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June 20, 2019

Of proteins and paleontology

Filed under: Evolution,Genetics,protein,science — Razib Khan @ 9:04 am
Ostrich egg

Ancient DNA has transformed our understanding of the biological past. The sequencing of mammoths, moa, and Neanderthal have opened up a window upon evolution which we had previously only perceived through material remains. Whereas 20 years ago there was only one human genome, today there is an excellent whole genome of a species of human we had not even known existed a generation ago.

Genetic information from the past is so useful because it fills in the gaps of the tree of life. With modern species, scientists have to “infer” the relationships based on assumptions within particular phylogenetic models. Ancient DNA allows them to fill in deeper “nodes” within this tree with a high degree of confidence.

While a skeleton has a great deal of information and allows scientists to make evolutionary inferences, DNA consists of discrete bits which reflect the whole past genealogy of an organism many generations ago.

But there is a downside to DNA: it degrades. Where fossils can be preserved for billions of years, the oldest DNA sequence dates to ~700,000 years ago. There are vast quantities of ancient DNA today in databases, but a very high proportion dates to the last 10,000 years, and an overwhelming number to higher latitude samples.

The decreasing concentration of ancient DNA

In fact, the ~1,000,000 years may be an upper bound for how far back ancient DNA is viable for sequencing analysis. The concentration beyond this point of DNA from the sample itself is just too low to extract it out of bacterial contamination. This does not even consider the reality that in tropical and moist climates the conditions are far less amenable to long-term preservation.

But are fossils the only alternative then for paleontologists? It turns out not. DNA is not the only molecule from ancient remains that is useful for scientists. There are proteins!

Proteins are the product of processes which start with DNA:

DNA is transcribed to RNA which is translated to protein

And, they are far more robust than DNA. Proteins have been extracted from ostrich eggshells in Tanzania dated to 3.8 million years ago. Note that not only does this smash the 1 million year barrier, but it is also from a hot climate where DNA degradation is such that very ancient dates are unlikely in the first place.

That being said, there are limitations to protein analysis. Only about ~1% of the human genome, the exome, is translated into protein. And that proportion of the genome is often less diverse than the other proportions. This is due to the fact that mutations in functional regions of the genome are often strong selected against, as they are more likely to “break” something.

As genetic variation is the raw material for phylogenetic analysis, this means protein sequence will be less informative than DNA sequence.

The second major issue is that protein extracted from bone, dentine, and enamel, to name a few tissues preserved in mammals, is not representative of all the proteins in the body. While DNA is the whole sequence, only a subset of DNA is expressed in particular tissues at particular times. This means that the proteins will differ across the body, and some proteins are going to vary a great deal less than others due to their importance in many species. Collagen is the most abundant protein, so it is not surprising then that the analysis of protein sequence will focus on the collagens.

Because protein offers less information, it will be less useful for generating subtle population genetic statistics than DNA. Rather, ancient protein analysis will shine in taxonomic identification of remains.

In the context of humans, this is relevant, because the hominin lineage dates to considerably earlier than 1 million years ago. The famous discovery, Lucy, dates to 3.2 million years ago.

Over the next few years, ancient protein analysis will become more refined and powerful. It is quite possible that that the “family tree” of our species before 1 million years ago will be rearranged by geneticists again, just as our more recent ancestry and relationship to Neanderthals has been revolutionized. Ancient proteins may aid in resolving who our “first ancestors” actually were….

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

June 19, 2019

The Insight Show Notes — Season 2, Episode 32: Tibetan Denisovans!

Filed under: Denisovans,Genetics,paleontology,science — Razib Khan @ 2:50 pm

The Insight Show Notes — Season 2, Episode 32: Tibetan Denisovans!

Denisovan Mandible

This week on The Insight (Apple Podcasts, Spotify, Stitcher, and Google Podcasts) Razib talks to Dr. Frido Welker, a pioneer in the field of ancient protein phylogenetic analysis of human remains. We talked about the recent finding of Denisovans from the highlands of Tibet, work on which he was a researcher.

The paper, A late Middle Pleistocene Denisovan mandible from the Tibetan Plateau, uses protein analysis to find that an ancient sample from Tibet clusters with the Denisova genome. This is important because this is the first confirmed publication which reports on a Denisovan outside of the Altai cave site in Siberia. The authors did not find DNA, so they had to make recourse to protein, which is more robust than DNA.

Using a few positions they inferred that the Xiahe sample was closest to the Denisova cave sample.

Because they had a mandible, the authors confirmed again the robustness of the Denisovans (the teeth of the Denisova cave sample were inordinately large, but that was a single sample). Along with a skull cap reported at a conference in March, this brings confirmed Denisovans to three individuals across Northeast Asia. This, despite the fact that in terms of genomics the most “Denisovan” modern populations are those far to the southeast, in Oceania.

We also discussed how protein analysis will complement ancient DNA analysis. Though proteins have less informative variation than DNA, they are likely to last much, much, longer. The oldest agreed ancient proteins being from nearly 4 million years ago!

The Insight Show Notes — Season 2, Episode 32: Tibetan Denisovans! was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

May 22, 2019

The Insight Show Notes — Season 2, Episode 28: Altitude Adaptation and Denisovans

Filed under: Adaptation,Genetics,science,Tibet — Razib Khan @ 2:57 pm

The Insight Show Notes — Season 2, Episode 28: Altitude Adaptation and Denisovans


This week on The Insight (Apple Podcasts, Spotify, Stitcher and Google Podcasts) Razib talks to Emilia Huerta-Sanchez, a computational biologist at Brown University about one of the most fascinating findings that came out of evolutionary genetics in the last ten years.

The story began around 2013 when a research group in Berkeley published results that suggested strong signatures of adaptation in EPAS1 for Tibetans. The curious aspect here is that on the whole the genetic variation of Tibetans and Han Chinese, two closely related populations, was strongly correlated. But on EPAS1 something different occurred.

Emilia was doing a follow-up project when she realized that she couldn’t find other modern populations which seems to have been a source for this new mutation, which rose in frequency in Tibetans relatively recently. Surveying the ancient DNA data she found the striking result the genetic region of Tibetans in EPAS1 matched the same section of the Denisovan genome!

This resulted in the paper, Altitude adaptation in Tibetans caused by introgression of Denisovan-like DNA.

Eventually, this paper, which started as a side-project, led to an interest in altitude adaptation and archaic populations. For example, the paper Genetic signatures reveal high-altitude adaptation in a set of Ethiopian populations and Evidence for archaic adaptive introgression in humans.

Much of the discussion focused on the role of serendipity in science, as the researchers kept having to change their understanding of the model until they realized what they were getting wrong.

We talked extensively Denisovans again, and Browning and Browning came up again, Analysis of Human Sequence Data Reveals Two Pulses of Archaic Denisovan Admixture.

The Insight Show Notes — Season 2, Episode 28: Altitude Adaptation and Denisovans was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

May 15, 2019

The Insight Show Notes — Season 2, Episode 27: Neolithic Massacre

Filed under: Archaeology,History,science — Razib Khan @ 2:56 pm

The Insight Show Notes — Season 2, Episode 27: Neolithic Massacre

This week on The Insight (Apple Podcasts, Spotify, Stitcher and Google Podcasts) Razib talks to an archaeologist and geneticist who were authors of a paper that documented a Neolithic massacre of a group of people in Poland ~4,500 years ago.


The work here is very interdisciplinary. A generation ago this would be mostly placed in the archaeological context of the culture that these individuals came from, Globular Amphora people. These are the last of the Neolithic farming societies of Northern Europe. That is the societies that derive from the expansion of agriculturalists from the southeast, originally from Anatolia (whose closest modern relatives are Sardinian).

These were replaced and assimilated about ~4,500 years ago by the steppe people, the Corded Ware culture. This site in southern Poland was situated on the border between Globular Amphora and steppe societies during a time of transitions.

The most novel aspect of this publication is that they’ve obtained whole-genome sequences, which allowed them to reconstruct patterns of kinships. Conventional archaeology of this sort focuses on age and sex, as well as the position of people buried. This paper overlaid upon that information about kinship relationships.

It was like taking a two-dimensional picture, and adding the depth of human relationships atop that, and so bringing it into a whole new area of narrative inference. Likely this is the future for these sorts of reconstructions. Prehistory will remain before history, but the genealogies of the past will come to life.

The Insight Show Notes — Season 2, Episode 27: Neolithic Massacre was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

May 8, 2019

The Insight Show Notes — Season 2, Episode 26: The Epigenetics Revolution

Filed under: Epigenetics,Podcast,science,The Insight — Razib Khan @ 3:00 pm

The Insight Show Notes — Season 2, Episode 26: The Epigenetics Revolution

This week on The Insight (Apple Podcasts, Spotify, Stitcher and Google Podcasts) Razib talks about the “Epigenetics Revolution” with John Greally of Albert Einstein School of Medicine. A pediatrician who is interested in diseases with an epigenetic dimension, John also happens to be writing a textbook on the topic!

Conrad Waddington

The term epigenetics goes back to Conrad Waddington’s work in the 1940s. He was interested in developmental biology. At the time this involved descriptions of and mapping out changes over time in the structure of organisms at various scales. Waddington suggested that epigenetics “the task is to discover the causal mechanisms at work…revealed of the mechanics of development.” Developmental biologists of the time were showing the trajectory of change, but not the underlying mechanisms.

In other words, epigenetics in Waddington’s conception was an elucidation of the mapping from genotype to phenotype.

By the end of the 20th-century biologists were living in the DNA era. Ryan Holliday proposed in 1990 that particular molecular mechanisms should be given preeminence:

Epigenetics comprises the study of the mechanisms that impart temporal and spatial control on the activities of all those genes required for the development of a complex organism from the zygote to the adult. Epigenetic changes in gene activity can be studied in relation to DNA methylation in cultured mammalian cells and it is also possible to isolate and characterize mutants with altered DNA methylase activity.

To a great extent for many biologists epigenetics at the end of the 20th-century could be reduced to the examination of methylation of DNA and histone modifications, two molecular mechanisms which are critical in the regulation of genes.

Perhaps the most well-known phenomenon in the public in relation to epigenetics is the intergenerational transmission of negative outcomes due to the Dutch famine of 1944–1945, though this phenomenon is far more well attested in nematode worms.

Today, many researchers are asserting that clarification of terminology is needed to clear up the muddle around epigenetics.

The Insight Show Notes — Season 2, Episode 26: The Epigenetics Revolution was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

May 7, 2019

The misunderstanding of epigenetics

Filed under: Epigenetics,Genetics,science — Razib Khan @ 11:15 pm
Conrad Waddington’s “epigenetic landscape”

In most graduate programs students must complete a series of oral exams or make a presentation to professors to “qualify” to proceed in their research. The goal here is to make sure that a student goes forward productively, rather than spending years flailing without direction.

Often the examination and review will involve both the research program that the student is specializing within and, general knowledge about the discipline in which they practice. A population geneticist may be asked to derive the coalescent. A molecular geneticist may be asked to sketch out the process of DNA replication.

Usually, all goes well. But sometimes there are unforeseen speed bumps.

One of my acquaintances did research which involved epigenetics for their Ph.D. During their qualifying examination, they were asked to describe some basic epigenetic mechanisms by one of their professors.

But, during the middle of the description, the examiners began to interrupt and it came to be understood that there were some fundamental disagreements as to what epigenetics was within the group of scientists!
A molecular biological view of epigenetics

How could such a thing happen? How can scientists actually disagree about what epigenetics entails? Especially in light of the fact that epigenetics is a scientifically vibrant topic, which has also been of interest to the public!

Sometimes single steps seem reasonable, but eventually, they lead you down a path into a tangled mess. The definition of epigenetics and its cultural evolution over the past 80 years is an example of that. It has mutated and diversified so that even within science people can mean different things when they say “epigenetics.”

The term was coined originally in 1942, by Conrad Waddington. He used it to define the whole set of processes which mediate how a genotype is translated into a phenotype. Basically, how is it that the information in genes leads to the diverse cells and tissues which define an organism. Waddington was deeply interested in processes of development and how that integrated into an evolutionary context. He was highly influential upon Stephen Jay Gould. But he wrote and was thinking well before the discovery of the structure of DNA.

Today, 70 years into the “DNA age”, many biologists have much more specific ideas, involving particular molecular biological mechanisms, in relation to epigenetics. Even though the cells of each human have the same DNA sequence, genes are expressed differently over time in different tissues. The DNA sequence in the cells of your liver is the same as the DNA sequence in the cells of your muscles, but clearly, the nature of these cells could not be more different. The tissues look different, and the physiological processes are quite different.

Depending on who you talk to (see above), epigenetics today operationally is an exploration of these mechanisms of the expression of DNA code which translate into the structures and processes that go into the creation of an organism. It is on top of the DNA layer of information that guides gene expression and organismal development (don’t be surprised if “histone modifications” get brought up if you talk to a biologist about epigenetics!).

Audrey Hepburn suffered malnutrition during the Dutch famine

Finally, there is the definition of epigenetics that has percolated into sensational popular treatments that it has transformed our understanding of Mendelian inheritance. That it is a scientific revolution. And, that environmental inputs can change one’s DNA, and those changes can be passed down to future generations.

One of the strangest things is the leveraging of this definition for marketing goods and services. Epigenetics is now big business. There are now health spas which claim epigenetic enhancement. There are skin creams which utilize the latest in epigenetics insights. Or so they say.

Much of the hype around epigenetics goes back to a study of the impact of the Dutch famine on the long-term health of those who suffered, and their descendants. The most sensational and impactful result of this study is that environmental stress may leave marks on genomes, which are then inherited by descendants of those who have suffered stress.

The implications from this fact are that “DNA is not destiny”, and that in your environment can impact your descendants through your DNA.

Though the study of the Dutch famine is legitimate science, most geneticists are highly skeptical of inter-generational transmission of epigenetic effects across generations in humans.

Even if this was a real phenomenon, the fact that Mendelian genetics was applicable to humans long before DNA was characterized indicates that very little of inheritance is perturbed by epigenetic effects.

The “epigenetics revolution” is more one of marketing than substance.

The biggest problem with epigenetics from the perspective of science communication is that it is an incredibly fertile and rich field of study, with important consequences in areas such as medicine, but its public perception is defined by a very specific phenomenon which many researchers are skeptical of. The impact of your smoking is going to affect your health. It is not going to have an effect on your descendants’ DNA though.

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

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.

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