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February 14, 2019

Love, oxytocin and evolution

Filed under: Evolution,love,oxytocin,science,valentines-day — Razib Khan @ 1:52 am
Gibbons form pair-bonds

On some level, most scientists would say that everything is reducible to material and mechanism. But to say that “everything is due to the swerve of atoms” doesn’t get us much further than the ancient Greeks, who were the first to elaborate on such materialist ideas philosophically.

At the other extreme from scientists are those humanists who assert that concepts such as “love” or “hate” are not reducible to scientific analysis and decomposition. In this framework, love and hate are both emotions which exist in a particular social and cultural context, and general systematic analysis may miss the forest from the trees.

But if physics does not offer answers beyond the trivial, a better understanding of behavior or mental characteristics can be obtained by looking at sciences such as cognitive neuroscience and evolutionary biology, which exist at a higher level of phenomenological complexity. Behavior comes from the mind, and the mind is an expression of the brain, which itself is shaped by evolutionary pressures.

Romantic love as an emotion then exists in the context of our evolutionary history, and that history likely has something to do with mating and pair-bonding. Our “reproductive fitness” is conditional on the very act of mating, and often survival is dependent on aid and help from others. For birds, monogamy is so common because both parents are often required to warm and tend to eggs. In mammals, in contrast, males tend to be less involved in provisioning for offspring. But there are exceptions.

An “alpha couple” among wolves

Wolves, and some primates such as gibbons and humans, tend to be monogamous. This is evident in the minimal difference in the size between the two sexes, as well as genetic data which shows that the “effective population size” of males and females over time has been in the same order of magnitude. That is, a reasonable proportion of both males and females contribute genes to the next generation.

Humans have extended childhoods

One reason that humans have elaborate emotions related to bonding seems to be that our childhoods are extremely long. This means that parents, and in particular the mother, develops a strong bond to their offspring, which is reciprocated. In the complex social systems of our species feelings of connectedness extend to kinship, and the bond between mates is solidified with romantic love and companionship. Love comes in many forms in our lineage, but it is clearly a feature and not a bug.

This is ultimately a consequence of genetics. The tendency toward prosociality and empathy seem to be heritable. That is, some of the variation of the characteristics within a population is due to variation in genes. This is clearest in prairie voles, where different species exhibit radically different behaviors in relation to bonding and mating, and also different genetic profiles.

Individuals with more “G” allele have more empathy

In humans, the neuropeptide oxytocin has been implicated in variation in characteristics such as empathy and bonding. This research began with relatively small samples, but a recent study with 1,830 individuals reports a single mutation with the OXTR locus is associated with variation in empathy. This is not entirely unreasonable in light of the fact that in the modern human population there are differences in personality, and dispositions, including empathy. The persistence of various personality types indicates that there’s no singular way in which one maximizes long-term fitness, but many alternative strategies (within limits).

Romantic love in terms of its biological basis may have a fundamentally material and evolutionary origin: a tight bond between parents results in a greater likelihood that offspring grow up to adulthood. It emerges from a complex set of neurobiological pathways, which themselves vary due to genetic factors from person to person.

But just as sugar is a molecule we understand but find still delicious, so the sweetness of love remains even after unmasking the underlying science.

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


Love, oxytocin and evolution was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

February 12, 2019

Why Charles Darwin matters

Filed under: darwin,Evolution,science — Razib Khan @ 2:11 am

Charles Robert Darwin was born on February 12th, 1809. He was the son of a prosperous and prominent lineage. His grandfather, Erasmus Darwin, was a physician and public intellectual. Like his more famous grandson, the elder Darwin was a natural philosopher who propounded theories of evolution. On his mother’s side, Charles Darwin was the grandson of the manufacturer Josiah Wedgewood. If Erasmus Darwin reflected the intellectual currents of England during the late 18th century, Wedgewood illustrated the rise of the merchant class with the industrialization of Britain.

Growing up in comfortable circumstances, Charles Darwin had many opportunities to succeed, or fail. His university career was checkered at best. At one point it seemed likely that he would become a clergyman in the Church of England, satisfying his interest in the natural world as an avocation.

Life had different plans for him. He famously went on a voyage around the world, and his observations of the geology, flora, and fauna, fed into his later theories. But the truth is that the immediate consequence of Darwin’s travels was a book, The Voyage of the Beagle, which made him something of a minor celebrity in Victorian England. Even without The Voyage of the Beagle his name would likely have been noted in the pedigree of the prominent Darwin-Wedgewood family.

If Charles Darwin had never published The Origin of Species, history would have remembered him, albeit as a minor figure of the 19th century.

But Darwin did publish The Origin of Species. And after this, he published other books, most famously The Descent of Man. But Charles Darwin’s fame rests primarily on a single book published in 1859, whose full title was On the Origin of Species by Means of Natural Selection, or the Preservation of Favoured Races in the Struggle for Life.

Charles Darwin the man led a fascinating and full life. His lineage was colorful, his times were exciting, while his marriage was loving and passionate. Charles Darwin had enough texture and tension within his life that feature films can easily revolve around him as a character. He was a man in full.

But we are talking about Charles Darwin today because of the science which he assembled and presented within The Origin of Species. Though evolutionary ideas had been around since the time of the ancient Greeks, it was Charles Darwin who brought the idea to life through a plausible, compelling, and ubiquitous dynamic and underlying mechanism in the form of adaptation through natural selection. There were earlier evolutionary thinkers in the 19th century, but the reason that we use the term “Darwinism” interchangeably with evolutionary biology is that the model presented in The Origin of Species laid the foundation for the whole scientific discipline.

Science is not a single idea. It is not a hunch. It is the assembling of observations, the construction of theory, and the generation of predictions. With Alfred Wallace, Charles Darwin presented to his contemporaries the hypothesis that natural selection was the motor which drove the riotous diversification of form and function around us in the living world.

The development of genetics as field after 1900 revived Darwinian evolutionary biology as the study of the process of natural selection became a core element of the field of evolutionary genetics. Though others had proposed the tree of life and common descent, it was Darwins’ ideas of how that tree diversified which transformed what had been a stale description into a dynamic representation of what we now call evolutionary process.

It is true that despite the fertility of his mind many scientists today within biology do not read Darwin’s original works. But that is because his conjectures and certainties are laced through fields, part, and parcel of the axioms which are taken for granted by working researchers.

Today all biologists implicit stand on Darwin’s shoulders to see further and more clearly.

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


Why Charles Darwin matters was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

January 30, 2019

How ancient DNA illuminated the dark cave

Filed under: Ancient DNA,Paleoanthropology,science — Razib Khan @ 9:23 pm

Unfortunately, we do not have a time machine, nor is there any likely possibility of any such thing in the near future. The laws of physics are what they are. That is why those of us who are interested in the human past must make recourse to disciplines such as history, archaeology, and paleontology.

But all of these have their limits. History’s reliance on the written text means that there is a bias toward the records of the powerful and privileged because for much of history writing was the purview of elites. Archaeology focuses on material remains and artifacts, but there is only so much insight one can squeeze from pottery shards. Finally, paleontology must rely on bones which are very rare and do not provide a fully-fleshed picture of human life (literally!).

Of course, these methods improve over time. The decipherment of cuneiform in the 19th century opened up the pasts of the Babylonians, Akkadians, and Sumerians. In the 1950s the decipherment of Linear B meant that historians could confirm that the Mycenaean peoples of the Bronze Age were Greek-speakers. Radiocarbon dating transformed the ability of archaeologists to produce chronologies of cultural change over time at any given location with incredibility certainty. Finally, paleontologists have been able to utilize modern technology to “scan” fossils and so obtain much more information from any given sample than was possible in the post.

Into this landscape stepped ancient DNA. Analysis of genetic remains and material dates back to the 1990s, pioneered by Swedish paleogeneticist Svante Pääbo. But Pääbo’s work really came to the attention of the mainstream when his team sequenced the whole genome of a Neanderthal in 2010. Consider how amazing this is in light of the fact that the draft of the first human genome was only completed ten years earlier!

And it turned out that the Neanderthal genome had surprises in store for paleoanthropologists which they had not anticipated. For decades the relationship between Neanderthals and modern humans had been debated. The primary question being whether the former were ancestors of the latter. Or not, as was the orthodoxy in 2010 in much of paleoanthropology!

Pääbo himself held to this orthodoxy, and earlier work sequencing the mitochondrial DNA passed from mother to daughter, confirmed that Neanderthals were distinct from modern humans. No modern humans seem to carry a Neanderthal mitochondrial lineage. Case closed.

But the data had other plans. When the researchers compared the genome of the Neanderthal to that of modern humans, they found that modern humans were very different. This was to be expected. But, they noticed a peculiarity in the relatedness: modern humans outside of Africa were all somewhat closer to Neanderthals than modern humans within Africa. Assuming that modern humans descend from a population that expanded out of Africa relatively recently, the most plausible explanation for this pattern is that some of these non-Africans mixed with Neanderthals in their migration outward.

Denisova Cave

The ancient genome changed everything because now there was a definite benchmark for comparison, rather than all the indirect attempts that had been performed in the past. The ancient DNA was a game changer, confirmed by the finding later that year that remains from Denisova cave in Siberia belonged to a previously unknown lineage of human, closer to Neanderthals than modern peoples. It turns out this mysterious population also contributed ancestry to the peoples of Papua New Guinea, far to the south and east. So a single ancient genome transformed our understanding of the past, and shed light on patterns in the present.

Now, it isn’t as if geneticists were not using their techniques to make inferences about the past for decades. The “Out of Africa” model rested on genetic inferences, looking at variation in living people, and concluding from that that the ancestry of modern humans likely derives from an ancient African population. At such a broad level a method which relied on modern variation was sufficient. The results have held up. But when it came to narrower questions the methods which looked at the “tips” of the phylogenetic trees, the extant populations today, have been far less successful.

We know this because ancient DNA from the past 40,000 years has shown that there were massive population turnovers and mixtures all across the world. Using modern DNA to make projections of the past rely on assumptions of geographic stability of human groups…which turn out to be wrong. If one thinks of the human past as a phylogenetic tree, ancient DNA allows one to fill in “nodes” upstream of the “tips” of the tree. This resolves ambiguities, confusions, and corrects for mistakes in assumptions.

Ancient DNA cannot tell researchers “who” a people were. What language they spoke. Or how they lived. What it can tell you without debate is how people were related to each other in the past, and how they are related to people today.

We know, for example, that very few of the ancestors of modern Europeans derive from the people who drew the enigmatic cave paintings of the Upper Paleolithic. We also know that no modern people descend from the Cro-Magnon bands who replaced Neanderthals in Europe. These artistic creations are in some meaningful way the true legacy of these lost peoples.

Humans are one of the most mobile mammals, occupying six of the seven continents by 10,000 years ago. The tools, the technologies, of ancient DNA are another quiver in the arsenal of prehistorians. The migration of peoples is not everything, but it is an essential thing because without migration we wouldn’t be the most successful large mammal of the past 60 million years.

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


How ancient DNA illuminated the dark cave 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 12: The New York Times takes on Ancient DNA

Filed under: anthropology,DNA,Genetics,science — Razib Khan @ 3:42 pm

The Insight Show Notes — Season 2, Episode 12: The New York Times takes on Ancient DNA

This week on The Insight (Apple Podcasts, Stitcher and Google Podcasts)we discussed the controversy that has erupted over a 12,000-word piece in The New York Times Magazine, Is Ancient DNA Research Revealing New Truths — or Falling Into Old Traps? Many researchers associated with this work, including the primary focus of the article, David Reich, have taken issue with the reporting. We talk to Bastien Llamas, a researcher in Australia who has worked with Reich and is involved in the field of ancient DNA himself and been vocal on Twitter about the piece.

Much of the discussion is hard to understand without reading the piece in The New York Times Magazine, but also David Reich’s new book, Who We Are And How We Got Here, also helps.

As Bastien makes clear, the field of ancient DNA has gone from basically nothing to thousands and thousands of samples in less than a generation. But, we talk about the fact that a single whole-genome sequence has enough information to infer the history of a whole population.

In the piece, there is a reference to the fact that some labs seem to have technological monopolies which exclude other research groups. Bastien outlines exactly and in detail the “other side” from the perspective of Svante Paabo.

We also discuss the debate around the peer-review of a paper on the genomics and history of Vanuatu, and how the “full story” is more complex, nuanced, and different, from what you might take away from simply reading the piece.

There was extensive discussion about the different technologies utilized in the field of ancient DNA, in particular, “shotgun whole-genome sequencing” vs. “SNP-capture array.” The technological debate is embedded in the reality that the field to a great extent is an oligopoly, with a few big labs and consortiums dictating the direction of the research questions and methodologies. We talk about this reality, as well as the nature of science now and the possibilities of the future.

The New York Times Magazine also takes for granted the idea that David Reich and colleagues are resurrecting old racist theories about the migrations and replacements of peoples, which archaeologists rejected after World War II due to their ideological valence. But an anthropologist points out that this is not actually what happened, and that the change from “cultural-history” to “processualism” had as much to do with the data available and scientific fashion as it did with broader cultural currents.

Finally, we discussed working in Australia and future directions in ancient DNA.

If you want to get a more academic understanding of the field, please see this opinion in PNAS, To curate the molecular past, museums need a carefully considered set of best practices.

David Reich’s lab website has two updates relating to the article.

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 12: The New York Times takes on Ancient DNA was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

January 22, 2019

Humanity is smarter than the sum of its individuals

Filed under: Culture,science — Razib Khan @ 10:46 pm

We live in a world of wonders. Airplanes take us across the world, computers connect us digitally, and antibiotics cure us of infections. But how does any of this work? Do you know? Does your neighbor know? Billions of humans beings use mobile telephones. But could any single human build a mobile telephone from scratch? Could they even repair their phone if there was a defect?

The answer is obvious. A single human being, no matter how smart, is likely to be able to create a smartphone. A single human being is not able to master all the disciplines, from software engineering to solid state physics, that would allow them to design such a device in the first place. And a single human being does not have access to the specialized and efficient economic system that allows for the production of modern technology. The mobile telephone is the product of a system.

In our current age, we are wont to chalk this up to the interdependent economics of an advanced society. Everyone specializes, and complex supply chains interact dynamically through the “invisible hand,” to provide for us incredible productivity gains. But the truth is that this is how it has always been for our species.

Imagine being asked to create a bow and arrow. A functional clay pot. Or raise a crop of wheat. Though none of these things are highly “advanced” technologies, individual humans without specific skill would be at as much a loss as if they were asked to build a car from “scratch.” Specialization, compartmentalization, and almost miraculous social coordination has been part of our species’ toolkit since the beginning. It was true during the Middle Ages. During the time of the Roman Empire. And during the Stone Age.

Humans may have very large brains for our body sizes, but the truth is that our brains have been about the same size for the past 200,000 years. And yet our innovativeness did not stop 200,000 years ago. Rather, the rate of cultural innovation has increased over time, despite the fact that individual humans have had the same hardware. If human cultural complexity is due to the size of our brains, it is curious that our brains have not changed while our culture has. Something else is going on.

Human cultural evolution operates not simply through shaping our biology in the form of our brains but embedding in social memory a distributed set of skills and abilities which develop cumulatively over tim

Human societies are “hive minds,” and even if individual constituents of that hive mind have not changed for many millennia, the mind itself has been evolving over time. Adapting and reshaping itself. The distributed network has allowed for the development of specialized individuals with particular skills.

A few hundred years ago the vast majority of humans were farmers. Today, one occupation is not dominant, and most people fill specialized niches. As individuals, we lack the general flexibility of our Paleolithic ancestors. Take us into the wilds and many of us perish. But as a social unit, we are far more advanced because the “memes” that have come to define us at the level of societies are far beyond anything our ancestors had access to.

No single human being was responsible for getting our species to the moon. Rather, the collective wisdom of our species was responsible, across the world, and going back in deep in time.

Though evolution in a genetic since has continued since the Paleolithic and continues today, perhaps the most riotous explosion of evolution in the past 10,000 years has been culture, not biological!

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


Humanity is smarter than the sum of its individuals was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

January 16, 2019

How your Neanderthal functions in the human genome

Filed under: Human Evolution,Neanderthals,science,Selection — Razib Khan @ 2:28 pm

What does it mean that you have Neanderthal ancestry? Everyone agrees now that that ancestry exists, but does it make you any different from what you’d be otherwise? From a scientific perspective, one might ask what the function of Neanderthal genetic variants are. What do they do in your body?

The truth is that they do many things. The human genome has many genes. About 20,000. Across those genes, there are ~3 billion base-pairs. A, C, G, and T. The best estimate if you are not African is that there is a 1–2% chance that a base is from a Neanderthal ancestry. Modern humans don’t have the same 1–2%, so around 30% of the Neanderthal genome can be reconstructed from living people alone!

For many years researchers have examined patterns of Neanderthal admixture within the genome, and over time (looking at ancient DNA). Because the ancestors of Neanderthals separated from modern humans 700–900 thousand years ago, there are some genetic incompatibilities, and Neanderthal variants are likely to be selected against. The most recent research, though not the final word, indicates that much of this selection happened very early on.

In other words, most of the very incompatible Neanderthal variants were removed from the human genome within ~10,000 years of the admixture.

But within the genome, there are differences as to where Neanderthal genes are found. Early work indicated that Neanderthal ancestry was overrepresented in the vast majority of the genome that does not code for proteins (“junk DNA”). This was suggestive of the likely that Neanderthal ancestry was usually bad when it coded for proteins.

Today a closer look, as implied in the figure the left, suggest that selection against Neanderthal variants was less about protein coding, and more about regulation. Though the human genome has only about 20,000 genes, how those genes are expressed in tissues, and how they are expressed, plays an essential role in differentiating us from other mammals. This is why the vast majority of our genome can be similar to a chimpanzee, or a Neanderthal, and yet modern humans are creatures very different.

It may turn out that our unique Neanderthal ancestry may play a greater role in rearranging how genes express themselves more than anything else.

Discover your Neanderthal story today!


How your Neanderthal functions in the human genome was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

January 7, 2019

Toward a mature conservatism

Filed under: science — Razib Khan @ 1:51 pm

India scientists dismiss Einstein theories:

In 2014, Prime Minister Narendra Modi told medical staff at a Mumbai hospital that the story of the Hindu god Ganesha – whose elephant head is attached to a human body – showed cosmetic surgery existed in ancient India.

In 2014, Prime Minister Narendra Modi told medical staff at a Mumbai hospital that the story of the Hindu god Ganesha – whose elephant head is attached to a human body – showed cosmetic surgery existed in ancient India

I don’t comment much on Indian politics for two reasons. First, I think macroeconomic conditions and trajectories are more important than politics as such for a developing nation like India. Second, the details of the cultural and political dynamics within any given nation are really hard to grok from the outside.

That being said, the widespread percolation of this sort of pseudoscience and pseudohistory on the Indian Right is a problem and has analogs with instances in other nations (e.g., Mike Pence is almost certainly a Creationist). These beliefs are often (though not always) harmless in and of themselves, but they are indicative of deeper maladies in terms of epistemological hygiene.

I have Hindu nationalists who are broadly on the same empirical page as me. We differ on details of values and emphases. And I know they are somewhat embarrassed by these weird ideas about nuclear weapons in ancient India. The key is to keep a lid on it so it doesn’t capture the commanding heights (ergo, why I’m quoting Modi).

Addendum: One issue for me is that I have a hard time taking Indian pseudoscience seriously just as I have a hard time taking Creation Science seriously. Sincere, earnest, and sometimes bright, people taking absurd claims seriously and constructing models out of them strikes me as farcical and funny more than threatening.

December 19, 2018

The Insight Show Notes — Season 2, Episode 10: 2018 in genomics

Filed under: Genomics,science — Razib Khan @ 10:34 pm

The Insight Show Notes — Season 2, Episode 10: 2018 in genomics

This week we reviewed the “big stories” in 2018 in genomics. There were a lot of possibilities, but we narrowed down the list.

First, we discussed Neanderthal art. And, it’s ramifications for the “Great Leap Forward” in behavioral modernity.

The second story involves the post-Roman barbarian migrations. With the relative cheapness of ancient DNA techniques, researchers are expanding the purview of their topics to more recent periods, in particular domains where written and archaeological evidence are not clear.

Next, we talked about the sequencing of an F1 of a Denisovan male and a Neanderthal female. That is, this individual had a mother from one group of humans, Neanderthals, and a father, from another, a Denisovan. The probability of discovering such an individual seems low, and they researchers stumbled upon this! No one like this is present today. But was it different in the past?

The fourth story was the discovery of the Golden State Killer through DNA pedigree analysis. Serial killers beware!

Then we discussed the polygenic risk score of educational attainment. With more than 1 million samples, 2018 saw the next step in the intersection of genetics and traits.

Citation: Khan, Razib, and David Mittelman. “Consumer genomics will change your life, whether you get tested or not.” Genome biology 19.1 (2018): 120.

2018 was the year that the consumer genomics went mainstream, with more than 20 million customers. The sector has finally broken out of nerd culture into pop culture.

It was also the year that DNA came to politics, as Elizabeth Warren released genetic results that indicated some amount of Native American ancestry.

Finally, the year in DNA ended with the “CRISPR babies” story.

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 10: 2018 in genomics was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

December 12, 2018

The Insight Show Notes — Season 2, Episode 9: the genetics of Africa

Filed under: Africa,paleontology,science — Razib Khan @ 3:46 pm

The Insight Show Notes — Season 2, Episode 9: the genetics of Africa

This week on The Insight (Apple Podcasts, Stitcher and Google Podcasts) Razib Khan and Spencer Wells discuss the genetics of Africa, and how our human story has become more complicated over the past few years.

Modern population mtDNA phylogeny (M & N are found outside Africa)

First, we talked about “mtDNA Eve,” which helped inspire the correct idea that all modern humans descend overwhelmingly from a group of Africans that lived in the relatively recently in the past (in geological time!). These results were also confirmed by “Y chromosomal Adam.” Both the common maternal and paternal ancestor through uniparental lineages lived in Africa within the last few hundred thousand years ago in the past.

We also alluded to the ideas of Richard Klein, who in the early 21st century crystallized the model whereby modern-day humans descend exclusively from a small East African population which flourished about ~60,000 years ago.

We talked about the results of archaic introgression into modern humans. Particularly the admixture of Neanderthals into non-Africans. This put a chink in the armor of the total replacement model which had become popular around the turn of the century. Additionally, Nordborg’s 1998 paper, On the probability of Neanderthal ancestry illustrated the limitations of using a single locus long ago.

Our conversation with Milford Wolpoff for The Insight podcast was alluded to. We discuss the reemergence of “multi-regional” frameworks in the context of the evolution of modern humans within Africa.

The paper, Did Our Species Evolve in Subdivided Populations across Africa, and Why Does It Matter? outlines the current state of flux.

We mention both early work on archaic admixture in Africa, not accepted at the time, and newer work which seems to confirm the general result.

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

Most of human history was in Africa

Filed under: Africa,Genetics,Human Evolution,science — Razib Khan @ 12:31 am
Citation: Scerri, Eleanor ML, et al. “Did our species evolve in subdivided populations across Africa, and why does it matter?.” Trends in ecology & evolution (2018).

Over the last generation our understanding of the origin of what we term “modern humans” has undergone two revolutions. Or, perhaps more precisely, a revolution was won, and an evolution overturning much of the revolutionary orthodoxy is now occurring.

Starting with the emergence of “mitochondrial Eve” in the 1980s, and moving to with genome-wide analysis in subsequent decades, a certain narrative emerged that modern humans, Homo sapiens, evolved in a small region of East Africa ~60,000 years ago, and spread rapidly across the whole world. In the process, they replaced “archaic human” populations, the most famous of which were the Neanderthals. It was a “human revolution,” with some paleoanthropologists giving credit to our species’ special genius, perhaps even the invention of language.

Neanderthal

Though there were those who disagreed, the dominant view that Neanderthals and our other human cousins were genetic dead-ends was so strong that it suffused many different fields. This changed in 2010, as the Neanderthal genome revealed that people outside of Africa seem to have had Neanderthal ancestry. A different genome from another human population called Denisovans, yielded the finding that Oceanians, and to a far lesser extent East and South Asians, have ancestry from this group of ancient humans.

The total replacement idea has now fallen by the wayside. But what about the idea that the dominant component of modern human ancestry expanded from East Africa 60,000 years ago? For several decades the Omo Kibish fossil from Ethiopia highlighted that the origins of modern humans were likely far older. Dated to 195,000 years ago, this individual was anatomically modern. The skull looks like that of contemporary peoples.

Omo reconstruction

A different argument was that “behavioral modernity” arose 40,000 years ago. Even if the physical characteristics we associated with modern humans were present earlier. The problem with this line of thought is that it seems that Neanderthals and Africans were engaging behavior we would define as “behaviorally modern” before 40,000 years ago. It could simply be that behavioral modernity was a quantitative change in the rate of cultural evolution.

Not only that, but a very early “proto-modern” human skull has now been found in Northwest Africa, in Morocco. One of the lynchpins for the East African origin of modern humanity was the antiquity of Omo Kibish, but the Jebel Irhoud remain dates to over 300,000 years ago! With a melange of modern and non-modern features, though this individual cannot be defined as strictly anatomically modern, it seems that a population proceeding in that direction flourished during this time in the north of the African continent.

San tribesman

The data from genetics has complicated our understanding of the origins of modern humans within Africa as well. Groups such as the San of southern Africa do not seem to have the same evidence of a rapid population expansion from a tight bottleneck as non-African populations. And even within Africa, the San maintained a relatively large population size over tens of thousands of years. The latest work suggests that they diverged from other modern populations at least 200,000 years ago.

All this points to the fact that though the story of modern human expansion from the edge of the Middle East ~60,000 years ago, into all of Eurasia, and then Oceania and finally New World, is one of explosive growth from a small founder group, and then some assimilation of Neanderthals and Denisovans. The emergence of modern humans in Africa is more complex. The story is not neat and tidy, and currently unfinished. Using genome analysis from a wide array of populations, modern geneticists are now uncovering evidence of “deep structure” within Africa.

Instead of a relatively recent explosion of humanity, the emergence of the modern lineage that we see around us today for most of its history seems to have been a more gradual affair, defined by the interconnection of populations with multiple geographical nodes. It may not “even be wrong” to assert that there was a particular region from which the dominant modern human lineage arose within Africa. If one takes the divergence of the Bushmen 200,000 years ago as a floor for the emergence and diversification of our lineage, then 70% of the time down to the present consisted of a purely African set of populations.

And, as modern humans spread out across Africa, it seems that just as in Eurasia, our ancestors interacted with cousin lineages of humans. Without ancient DNA there will be no smoking gun, but the circumstantial evidence is highly suggestive, and points in the direction of local admixture within the continent. The expansion out of Africa then may simply have recapitulated ancient patterns within our species.

Maybe you have some Neanderthal or Denisovan in your DNA. Discover your story today with Neanderthal by Insitome.


Most of human history was in Africa was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

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.

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