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April 24, 2019

The Insight Show Notes — Season 2, Episode 24: Deconstructing the Denisovans

Filed under: Denisovans,Podcast,science,Uncategorized — Razib Khan @ 2:55 pm

The Insight Show Notes — Season 2, Episode 24: Deconstructing the Denisovans

The Dali skull, 200,000 years old. A Denisovan?

This week on The Insight (Apple Podcasts, Spotify, Stitcher and Google Podcasts) Spencer is back, as we go back to our old two-man show format (at least for this episode). We discuss “deconstruct” the Denisovans, one of the newest human species discovered by science.

The Altai

But before we dug into the paleogenomics, Spencer discussed the human and physical geography of Inner Asia, and in particular the Altai region. In the 1990s Spencer had the opportunity to sample the native peoples of the region, which eventually turned in the Eurasian Heartland paper.

We put the critical role of Inner Asia in a broader historical perspective, from the early Indo-Europeans, down to the Mongols and Turks, and finally the “Great Game” of geopolitical rivalry between Britain and the Russian Empire in the 19th century.

The Altai in many ways has been at the center of Inner Asia. Spencer reflects on the fact that this is where there are Shambhala is often located, a mythical utopian kingdom. While the region is surrounded by cold deserts and forbidding mountains, with the Siberian vastness to the north, the Altai region harbors some relatively sheltered valleys through which nourishing rivers flow.

Inside the Denisova cave

Denisova cave also happens to be in the Altai. This means that not only has the Altai been of historical and mythic importance, but it has been at the center of the understanding of human evolution, and perhaps at the center of human evolution!

We discuss the multiple Denisovan individuals which have been sequenced from the cave. And, the first human ‘hybrid’, a woman whose father was Denisovan, and whose mother was Neanderthal, ‘Denny.’ Denisova cave was inhabited both by Neanderthals and Denisovans, with the Neanderthals having some evidence of modern human admixture, and the Denisovans Neanderthal admixture (and perhaps late Homo erectus).

But the Denisovans were not just a Siberian species. New work suggests there were three deeply distinct Denisovan populations, at least. The people of New Guinea may have had at least three mixing events with Denisovan people, while the admixture in China is almost certainly from a different Denisovan population than that in Oceania.

Finally, we talk about Homo luzonensis, and what the diversity of human across eastern Eurasia means in relation to what it “means to be human.”

The Insight Show Notes — Season 2, Episode 24: Deconstructing the Denisovans was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

April 23, 2019

Denisovans and the human story

Filed under: Denisovans,Human Evolution,Neanderthals,science — Razib Khan @ 1:38 pm
The Siberian cave where a new human species was discovered

We are all aware of the iconic fossil finds which mark the various milestones of our understanding of human evolution. The story of how our species became what it is today. Raymond Dart’s Taung Child helped establish that Africa might be the original home of our species. Lucy, which put the spotlight on some of the earliest upright ancestors of hominins. Even frauds like Piltdown Man go down in the history books, at least reflecting something of a particular Zeitgeist, wrong as it was.

And yet our past is haunted by a very small collection of remains indeed. Humans were never numerous (until recently). Our ancestors were fossilized thanks to luck, giving us a sense of the shape their form and bearing. The fossil trail of the upright line of apes which eventually lost their fur, and left Africa two million years ago, is quite tenuous.

Denisovan teeth from which DNA was extracted

But in the 21st-century new varieties of humans, species perhaps, are not discovered just by fossils alone. Rather, genetic science has now become adept at retrieving DNA from even the most ancient of human remains. Geneticists can then reconstruct the history of peoples long gone from their sequence, and compare them to modern people or other ancient genomes.

In the spring of 2010, the first whole Neanderthal genome was published, a landmark in the development of paleogenetics. Of course, Neanderthals have a long and storied history in paleoanthropology. They’ve been dehumanized and rehumanized and dehumanized many times. The surprise results out of the Neanderthal genome was that humans outside of Africa were all related to the Neanderthals. In other words, a few percent of the genome of non-Africans could be attributed to descent from them.

But wait! 2010 had more surprises in store for us. At the end of the year, a paper reported the genome of a new species of human. Previously unknown to science, these were the Denisovans, named after the cave in Siberia in which the remains were found. Because there was a genome of Neanderthals already sequenced, scientists could tell that the Denisovans were closer to Neanderthals than to modern humans. About ~750,000 years ago the ancestors of Neanderthals and Denisovans left Africa, separating from our own ancestors. Soon after, the Neanderthals and Denisovans began to diverge, becoming two distinct lineages, far more distinct than any two modern groups.

But why were they distinct?

To answer the question one must look at a map. While Neanderthals occupied Europe and ranged east into the heart of Eurasia, Denisovans likely inhabited the zone between eastern Siberia down into Southeast Asia. Differences develop between populations with common ancestors when they are geographically separated, and by and large (though not exclusively), Denisovans and Neanderthals were separated by the vast arid heart of Eurasia.

While the Neanderthals were a northern population, despite the discovery of Denisovans in a Siberian cave, they may have been used to warmer climes more often than not.

Papuan Woman and Child

One reason this seems likely is that Denisovans have descendants today. But they are not an obscure group in Siberia…they are the Papuans of New Guinea! This population has about ~5 percent of its genome from Denisovans. The descendants of these ancient people are also more widely scattered across Oceania, though to varying degrees.

While the Australian Aboriginals and Negritos of the Philippines have significant Denisovan ancestry, the native tribes of the Andaman Islands have little. This suggests that not all indigenous peoples of South and South Asia mixed equally with Denisovans.

More recent work has revealed that much lower levels of Denisovan ancestry are present across much of South and East Asia. And, importantly, the Denisovan ancestry in groups like the Chinese seems to be from a different group than that mixed into the Papuans. The genome from Denisova cave likely belongs to the people who mixed with East Asians and contributed adaptative functions such as high altitude adaptation in Tibetans.

So what we know now is that for hundreds of thousands of years a widespread group of humans, Denisovans, occupied eastern Eurasia. Unlike Neanderthals, they were not a single homogeneous group. Some research groups have detected three different Denisovan populations mixing into modern humans, while others have suggested that the Denisovans carry ancestry from even earlier hominins, who likely arrived in Asia before them.

But unlike Neanderthals or our African forebears, we have not been able to reconstruct a full skeleton of an individual who is Denisovan.

There are skullcaps, teeth, and stray bones, but not enough identified remains which could give us a sense of what these people looked like, how they were built (though the fragments from Denisova cave indicate to many the Siberian population was robust). Despite what we know was their expansive range, and the fact that they lived in eastern Eurasia for hundreds of thousands of years, to a great extent Denisovans remain genetic ghosts. They are digital shadows of their physical bodies, telling us about their relationships to other humans, details of their physiology, and immune system, but elusive in corporeal form.

The discovery of a new human on the island of Luzon, the existence of hobbits on Flores, and the diversity of Denisovans suggest that the eastern range of humanity during the Pleistocene was filled with many species of humans. The very existence of the Denisovans was window upon the vast ignorance of science in regards to the complexity of the Pleistocene world.

While Neanderthals have been the subjects of many books, they may have been a relatively homogeneous population with very precise adaptations to their northern Eurasian abode. A literal evolutionary sideshow. In contrast, Denisovans ranged from Siberia to the islands of Southeast Asia. From the edge of the tundra to the hot savanna of Sundaland.

They reflect in greater fullness the range of human experience.

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

April 3, 2019

The Insight Show Notes — Season 2, Episode 21: The Genetic History of Ice Age Europe

Filed under: science — Razib Khan @ 2:50 pm

The Insight Show Notes — Season 2, Episode 21: The Genetic History of Ice Age Europe

Aurignacian artifacts

This week on The Insight (Apple Podcasts, Spotify, Stitcher and Google Podcasts) we discuss the genetic history of Ice Age Europe with Cosimo Posth, a postdoctoral scholar at the Max Planck Institute for Human History.

Cave of Altamira

Much of the discussion revolved around various success modern human cultures of the Ice Age in Europe. Aurignacian, Gravettian, Solutrean, Magdalenian, and Epipaleolithic cultures were mentioned. We also discussed the idea of Ice Age refugia.

There was extensive discussion of the idea that there were multiple population turnovers. And, several papers relating to ancient DNA were mentioned.

The Insight Show Notes — Season 2, Episode 21: The Genetic History of Ice Age Europe was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

March 26, 2019

The arrow of evolution

Filed under: History,philosophy,science,Teleology — Razib Khan @ 11:46 pm
5,000 years of change

Most evolutionary biologists would agree with the contention that evolution has no long-term direction. In other words, evolutionary change is shaped by the contingencies and exigencies of the present set of circumstances, searching blindly through “adaptive space” for local optimal solutions. Just “good-enough.” For now.

In the realm of biology, this is illustrated by various “retrofits” one can see in form and function. The human vertebrate is a notoriously suboptimal feature, but it is the outcome of hundreds of millions of years of prior evolution when our ancestors were primarily quadrupeds. We make upright posture and bipedal locomotion work for us, but there’s a reason that prehistoric bipedal dinosaurs would likely run us down with ease. Jurassic Park isn’t all fantasy.

Upright hominins are utilizing new engineering technology which still has a lot of “bugs.”


Even the classic view of human evolution where short slouching creatures become upright moderns requires a rethinking. The reality is that Homo erectus was probably already as tall, on average, as modern human populations. And until contemporary times the tallest human populations known seem to date from the Pleistocene. Humans have been shrinking since their Paleolithic peak, with the 20th-century spike across the developed world reversing millennia of decline.

If evolution has a goal, oftentimes it looks like it hasn’t made up its mind.

The late paleontologist Stephen Jay Gould made a forceful case for the importance of chance and necessity, randomness, in the diversity of life on earth. In his book A Wonderful Life, he states:

The divine tape recorder holds a million scenarios, each perfectly sensible. Little quirks at the outset, occurring for no particular reason, unleash cascades of consequences that make a particular feature seem inevitable in retrospect. But the slightest early nudge contacts a different groove, and history veers into another plausible channel, diverging continually from its original pathway. The end results are so different, the initial perturbation so apparently trivial.

Gould’s understanding of evolution is at one extreme of the views about the role of randomness, and lack of purposiveness, of natural history. It should not be a surprise that his view is not universally held.

The researcher upon whose work his argument in A Wonderful Life was built, Simon Conway Morris, strongly disagreed with Gould’s interpretation of paleontology and natural history. In a series of books, he outlined the idea that evolution does have a broad directionality due to various forces, such as the necessity of streamlined body-plans for predators in the ocean. The fact that dolphins resemble ancient Mesozoic marine reptiles is obviously not a coincidence and illustrates that rewinding the tape only led to large-bodied land vertebrates converging upon the same body plan to adapt to the oceans.

Ichthyosaur from the Mesozoic

Richard Dawkins reiterates this argument in The Ancestor’s Tale. Dawkins also observes that over the billions of years that life has been present on earth, there seems to be a gradual, if sometimes halting, progression toward greater complexity. Most of our planet’s history was dominated by cyanobacteria and other prokaryotes, but more recently multicellular life forms have emerged to make up a much greater proportion of the biomass and dominate ecosystems. Despite mass extinctions such as the one at the end of the Permian or the event that resulted in the extinction of dinosaurs 60 million years ago, multicellular life is here to stay.

Now, over the last several million years humans have been expanding across the face of the earth and reshaping the landscape. While it is easy to dismiss humans as just another medium-sized megafauna, today we and our domesticates account for 96 percent of the mammalian biomass on planet earth!

Human occupation and seen through the lights we produce

This is amazing in light of the fact that tens of thousands of years ago it seems likely that our species numbered in the tens of thousands. Today we number in the billions. It is just our luck and happenstance?

Humans are wont to perceive themselves as the pinnacle for creation, so scientists are cautious and skeptical of presuming we are in fact something special. Much of modern science has been involved in the project of showing just how banal our place in the universe is. An extension of the Copernican project, which rejected the old idea that the earth was the center of the universe.

We’re on the edge of a spiral galaxy, on a small planet circling a modest G-class star. Our species has been present on this planet for a tiny fraction of its existence of 4 billion years. What are we in the grand scheme of things?

And yet, it is quite likely that we are the first intelligent species on this planet capable of exploiting its mineral resources, judging by the fact that there were so many exploitable surface deposits of coal and iron during our own industrialization. The emergence of humans was also likely a final push in the extinction of numerous megafauna at the end of the Pleistocene, which had persisted through many interglacials.

Humans were the first large placental mammal to arrive in Australia and New Zealand, eventually bringing a host of others in their wake. No other large mammal seems to have been able to occupy six of the seven continents before our own species. And this feat was achieved 15,000 years ago when we were small hunter-gatherer bands.

Today, the entire biogeography of the planet has been resculpted by us, from red deer in New Zealand to European earthworms in North America.

This is then the “Anthropocene.” An age when humanity holds the leash on the planet’s biosphere and engages in endeavors which will change the future of the planet, or endanger it….

Breaking the Malthusian trap!

The pessimistic outcomes for the planet due to the evolution of humans, an intelligent, social, and technological, species have been well aired. But what about the optimistic ones?

There are some thinkers who have long argued that evolution on this planet was almost certainly at some point going to produce intelligent technological life. The “encephalization” of large animals on this planet, the relative size of the brain in relation to the body, had been gradually increasing long before the emergence of the hominin lineage, which is well known to be defined by very large brains.

If organisms are biological machines, the machines have been getting more complicated over time.

In the 1950s a Catholic priest and paleontologist named Pierre Teilhard de Chardin promoted the idea that evolution was driving the universe toward a cosmic consciousness. Most scientists were very skeptical of such teleological thinking. That evolution had some ultimate purpose beyond optimizing local fitness. Some direction toward a final culmination. Today, they still remain very skeptical.

Decades later in the 1990s the science writer Robert Wright wrote Nonzero: The Logic of Human Destiny. In it, he argued that evolutionary processes were leading up to humans and that our species was advancing through “non-zero sum” interactions. We had broken the grip of Malthus and the standard carrying capacity charts of ecologists through cultural innovation.

Today, David Sloan Wilson, a mainstream evolutionary biologist, argues that selection pressures on human groups may have driven increases in altruism and prosocial behavior to such an extent that he now imagines that successful completion of the Darwinian project may lead exactly to some sort of global consciousness, as envisaged by de Chardin. A mind which is able to optimize fitness at the level of the whole planet.

Of course, even David Sloan Wilson is not speaking in terms of inevitabilities. The Anthropocene is a dangerous time for the long-term time horizon of the planet’s ecosystems. The evolution of modern humans and their cultural creativity has unleashed a Pandora’s box of problems. But Wilson and his fellow-travelers seem to be suggesting that this is not just chance and necessity. That the earth has two possible final outcomes, one dire, and one nearly utopian.

And remember, opening Pandora’s box also unleashed “hope” upon the world.

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

March 6, 2019

The Insight Show Notes — Season 2, Episode 17: Polygenic risk scores and diversity

Filed under: Genetics,Medicine,Podcast,science — Razib Khan @ 4:55 pm

The Insight Show Notes — Season 2, Episode 17: Polygenic risk scores and diversity

The risk for coronary heart disease

This week on The Insight (Apple Podcasts, Stitcher and Google Podcasts) we discuss “polygenic risk scores” (PRS) and genetic diversity with Dr. Alicia Martin. She is a researcher in the Analytical and Translational Genetics Unit at the Broad Institute of MIT and Harvard in Cambridge, MA.

Citation: Martin, Alicia R., et al. bioRxiv(2019): 441261.

We talked first about the general idea of “polygenic risk scores.” Based on centuries-old techniques of statistical prediction of an outcome (a “risk”) from numerous variables (which include various genes), the age of genomics has allowed for there to be enough data that individual genomes could be analyzed to produce results of utility. But as noted in recent work, the prediction varies by population. The accuracy is far higher in Europeans than in non-European populations, strongly correlated with phylogenetic distance.

One of the major reasons for this difference is the evolutionary history of our species. The “out of Africa” migration meant that Africans and non-Africans split first. Then Europeans from Asians.

When researchers do studies on Europeans, they “discover” variation in that population, and miss out on variation that is unique to other groups. This reduces the power of the predictions as a function of evolutionary divergence.

We discuss the various reasons for the low diversity in modern medical genomics. One reason is that European nations have taken the lead in consortiums. This means that they have a headstart and since genetic studies are easier in large numbers of homogeneous groups due to “stratification,” researchers kept studying the same populations over and over again.

This leads to accumulating differences in how well the technology is suited to different populations. For example, patterns in the genome known as “linkage disequilibrium,” the association of alleles across genes, is far more well known for Europeans. And these patterns are essential in maximizing the power of a given PRS.

We discussed Martin’s paper from 2017, Human Demographic History Impacts Genetic Risk Prediction across Diverse Populations, which pioneered the systematic exploration of this topic. And, we talked about the path forward, and how we can solve this problem.

The Insight Show Notes — Season 2, Episode 17: Polygenic risk scores and diversity was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

February 19, 2019

Arabia between Africa & Eurasia

Filed under: Evolution,Genetics,Human Evolution,science — Razib Khan @ 1:57 am

Arabia between Africa and Eurasia

Shanidar cave in Iraq, once occupied by Neanderthals

For hundreds of thousands of years Neanderthals and the ancestors of modern humans interacted in the broad zone of territory we now call the “Middle East.” Neanderthals occupied sites across the Fertile Crescent, while Arabia and parts further north were settled on and off by people related to and possibly ancestral to modern humans. Before the expansion of our ancestors across Eurasia, and into Oceania, 50,000 years ago, a situation of dynamic equilibrium persisted as the Near East existed as an ecozone in flux between that of northern Eurasia and northern Africa. Between Neanderthal and modern human.

Though there is no doubt that Africa is the great reservoir for the vast majority of human ancestry today, by dint of their locations Arabia and the Fertile Crescent are essential pieces of the broader jigsaw puzzle of the human story. Modern humans either migrated north through the Sinai from Africa. Or, they crossed the straits that divide modern Yemen from Africa on the southern edge of the Red Sea. Of course, they could have done both!

But as modern humans were pushing north and east, this region was long occupied by Neanderthals. Today we know that all non-Africans carry Neanderthal ancestry. One of the simplest explanations for this is that the admixture occurred in the Middle East, as modern humans came into contact with their cousins. As they migrated onward, north and east, they did not mix so much with the Eurasian hominins that lived in those regions.

The problem with this theory is that different methods of analysis have shown that Neanderthal ancestry varies across many populations, even when you remove African ancestry from the equation. In short, many assessments conclude that East Asians have more Neanderthal ancestry than Europeans, who have more Neanderthal ancestry than people in the Middle East.

Why could this be? One of the most popular explanations is that East Asians have had more mixture with Neanderthal-like populations. That is, there was a later mixture event. Meanwhile, people in the Fertile Crescent and Arabia mixed with people who were not African but split from other “Out of Africa” populations before the admixture with Neanderthals. These people are awkwardly called “Basal Eurasians,” meaning they split off before the other groups diversified into all the lineages from Europe to Australia.

But new research suggests another possibility: all Africans may have ancestry from “West Eurasian” populations which moved back into Africa after the “Out of Africa” event ~50,000 years ago. For statistical reasons beyond the purview of this post, this affinity between West Eurasians and Africans may lead to incorrect estimates of Neanderthal ancestry varying across Eurasian groups, when in fact it is simply affinity to Africans which varies across groups. West Eurasians and Africans are simply genetically more similar than East Eurasians and Africans.

More work needs to be done about who these West Eurasians were. But, keep in mind that Arabians and Levantines do show less Neanderthal ancestry in the older framework than even Europeans, implying that the “West Eurasians” were likely from the Near East, which is the most reasonable scenario geographically in any case for a “back migration” to Africa.

Though it is certainly true that “we are all Africans” under the skin, least within the last 50,000 years, in some sense all Africans may be a bit Arabian….

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

Arabia between Africa & Eurasia was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

February 17, 2019

Pakistan’s #1 in newborn mortality rates!?!?!

Filed under: Mortality,science — Razib Khan @ 12:59 am

Sometimes you read things you need to double check on. World is failing newborn babies:

1. Pakistan: 1 in 22
2. Central African Republic: 1 in 24
3. Afghanistan: 1 in 25
4. Somalia: 1 in 26
5. Lesotho: 1 in 26
6. Guinea-Bissau: 1 in 26
7. South Sudan: 1 in 26
8. Côte d’Ivoire: 1 in 27
9. Mali: 1 in 28
10. Chad: 1 in 28

Let’s let that sink in. Pakistan has worst mortality rate for newborns than Afghanistan, South Sudan, and the Central African Republic. Nations riven by conflict, warfare, and general underdevelopment.

I wouldn’t mind if someone pointed out how there is an artifactual bias in the above analysis. The numbers are horrifying, especially in light of the fact that Pakistan is more prosperous than most of those countries.

You shall judge a nation by how it treats the least amongst us.

February 16, 2019

Why do South Asians have heart disease?

Filed under: Health,science — Razib Khan @ 9:13 pm

Why Do South Asians Have Such High Rates of Heart Disease?:

Some of the most striking findings to come out of Masala relate to body composition. Using CT scans, Dr. Kanaya and her colleagues found that South Asians have a greater tendency to store body fat in places where it shouldn’t be, like the liver, abdomen and muscles. Fat that accumulates in these areas, known as visceral or ectopic fat, causes greater metabolic damage than fat that is stored just underneath the skin, known as subcutaneous fat.

…. Cardiovascular risks tended to be highest in two groups: those who maintained very strong ties to traditional South Asian religious, cultural and dietary customs, and those who vigorously — embraced a Western lifestyle. Those with lower risk are what the researchers call bicultural, maintaining some aspects of traditional South Asian culture while also adopting some healthy Western habits.

This discrepancy plays out in their dietary behaviors. Almost 40 percent of Masala participants are vegetarian, a common practice in India that is widely regarded in the West as heart healthy. But vegetarians who eat traditional South Asian foods like fried snacks, sweetened beverages and high-fat dairy products were found to have worse cardiovascular health than those who eat what the researchers call a “prudent” diet with more fruits, vegetables, nuts, beans and whole grains (and, for nonvegetarians, fish and chicken). People who eat a Western style diet with red and processed meat, alcohol, refined carbohydrates and few fruits and vegetables were also found to have more metabolic risk factors.

I think one of the issues with the “traditional” lifestyle in combined with modern affluence is that they aren’t actually eating like their (our) ancestors would eat. Though friend snacks and sweetened beverages are acceptable in vegetarian diets, I doubt that this was on the menu for many Indians who lived on vegetarian diets.

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.


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.


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.

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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.

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