africa, China makes up for it in raw numbers and a newly found focus on scientific advances — backed by a dynamic economy. The Chinese were expert chroniclers of their own history, so genetics will shed only so much new light beyond that. We already know the broad narrative because the Han remember and record.

Rather, the large potential upside of Chinese population genetics is in medical traits. The shock of the modern world and its consumer lifestyle, intersecting with the genetics of peasants farmers. Though specific results in China may not always be generalizable to the whole world, to some extent China is much of the world. The history of the Chinese past is vast and fascinating, but the possibility of the Chinese science of the future is tantalizing.

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

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

July 12, 2018

Running your own analyses

Filed under: Genetics,Population genetics,Scripts — Razib Khan @ 8:25 am

For the technically inclined people here: Tutorial To Run PCA, Admixture, Treemix And Pairwise Fst In One Command.

July 10, 2018

Ancient Ancestral South “Indians” may have roots in Southeast Asia

Filed under: Genetics — Razib Khan @ 10:51 pm

At the Society for Molecular Biology and Evolution conference in Japan there is a presentation which reports evidence for gene flow from Pleistocene Southeast Asians into South Asia. I have long suggested this was possible for several reasons.

During the Last Glacial Maximum ~20,000 years ago Southeast Asia would have been a relatively protected and well-watered region in comparison to South Asia. My understanding is that moist savanna has higher population densities of hunter-gatherers than dry scrubland. Southeast Asia would have had a great deal of the former, and almost none of the latter (the LGM was drier, and the rainforest zone in Southeast Asia would have been smaller, and Sundaland was probably mostly savanna). The Thar desert zone would have been much more expansive, pushing south and east. The summer monsoons were far weaker.

All this indicates Southeast Asia would have had larger populations than South Asia during this period. And large populations tend to impact smaller populations genetically.

Additionally, looking closely at haplogroup M, which is highly diverse in South Asia, some of them look to be intrusive and related to branches in Southeast Asia. Though I do believe some of the M branches in South Asia are very old and probably native, others may have been brought by Southeast Asian people related to the Hoabinhian culture (which was mostly absorbed by rice farmers from the north during the Holocene).

During the Pleistocene Southeast Asia and Southern Asia were probably part of the same biogeographic zone, just as they are today. The ancestors and relatives of the Negrito peoples of Southeast Asia probably displayed a continuity from South Asia down toward Oceania. The preponderant gene flow at some points from the east to the was probably just a function of population size and climate.

Today the genetic differences on the border between South and Southeast Asia are striking. Though Pathans and Punjabis are quite different, they are far closer genetically than Bengalis and Burmese (notably, linguistically the chasm is also far greater). I think that has partly to do with agricultural and sedentarism. The mountainous zones in northeast India and western Burma are far harder for farmers to traverse than small groups of hunter-gatherers.

July 9, 2018

Bangladeshis are very East Asian, Sri Lankan Tamils are not quite as structured

Filed under: Genetics — Razib Khan @ 11:38 pm
Click to enlarge

A very long post as my other weblog where I reiterate how East Asian Bengalis, and in particular East Bengalis, are. Aside from the existence of a Dalit/scheduled caste subcommunity, very little has surprised me about Bangladeshi genetics in the last 5 years or so. Rather than a novelty, some simple truths seem to be reinforced over and over. Two major takeaways:

1) the only “exotic” aspect of Bengali ancestry is that Bengalis are substantially East Asian (with the exception that this is sharply attenuated in Brahmins).

2) Though there is some evidence of West Asian admixture in a few Bengali Muslims, you have to look really close to see evidence of it. Though I can believe and do believe, that many Bengali Muslims have a genealogical connection to Iran and Turan through a distinct paternal lineage, that has left a minimal genetic impact.

But one thing I did not emphasize in the post: looking closely at the 1000 Genomes Sri Lankan Tamil samples from the UK I think it is clear that they are less structured than an Indian sample would be. The proportion of Dalits is far lower than in the Indian Telugu sample obtained from the UK. So I will have to update my assertion that the Sri Lanka Tamil sample is as structured as Indians. It isn’t. This is contrast to the Lahore Punjabi samples, which are highly structured. More so than the Sri Lanka Tamils.

July 4, 2018

American folkways & American pedigrees

Filed under: American History,Genealogy,Genetics,History — Razib Khan @ 11:35 am
St. Augustine Historic district

Over ten thousand years after the first Americans settled the New World, from the Arctic to Patagonia, a new people arrived on these shores. From “deep history” to colonial history. Before Plymouth, before Jamestown, even before Santa Fe, there was St. Augustine, facing the Atlantic on the Florida coast. Occupied continuously since 1565, St. Augustine is the oldest current city in the continental United States.

This small and obscure town has witnessed massive culture, political, and demographic changes wrought over the continent of North America across 450 years from the fringes. Its existence reflects a tentative and tenuous phase in the exploration of North America by Europeans. Though inauspicious, the fact that St. Augustine sustained itself on the edge of North America for centuries is a testament to something different that was looming on the horizon.

Sir Walter Raleigh

Of course the dominant culture and people in the continental United States by 1800 was not that of the Spaniards of Florida or New Mexico. Rather, it was from the British Isles. The two primary early zones of British settlement were in the Chesapeake and Massachusetts Bay areas. These were the core regions around which the Commonwealth of Massachusetts and Commonwealth of Virginia developed.

By the last quarter of the 18th century the entire eastern seaboard of North America was dominated by settler colonies of diverse European provenance.

In New England, Massachusetts had been joined by colonies which were offshoots in various ways from the founding stock that coalesced around Boston. The 50,000 or so English settlers of the middle of the 17th century were now 750,000 New Englanders, due to natural increase driven by the fecundity of its people. Similarly, to the north in Canada the original small number of French who settled on the margins of the vast coniferous forests in search of furs and other riches had flourished and grown into a fully-fledged society, which even maintained itself in the face of British conquest and domination, strong their Roman Catholicism and fiercely devoted to their language.

In Virginia the younger sons of English nobility and the descendants of indentured servants had recreated an aristocratic society characterized by hierarchy and inequality typical of southern England on American shores. While the settlers of New England brought their Reformed Calvinist faith and its sectarian offshoots to the New World, seeking freedom to worship as they wished, the grandees of the Tidewater adhered nominally to the Anglican Church, and focused their energies on increasing their wealth and prestige. The kingdom which they wished to inherit was in this world, not the next!

Slaves cultivating tobacco in Virginia

Much of the wealth of the kingdom which the planters were building unfortunately consisted of slaves. The ancestors of black Americans arrived mostly in the 17th and 18th centuries. Though importation of slaves was legal almost into the 19th century, the reality is that the vast majority of the ancestors of black Americans date to a far earlier period. Because slave fertility was above replacement, the American trade in humans quickly become independent of international sources. The first person killed in the Boston Massacre was Crispus Attucks, a man of African and Native American ancestry, who was as American as American can be.

Along with Puritans, and the Southern planters and the slaves, on the eve of the Founding of the United States of America numerous other societies had developed organically from very different seeds. Dutch New Amsterdam had become New York by the Revolution, but the entrepreneurial spirit of the Dutch republic persisted, as the great port remained an ethnic melange driven by commerce, not the whims of aristocrats or the will of God. Further south, the great city of Philadelphia was founded by industrious English Quakers, but these were joined by German Protestants and people from Ulster and the border region between Scotland and England, the “Scots-Irish.”

Wyckoff House in Brooklyn dates to the Dutch period

Though Philadelphia was the destination for the hundreds of thousands of Scots-Irish fleeing deprivation in their homeland, they did not tarry long, pushing deep into the back-country of Pennsylvania, and then migrating south along the ridges of the Appalachians. Where planter class established an aristocratic society of elites whose privileges were built on the backs of poor whites and black slaves, the rugged uplands of the vast southern stretches of the English colonies were populated by an individualistic and egalitarian people whose wealth was measured in their pride.

President Andrew Jackson, the son of Ulster migrants

These were the people caught up in the American Revolution, on both sides, rebel and loyalist. Despite their Northern European origins, with the exception of the black slaves, they were still a diverse motley. Thirteen separate and distinct colonies with many local subcultures. Not a single nation.

There were numerous waves of people who arrived after the British colonies became the United States of America. Irish and Germans in the decades before the Civil War transformed the culture of the United States of America, with their Catholicism and their beer, not to mention triggering an anti-immigrant populist movement which has resonances down to the present day.

After the traumatic conflict between the North and South, immigrants arrived in large numbers as industry began to demand labor in the cities and the vast open expanses of West needed to be settled. Scandinavians, Southern and Eastern Europeans in the decades around 1900 congregated in the cities of the East and Midwest and worked in factories and planted farms deep on the Great Plains. From the Far East there even arrived Chinese to build the railroads and operate the mines across the Pacific coast. The racial resentment of these Chinese led to explicit bans on immigration from Asian countries for decades.

Despite all this immigration, even as late as 1990 50% of the ancestry of the population of the United States of America was derived from those who were present and counted by the Census of 1790.

Though there are numerous interpretations and debates about American history, one thing that is clear is that it is a history of which we have copious records and documentation. The Founding Fathers are not dead names, but people who come alive in their correspondence. By the middle of the 19th century the immigrants who came to these shores are also visible in all the realism of their features through the magic of photography. Documents at Ellis Island mean that genealogical detective work can yield insights which illuminate the understanding of many a family’s past.

Irish immigrants

And yet genetics can shed light on historical patterns. Unlike written text genetics is neutral. It does not present a particular narrative or agenda. Though the tale genetics tells is that of the winners, there is no hiding this truth. In genetics the future belongs to those who procreate, and that is the foundation on which its logic is built.

Modern genetic technology surveying hundreds of thousands of markers in the human genome allow researchers to reconstruct pedigrees, family trees, and mark the history of peoples through their descent. While ancestry tests usually focus on deep history and ancient evolutionary and population events, modern genomic techniques allow for the exploration of events even within the last few hundred years.

Several years ago the genetics arm of Ancestry looked in their database, and selected 770,000 individuals of American heritage to analyze.

By surveying the patterns and clusters of relatedness, the researchers constructed a map which shows that most genetic variation in the United States is between the north and the south. That is, people from New England tend to be more different from people from the Deep South, than they are from those from neighboring states. In fact, the largest component of variation tracks geography very well, from northern New England, down to the Mid-Atlantic, then to the South.

The second component of variation tracks east to west, the direction of the migration of settlers. Very few people left Massachusetts for Mississippi. Many did leave Massachusetts for Michigan.

Those who pulled up stakes were not always the same sort of people who stayed home. So over time Westerners became somewhat distinct from Easterners. Those who left married others who left. Those who stayed continued to marry others who stayed.

Citation: Clustering of 770,000 genomes reveals post-colonial population structure of North America
And yet the reality is that different regions of the West were settled from different regions of the East.

The genetic clusters present some interesting results which are comprehensible only through the lens of history. Hawaii and Utah are two states which are a bit skewed to the north. But as it happens these are states which were heavily settled by New England Yankees. In contrast, though states such as California might be dominated by cosmopolitan cities such as San Francisco and Los Angeles, in the hinterland are many people whose roots are in the uplands of the South. Scots-Irish who traveled west in search of greener pastures, who brought their music, twang, and kinfolk.

Geographic patterns of genetic clusters

While Indiana was settled mostly from the South, there were far more Yankees who founded towns in Michigan and Wisconsin. Meanwhile, Ohio and Illinois were both divided between a northern portion settled from New England, and a southern expanse dominated by Scots-Irish “Butternuts.”

All this seems clear in the genetic results. Now we can quantify the differences. Illinois is tilted a bit to the northern migrants. Ohio somewhat to the southern ones. Historical debates can be resolved through genetic analyses!

Over the next few years tens of millions of more Americans will obtain direct to consumer genetic tests. The database will grow larger and larger. Many demographic questions related to the history of this country will not need to be explored through reconstruction of texts and laborious perusal of letters and court documents. Rather, scientists will simply scan through the pedigrees they construct from human genomes, and synthesize their results with the rich assortment of resources already available from the fields of genealogy and history.

A nation of immigrants and settlers will become an open book to all who wish to read their incredible stories.

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

American folkways & American pedigrees was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

July 3, 2018

Bhadralok are made not born

Filed under: Genetics — Razib Khan @ 10:53 pm

Tanushree Dutta is a Bengali Kayastha

I have two samples of full ancestry from West Bengal. A Kayastha and a Brahmin. You can see where they plot.

Bengali Brahmins are very similar to North Indian Brahmins (often they have some “eastward” shift). In contrast, the Kayastha individual looks like the Bangladeshi samples, except with far less East Asian ancestry.

I do want more samples. Though I’ve gotten a few Bengali Brahmins and they exhibit the sample pattern as above. I am curious about non-Brahmin West Bengalis. But from the above, I think I will conclude that the hypothesis that Kayasthas are a cultivator caste which uplifted themselves occupationally is probably the right one.

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.

South Asian Genotype Project, Summer 2018 Update

Filed under: Genetics — Razib Khan @ 7:38 am

Just an update on the South Asian Genotype Project.

It seems Brahmins from Maharashtra are like Brahmins from South India. Brahmins from Gujarat are like Brahmins from North India.

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.


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.

June 13, 2018

The days of the All-Fathers

Filed under: Father's Day,Genetics,History — Razib Khan @ 11:12 am
Citation: Zerjal et al.

“A man’s greatest joy is crushing his enemies.”

— Genghis Khan

There are many apocryphal quotes attributed to Genghis Khan. And there’s a reason for that — in a single generation he led an obscure group of Mongolian tribes to conquer most of the known world. His armies, and those of his descendants, ravaged lands as distant as Hungary, Iran and China. After the great wars, though, came great peace — the Pax Mongolica. But the scale of death and destruction were such that in the wake of the Mongol conquests great forests grew back from previously cultivated land, changing the very ecosystem of the planet.

It is no great surprise then that if there were ecological impacts of the Mongol conquest, there were also genetic ones. About ~10% percent of the men who live today within the former territories of the Mongol Empire at the death of Genghis Khan carry a particular Y chromosome lineage. About 15 years ago researchers tried to assess the relationship of these individuals on their Y chromosome, and were confronted by the reality that there wasn’t any neat relationship…the phylogeny was a “star.”

Citation: Zerjal et al.

What this means is that at some point in the past men who carried this Y chromosome underwent a very rapid expansion. So rapid that the genetic tree simply “explodes,” rather than accumulating mutations in a gradual manner which could outline different relationships between parental and offspring Y chromosomes. By looking at the pattern of diversity of the branches of the star lineage scientists concluded that this cluster must have expanded about ~1,000 year ago in the past.

Genghis Khan

What happened about ~1,000 years ago? It is notable that the lineage, the “star haplotype,” is most diverse and frequent in and around Mongolia. The conclusion was unmistakable: this Y-chromosome lineage comes down from the tribe of Genghis Khan, and its explosive growth occurred due to the explosive growth of the Mongol Empire.

Genes reflect history and social norms. The history of the Mongol expansion and the extermination of local elites across vast swathes of Inner Asia has left its legacy in the genomes of modern people, with the signature of explosive growth in the Genghis Khan Y haplotype, which stretches far and wide. The persistence and frequency of this lineage across nearly 1,000 years attests to the social prestige attached to be a direct male scion of Genghis Khan and his descendants.

The cultural importance of descent from Genghis Khan in Inner Asia can not be underestimated. Though he was a pagan through-and-through, among Muslim Turkic peoples descent from him became highly prestigious, and a mark that one was meant to rule.

Citation: Karmin et al.

In the case of the the Genghis Khan Y lineage there is a historical record that explains the cause of the genetic phenomenon. What about other Y-chromosomes?

It turns out that about 4,000 to 5,000 years ago a widespread bottleneck followed by an expansion occurred specifically on the Y chromosome for many lineages, not just one. This is particularly true of Eurasia.

For example, Y haplogroups R1a, R1b and I1 seem to have undergone expansion at this time after a population reduction. R1b is the most common haplogroup in Western Europe. R1a is the most common in Eastern Europe, Central Asia, and much of South Asia. I1 is the dominant haplogroup of Scandinavia. But 5,000 years ago ancient DNA tells us that R1a ad R1b were very rare where today they are common. I1 seems to be a relic of the Pleistocene hunter-gatherers of Europe, but it only began expanding at the same time as R1a and R1b.

Unfortunately 5,000 years ago most of the world was cloaked in prehistory.
Light war chariot

History provides few clues about why a few Y chromosomal lineages came to be so dominant. But we do know that this was around the time when pastoralism and horse-powered warfare, in the form of the light chariot, came into being. New research suggests that only theoretical models that rely on “inter-group competition” can explain the Y-chromosome pattern we see. That is, it can’t be polygyny, where a few men have many wives within the tribe. Rather, it has to be a tribe as conceived of as a patrilineal kinship unit. The victory of one tribe was total loss for the males in another tribe, and each tribe was represented by a particular Y-chromosomal lineage.

Which sounds awfully familiar to the descendants of Genghis Khan…

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

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

June 11, 2018

Genetic variation in South Asia

Filed under: Genetics — Razib Khan @ 1:33 am

I don’t have too much time right now. So a quick data post. The map above shows India’s scale in relation to Europe.

Below is an NJ tree that shows pairwise Fst values (genetic distance):

Please notice the small genetic difference between Britain/Spain/Poland. Compare to Gujrati vs. Sindhi, let alone Gujrati vs. Telegu.

Now, PCA:

Genetically Sindhis occupy a place between South Indians and Iranians. Some Gujaratis are nearly where Sindhis are, but many are far more shifted toward South Indians. The Fst display masks this since it aggregates populations.

Treemix shows the relationships and their scale. South Asians have a lot of drift between them.

Some of you are probably bored by this post and wonder about it’s practical implication. If so, keep on paging down (or up).

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