Razib Khan One-stop-shopping for all of my content

October 28, 2017

Apes just being apes

Filed under: Genomics — Razib Khan @ 12:10 am

A while back I made from of bonobos and chimpanzees for being kind of losers for looking across at each other on either side of the Congo river for ~1.5 million years the time elapsed since their diversion. I finally ended up reading the paper from last year, Chimpanzee genomic diversity reveals ancient admixture with bonobos, which reported complex population history between these two species. In other words, “they got it on”.

The key was a reasonable sample size of N=40 and high coverage genomes (>20x), to give them the amount of information necessary to have the power to detect admixture. If you aren’t human and have a reasonable size genome, and all mammals do, get to the back of the line. But the Pan‘s turn finally arrived.

The paper primary result is that over past few hundred thousand years there have been reciprocal gene flow events of small, but detectable, magnitude between chimpanzees and bonobos. Naturally, there was some geographic specificity here, in that chimpanzees from far West Africa lack much evidence of this while those from Central Africa have a great deal. The admixture is directly proportional to proximity to b0nobo range.

To obtain the result their initial focus on high-frequency bonobo derived alleles that were at low to moderate frequencies in chimpanzees. There was a notable excess for this class among Central African chimpanzees. And, these alleles seem to have introgressed recently.

I suppose the major takeway is that hominids do it like they do it on the Discovery Channel.

October 22, 2017

Selection swimming against the genomic tide

Filed under: Africa Genetics,Africa Genomics,Genetics,Genomics — Razib Khan @ 1:32 pm

One of the major issues that confuses people is that the distribution of a trait or gene is often only weakly correlated with overall phylogeny and the rest of the genome.

To give a strange but classic example, the MHC loci are subject to strong balancing selection. This means that novel alleles do not substitute and replace ancestral alleles. Substitution of this sort results in “lineage sorting,” so that when you look at chimpanzees and humans you can see many polymorphic loci where all humans carry one variant and all chimpanzees the other. In contrast at the MHC loci there is frequency-dependent selection for rare variants, so the normal cycling process does not occur. Humans and chimpanzees overlap quite a bit on MHC, and any given human may have a more similar profile to a given chimpanzee than another human.

There are 19,000 human genes. At 3 billion base pairs only about ~100 million are polymorphic on a worldwide scale (using some liberal definitions). There are lots of unique stories to tell here.

A new preprint, Inferring adaptive gene-flow in recent African history, illustrates how certain genes with functional significance may differ from genome-wide background. The authors find that among the Fula (Fulani) people of West Africa there has been introgression from a Eurasian mutation that confers lactase persistence. The area of the genome around this gene is much more Eurasian than the rest of the genome. In contrast, the area around the Duffy allele is much less Eurasian. The variation in this locus is related to malaria resistance. Finally, in other African populations, they found gene flow of MHC variants.

None of this is entirely surprising, though the authors apply novel haplotype-based methods which should have wider utility.

September 10, 2017

Quantitative genomics, adaptation, and cognitive phenotypes

The human brain utilizes about ~20% of the calories you take in per day. It’s a large and metabolically expensive organ. Because of this fact there are lots of evolutionary models which focus on the brain. In Catching Fire: How Cooking Made Us Human Richard Wrangham suggests that our need for calories to feed our brain is one reason we started to use fire to pre-digest our food. In The Mating Mind Geoffrey Miller seems to suggest that all the things our big complex brain does allows for a signaling of mutational load. And in Grooming, Gossip, and the Evolution of Language Robin Dunbar suggests that it’s social complexity which is driving our encephalization.

These are all theories. Interesting hypotheses and models. But how do we test them? A new preprint on bioRxiv is useful because it shows how cutting-edge methods from evolutionary genomics can be used to explore questions relating to cognitive neuroscience and pyschopathology, Polygenic selection underlies evolution of human brain structure and behavioral traits:

…Leveraging publicly available data of unprecedented sample size, we studied twenty-five traits (i.e., ten neuropsychiatric disorders, three personality traits, total intracranial volume, seven subcortical brain structure volume traits, and four complex traits without neuropsychiatric associations) for evidence of several different signatures of selection over a range of evolutionary time scales. Consistent with the largely polygenic architecture of neuropsychiatric traits, we found no enrichment of trait-associated single-nucleotide polymorphisms (SNPs) in regions of the genome that underwent classical selective sweeps (i.e., events which would have driven selected alleles to near fixation). However, we discovered that SNPs associated with some, but not all, behaviors and brain structure volumes are enriched in genomic regions under selection since divergence from Neanderthals ~600,000 years ago, and show further evidence for signatures of ancient and recent polygenic adaptation. Individual subcortical brain structure volumes demonstrate genome-wide evidence in support of a mosaic theory of brain evolution while total intracranial volume and height appear to share evolutionary constraints consistent with concerted evolution…our results suggest that alleles associated with neuropsychiatric, behavioral, and brain volume phenotypes have experienced both ancient and recent polygenic adaptation in human evolution, acting through neurodevelopmental and immune-mediated pathways.

The preprint takes a kitchen-sink approach, throwing a lot of methods of selection at the phenotype of interest. Also, there is always the issue of cryptical population structure generating false positive associations, but they try to address it in the preprint. I am somewhat confused by this passage though:

Paleobiological evidence indicates that the size of the human skull has expanded massively over the last 200,000 years, likely mirroring increases in brain size.

From what I know human cranial sizes leveled off in growth ~200,000 years ago, peaked ~30,000 years ago, and have declined ever since then. That being said, they find signatures of selection around genes associated with ‘intracranial volume.’

There are loads of results using different methods in the paper, but I was curious note that schizophrenia had hits for ancient and recent adaptation. A friend who is a psychologist pointed out to me that when you look within families “unaffected” siblings of schizophrenics often exhibit deviation from the norm in various ways too; so even if they are not impacted by the disease, they are somewhere along a spectrum of ‘wild type’ to schizophrenic. In any case in this paper they found recent selection for alleles ‘protective’ of schizophrenia.

There are lots of theories one could spin out of that singular result. But I’ll just leave you with the fact that when you have a quantitative trait with lots of heritable variation it seems unlikely it’s been subject to a long period of unidirecitional selection. Various forms of balancing selection seem to be at work here, and we’re only in the early stages of understanding what’s going on. Genuine comprehension will require:

– attention to population genetic theory
– large genomic data sets from a wide array of populations
– novel methods developed by population genomicists
– and funcitonal insights which neuroscientists can bring to the table

July 26, 2017

The future will be genetically engineered

Filed under: Genetics,Genomics — Razib Khan @ 4:04 pm


If the film Rise of the Planet of the Apes had come out a few years later I believe there would have been mention of CRISPR. Sometimes science leads to technology, and other times technology aids in science. On occasion the two are one in the same.

The plot I made above shows that in the first five years of the second decade of the 20th century CRISPR went from being an obscure aspect of bacterial genetics to ubiquitous. Friends who had been utilizing “advanced” genetic engineering methods such as TALENS and zinc fingers switched overnight to a CRISPR/Cas9 framework.

As I’ve said before the 2010s are the decade when “reading” the genome becomes normal. We really don’t know what the CRISPR/Cas9 technology is capable of. It’s early years yet. With that, First Human Embryos Edited in U.S.. Technically they’re single celled zygotes. The science itself is not astounding. Rather, it is that the human rubicon has been passed in the United States. As indicated in the article there has been some jealousy about what the Chinese have been able to do because of a different cultural and regulatory framework.

There are those calling for a moratorium on this work (on humans). I’m not in favor or opposed. Rather, my question is simple: if CRISPR/Cas9 makes genetic engineering cheap, easy, and effective, how exactly are we going to enforce a world-wide moratorium? A Butlerian Jihad?

Note: I know that people are freaking about humans + genetic engineering. But most geneticists I know are more excited about the prospects of non-human work, since human clinical trials are going to be way in the future. Over 20 years since Dolly it’s notable to me that no human has been cloned from adult somatic cells yet.

June 27, 2017

Genome sequencing for the people is near

Filed under: Genomics,Personal genomics — Razib Khan @ 7:22 am

When I first began writing on the internet genomics was an exciting field of science. Somewhat abstruse, but newly relevant and well known due to the completion of the draft of the human genome. Today it’s totally different. Genomics is ubiquitous. Instead of a novel field of science, it is transitioning into a personal technology.

But life comes at you fast. For all practical purposes the $1,000 genome is here.

And yet we haven’t seen a wholesale change in medicine. What happened? Obviously a major part of it is polygenicity of disease. Not to mention that a lot of illness will always have a random aspect. People who get back a “clean” genome and live a “healthy” life will still get cancer.

Another issue is a chicken & egg problem. When a large proportion of the population is sequenced and phenotyped we’ll probably discover actionable patterns. But until that moment the yield is going to not be too impressive.

Consider this piece in MIT Tech, DNA Testing Reveals the Chance of Bad News in Your Genes:

Out of 50 healthy adults [selected from a random 100] who had their genomes sequenced, 11—or 22 percent—discovered they had genetic variants in one of nearly 5,000 genes associated with rare inherited diseases. One surprise is that most of them had no symptoms at all. Two volunteers had genetic variants known to cause heart rhythm abnormalities, but their cardiology tests were normal.

There’s another possible consequence of people having their genome sequenced. For participants enrolled in the study, health-care costs rose an average of $350 per person compared with a control group in the six months after they received their test results. The authors don’t know whether those costs were directly related to the sequencing, but Vassy says it’s reasonable to think people might schedule follow-up appointments or get more testing on the basis of their results.

Researchers worry about this problem of increased costs. It’s not a trivial problem, and one that medicine doesn’t have a response to, as patients often find a way to follow up on likely false positives. But it seems that this is a phase we’ll have to go through. I see no chance that a substantial proportion of the American population in the 2020s will not be sequenced.

May 15, 2017

Reason is but a slave of passions as it always has been

David Hume stated that “reason is, and ought only to be the slave of the passions.” I don’t know about the ought part, that’s up for debate. But the is part seems empirically true. The reasons people give for this or that is often just a post hoc rationalization. To give a different twist to this contention, others have argued that reason exists to win arguments, not converge upon truth. Or more precisely in my opinion to give the patina of erudition or abstraction to sentiments which are fundamentally derived from emotion or manners enforced through group norms (ergo, the common practice of ‘educated’ people citing scholars whose work we can’t evaluate to buttress our own preconceptions; we all do it).

One of the reasons I recommend In Gods We Trust, and cognitive anthropology more generally, to atheists and religious skeptics is that it gives a better empirical window into the mental processes that are really at work, as opposed to those which people say are at work (or, more unfortunately, those they think are at work). In In Gods We Trust the author reports on research conducted where religious believers are given a set of factual assertions purportedly from scholarship (e.g., the Dead Sea Scrolls). These assertions on the face of it flatly contradict their religious beliefs in some deep fundamental way. But when confronted with facts which seem to logically refute the coherency of their beliefs, they often still accept the validity of the scholarship before them. When asked about the impact on their beliefs? Respondents generally asserted that the new facts strengthened their beliefs.

This is one reason that cognitive anthropologists term religious ‘reasoning’ quasi-propositional. It takes the general form of analysis from axioms, but ultimately the rationality is besides the point, it is simply a quiver in the arrow of a broader and deeper cognitive phenomenon.

To give a personal example which illustrates this. Many many years ago I knew a Jewish girl of Modern Orthodox girl background passingly. She once asserted to me that the event of the Holocaust strengthened her belief in her God. I didn’t follow through on this discussion, as it was too disturbing to me. But it brought home to me that in some way the “reasoning” of many religious people leaves me totally befuddled (and no doubt vice versa).

As it happens, while in the course of writing this post, I found out that Hugo Mercier and Dan Sperber, the authors of the above argument in relation to reason and argumentation, published a book last month, The Enigma of Reason. I encourage readers to get it. I just bought a Kindle copy. Dan Sperber, who I interviewed 12 years ago, is a very deep thinker on the level of Daniel Kahneman. He’s French, and his prose can be somewhat difficult, so I wonder if that’s one reason he’s not nearly as well known).

Ultimately the point of this post actually goes back to genomics and history. Anne Gibbons has an excellent piece in Science, There’s no such thing as a ‘pure’ European—or anyone else. In it she draws on the most recent research in human population genomics to refute antiquated ideas about the purity of any given population. If you have read this blog for the past few years you already know most human populations are complex admixtures; that is, it isn’t a human family tree, but a human family graph.

Gibbons’ piece attacks directly some standard racialist talking points which have been refuted on a factual basis by genetic science:

When the first busloads of migrants from Syria and Iraq rolled into Germany 2 years ago, some small towns were overwhelmed. The village of Sumte, population 102, had to take in 750 asylum seekers. Most villagers swung into action, in keeping with Germany’s strong Willkommenskultur, or “welcome culture.” But one self-described neo-Nazi on the district council told The New York Times that by allowing the influx, the German people faced “the destruction of our genetic heritage” and risked becoming “a gray mishmash.”

In fact, the German people have no unique genetic heritage to protect. They—and all other Europeans—are already a mishmash, the children of repeated ancient migrations, according to scientists who study ancient human origins. New studies show that almost all indigenous Europeans descend from at least three major migrations in the past 15,000 years, including two from the Middle East. Those migrants swept across Europe, mingled with previous immigrants, and then remixed to create the peoples of today.

First, let’s set aside the political question of welcoming on the order of one million refugees to Germany. I will not post comments discussing that.

As a point of fact the truth genetically in relation to Germans is even more complex than what Gibbons’ asserts. When I worked with FamilyTree DNA I had access to their database and presented at their year conference some interesting results from people whose four grandparents were from Germany. In short, Germans tended to fall into three main clusters, one that was strongly skewed toward people from some parts of France, another which was shifted toward Scandinavians, and a third which was very similar to Slavs.

The historical and cultural reasons for this are easy to guess at or make conjectures. The takeaway here is that unlike Finns, or Irish, and to a great extent Scandinavians and Britons, Germany exhibits a lot of population substructure within it because of assimilation or migration in the last ~1,000 years. This is why genetically saying someone is “German” is very difficult when compared to saying someone is Polish or Swedish. By dint of their cultural expansiveness Germans are everyone and no one set next to other Northern Europeans* (with the exception perhaps of the French…I’m sure Germans will appreciate this comparison!).

The conceit of these sort of pieces is that racists will confront refutations which will shatter their racist axioms. But since most of the people who are writing these pieces and read Science are not racists, they won’t have a good intuition on the cognitive processes at work for genuine racists.

This causes problems. As a comparison, many atheists seem to think that refutation of the Athanasian creed will blow Christians away and make them forsake their God (or showing them contradictions in the Bible, admit that you’ve gone through that phase!). Though the Church Father Tertullian’s assertion that he “believed because it is absurd” is more subtle than I often make it out to be, on the face of it it does reflect how outsiders view a normative social group like Christianity.

The emphasis here is on normative. Social or religious movements and sentiments are often about norms, which emerge at the intersection of history, intuition, instinct, and facts. I place facts last in the list, because I think it is a defensible stance to take that facts are the least important variable!

The field of cultural evolution has shown that group cohesion and communal norms have been major drivers of human evolution. Likely there has been gene-cultural coevolution so that group conformity has been selected for as a way to make social units operate more smoothly. Social cognition is a thing; people believe what they believe because other people in their social groups believe something, not because they’ve reasoned to it themselves. Originally reasoning is hard. Letting others derive for you, and plugging and chugging is easy. As Muhammad stated, the Ummah will not agree upon error! The smarter people are, the better they are are reasoning…but the better they are at motivated reasoning, ignorance, and rationalization.

When faced with disconfirming evidence some people can dig in and deny the plain facts. Creationists are a straightforward case of this. Then there are evaders.  From what I have seen on the political Left in the United States at least over the last 15 years (when I’ve been engaging actively with people on the internet) there has been a consistent pattern of obfuscation and dodging the likely reality of sex differences in many quarters. When pinned down on the fundamentals few deny the principle or the possibility, but they almost always impose an extremely high level of skepticism that is not found in other domains, where their epistemology is far less stringent.

But then there is a third case, where facts that seem to refute on first blush to you  only strengthen the beliefs of someone with whom you already disagree. I am generally of the view that the rise of naturalistic science has probably undermined the case for classical supernaturalist theism, which emerged in the pre-modern era. Reasonable people can disagree, as I have smart religious friends who are also scientists. Some of these people, like Francis Collins, will even assert that modern findings which boggle the mind and shock our intuitions confirm and strengthen their belief in pre-modern religious systems!

My point is not to take a strong stance on science and religion. Rather, it is to say that when you present evidence and declare “I refute you thus!”, they may simply respond “Aha! You have proven my point!”

In relation to the Gibbons’ article the writing has been on the wall for at least three years, and probably longer. In Towards a new history and geography of human genes informed by ancient DNA Pickrell and Reich content:

…Implicit in this research is the assumption that the geographic locations of people today are informative about the geographic locations of their ancestors in the distant past. However, it is now clear that long-range migration, admixture and population replacement have been the rule rather than the exception in human history. In light of this, we argue that it is time to critically re-evaluate current views of the peopling of the globe and the importance of natural selection in determining the geographic distribution of phenotypes. We specifically highlight the transformative potential of ancient DNA. By accessing the genetic make-up of populations living at archaeologically-known times and places, ancient DNA makes it possible to directly track migrations and responses to natural selection.

Since this was published in spring of 2014 the evidence has gotten stronger and stronger. That is, the distribution of outcomes is getting more consistent and converging to a high confidence truth.

From this, are we to conclude that white nationalism would decline from marginal to non-existent in the past three years? A review of the empirical data does not seem to support that proposition. Therefore, a naive model that white nationalism is predicated on facts about racial purity may be wrong.

The responses that I have seen (often in the form of comments I don’t publish on this weblog) are denial/rejection, confusion, reinterpretation and vindication (along with standard issue racial insults directed toward me, their colored cognitive inferior). As with the religious case I have a difficult time “putting myself” in the shoes of a racialist of any sort, so I don’t totally understand how they’re getting from A to B, but in their own minds they are.

Let’s reaffirm what’s going on here: white racial consciousness in the United States has exploded on the public scene over the past three years, just as scientists have come to the very strong conclusion that the “white European race” as we understand it is an artifact of the last ~5,000 years or so.**

We need to go back to Hume, and the anthropological understanding of what reason is. Reason is a tool to confirm what you already hold to be true and good. If reason falsifies in some way what you hold to be true and good, that does not mean for most people that reason is where they will stand. Likely there will be some subtle reinterpretation, but magically reason will support their presuppositions. Ask the descendants of the followers of William Miller about falsification.

The fact is that very few people in the world know about David Reich and his research. I know this personally because I’m a voluble evangelist, and many geneticists, even human geneticists, are not aware of the revolution in historical population genetics that ancient DNA has wrought. I do not know any Nazis personally, I suspect that perhaps their knowledge of human phylogenomics is not at the same level as a typical geneticist.

Of course this sort of logic about logic cuts both ways. Before 2010 I actually assumed, as did most human geneticists who took an interest in these topics, that human populations had long been resident in their region of current occupation for tens of thousands of years. When I read Reconstructing Indian Population History by David Reich I was shocked out of my prior model, because the inferences were so ingenious and plausible, and, the updated story of how South Asians came to be actually made a lot of anomalies make a lot more sense. When Lazaridis et al. posted Ancient human genomes suggest three ancestral populations for present-day Europeans on biorxiv in the December of 2013 I was far more surprised, because I had always assumed that the thesis that most European ancestry dated to the Pleistocene in any given region was a robust one. Both the phylogeography from mtDNA and Y pointed to a Pleistocene origin.

But the data were compelling. It’s one thing to make inferences on present day genetic distribution, it’s another to actually genotype ancient individuals (remember, I can reanalyze the data myself, and have done so numerous times). Lazaridis et al. and Priya Moorjani’s Genetic Evidence for Recent Population Mixture in India totally changed my personal life. All of a sudden my wife and I were far closer emotionally and spiritually because we understood that the TMRCA of many segments in our autosomal genome was about 5-fold closer than I had assumed!!!***

Actually, the last sentence is a total fiction. The history which changed how I understood my wife and I to be related on a historical population genetic sense had zero impact on our relationship. That’s because we’re not racists, and race doesn’t really impact our relationship too much (the fact that my parents are Muslim, well, that’s a different issue….). Sorry Everyday Feminism. This is not an uncommon view, though perhaps not as common as we’d assumed of late (actually, as someone who has looked at the fascinating interracial dating research, I pretty much understood that what people say is quite different than what they do; anti-racism is the conformist thing to do, so people will play that tune for a while longer).

Just because the state of the world is one particular way, it does not naturally follow that it should be that way, or that it always will be that way. Most ethical religions saw in slavery an aspect of injustice; rational arguments aside, on some level extension of empathy and sympathy makes its injustice self-evident. But they accepted that it was an aspect of the world that was naturally baked into the structure of reality. The de jure abolition of slavery today does not mean it has truly gone away, but its practice has certainly been curtailed, and much of the cruelty diminished. Theories of human nature or necessities of economic production at the end of the day gave way changing mores and values. Facts about the world became less persuasive when we decided to let them no longer dictate tolerance of slavery.

All that I say above in relation to how humans use reason does not leave scientists or journalists untouched. All humans have their own goals, and even though they see through the glass darkly, they see in the visions beyond what they want to see. The cultural and theoretical structure of modern science is such that some of these impulses are dampened and human intuitions are channeled in a manner so that theories and models of the world seem to correspond to reality. But I believe this is deeply unnatural, and also deeply fragile. When moving outside of their domain of specialty scientists can be quite blind and irrational. Even when one steps away at a mild remove in terms of domain knowledge this becomes clear, such as when Linus Pauling promoted Vitamin C. And motivated reasoning can creep into the actions of even the greatest of scientists, such as when R. A. Fisher rejected the causal connection between tobacco and cancer.****

I will end on a frank and depressing note: I believe that the era of public reason and fealty to empirical standards in at least official capacities is fading. Social cognition, tribal logic, is on the rise. But we have to remember that in the historical perspective social cognition and tribal logic ruled the day. They are the norm. This is age when he abide by public reason is the peculiarity in the sea of polemic. Ultimately it may be the fool who fixates on being right or wrong, as opposed to being on the winning team. I hope I’m wrong on this.

Addendum: I have written a form of this post many times.

* The current chancellor of Germany has a Polish paternal grandfather.

** If Middle Easterners are included as white we can extended the time horizon much further back, but that seems to defeat the purpose of white nationalism in the United States….

*** I had assumed that the western affinity in South Asians had diverged from Europeans during the Last Glacial Maximum. In turns out some of it may be as recent as ~4,500 years ago or so.

**** This may have been unconsciously as opposed to malicious, as Fisher was keen on tobacco personally.

May 11, 2017

When conquered pre-Greece took captive her rude Hellene conqueror

Filed under: Genetics,Genomics,Greece,History,Migration — Razib Khan @ 12:22 am


When I was a child in the 1980s I was captivated by Michael Wood’s documentary In Search of the Trojan War (he also wrote a book with the same name). I had read a fair amount of Greek mythology, prose translations of the Iliad, as well as ancient history. The contrast between the Classical Greeks, the strangeness of their mythology was always something that on the surface of my mind. The reality that Bronze Age Greeks were very different from Classical Greeks resolved this issue to some extent.

Though Classical Greeks were very different from us, to some extent Western civilization began with them, and they are very familiar to us. Rebecca Goldstein’s Plato at the Googleplex was predicated on the thesis that the ancient Greek philosopher had something to tell us, and that if he was alive today he would be a prominent public speaker.

I’m going to dodge the issue of Julian Jaynes’ bicameral mind, and just assert that people of the Bronze Age were fundamentally different from us. And that difference is preserved in aspects of Greek mythology. Though it is fashionable, and correct, to assert that Homer’s world was not that of Mycenaeans, but the barbarian period of the Greek Dark Age, it is not entirely true. Homer clearly preserved traditions where citadels such as Mycenae and Pylos were preeminent, and details such as the boar’s tusk helmets are also present in the Iliad.

But aesthetic details or geopolitics are not what struck me about Greek mythology, but events such as the sacrifice of Iphigenia. Like Abraham’s near sacrifice of his son, this plot element strikes moderns as cruel, barbaric, and unthinking. And though the Classical Greeks did not have our conception of human rights, they had turned against human sacrifice (and the Romans suppressed the practice when they conquered the Celts) on the whole, but it seems to have occurred in earlier periods.

The rupture between the world of the Classical Greeks and the strange edifices of Mycenaean Greece were such that scholars were shocked that the Linear B tablets of the Bronze Age were written in Greek when they were finally deciphered. In fact many of the names and deities on these tablets would be familiar to us today; the name Alexander and the goddess Athena are both attested to in Mycenaean tablets.

Preceding the Mycenaeans, who  emerge in the period between 1400-1600 BCE, are the Minoans, who seem to have developed organically in the Aegean in the 3rd millennium. This culture had relations with Egypt and the Near East, their own system of writing, and deeply influenced the motifs of the successor Mycenaean Greek civilization. The aesthetic similarities between Mycenaeans and Minoans is one reason that many were surprised that the former were Greek, because the Minoan language was likely not.

Mycenaean civilization seems to have been a highly militarized and stratified society. There is a reason that this is sometimes referred to as the “age of citadels.” Allusions to the Greeks, or Achaeans, in the diplomatic missives of the Egyptians and Hittites suggests that the lords of the Hellenes were reaver kings. In 1177 B.C. Eric Cline repeats the contention that a fair portion of the “sea peoples” who ravaged Egypt in the late Bronze Age were actually Greeks.

So when did these Greeks arrive to the shores of Hellas? In The Coming of the Greeks Robert Drews argued that the Greeks were part of a broader movement of mobile charioteers who toppled antique polities and turned them into their own. The Hittites and Mitanni were two examples of Indo-European ruling elites who took over a much more advanced civilizational superstructure and made it their own. While the Hittites and other Indo-Europeans, such as the Luwians and Armenians, slowly absorbed the non-Indo-European substrate of Anatolia, the Indo-Aryan Mitanni elite were linguistically absorbed by their non-Indo-European Hurrian subjects. Indo-Aryan elements persisted only their names, their gods, and tellingly, in a treatise on training horses for charioteers.

Drews’ thesis is that the Greek language percolated down from the warlords of the citadels and their retinues over the Bronze Age, with the relics who did not speak Greek persisting into the Classical period as the Pelasgians. Set against this is the thesis of Colin Renfrew that Greece was one of the first Indo-European languages, as Indo-European languages began in Anatolia.

The most recent genetic data suggest to me that both theses are likely to be wrong. The data are presented in two preprints The Population Genomics Of Archaeological Transition In West Iberia and The Genomic History Of Southeastern Europe. The two papers cover lots of different topics. But I want to focus on one aspect: gene flow from steppe populations into Southern Europe.

We know that in the centuries after 2900 BCE there was a massive eruption of individuals from the steppe fringe of Eastern Europe, and Northern Europe from Ireland to to Poland was genetically transformed. Though there was some assimilation of indigenous elements, it looks to be that the majority element in Northern Europe were descended from migrants.

For various reasons this was always less plausible for Southern Europe. The first reason is that Southern Europeans shared a lot of genetic similarities to Sardinians, who resembled Neolithic farmers. Admixture models generally suggested that in the peninsulas of Southern Europe the steppe-like ancestry was the minority component, not the majority, as was the case in Northern Europe.

These data confirm it. The Bronze Age in Portugal saw a shift toward steppe-inflected populations, but it was not a large shift. There seems to have been later gene flow too. But by and large the Iberian populations exhibit some continuity with late Neolithic populations.  This is not the case in Northern Europe.

In The Genomic History Of Southeastern Europe the authors note that steppe-like ancestry could be found sporadically during early periods, but that there was a notable increase in the Bronze Age, and later individuals in the Bronze Age had a higher fraction. Nevertheless, by and large it looks as if the steppe-like gene flow in the southerly Balkans (focusing on Bulgarian samples) was modest in comparison to the northern regions of Europe. Unfortunately I do not see any Greece Bronze Age samples, but it seems likely that steppe-like influence came into these groups after they arrived in Bulgaria, which is more northerly.

Down to the present day a non-Indo-European language, Basque, is spoken in Spain. Paleo-Sardinian survived down to the Classical period, and it too was not Indo-European. Similarly, non-Indo-European Pelasgian communities continued down to the period of city-states in Greece.

These long periods of coexistence point to the demographic equality (or even superiority) of the non-Indo-European populations. The dry climate of the Mediterranean peninsulas are not as suitable for cattle based agro-pastoralism. This may have limited the spread and dominance of Indo-Europeans. Additionally, the Mediterranean peninsulas were likely touched by Indo-European migrations relatively late. Much of the early zeal for expansion may have already dissipated by them. The high frequency of likely Indo-European R1b lineages among the Basques is curious, and may point to the spreading of male patronization networks, and their assimilation into non-Indo-European substrates where necessary. R1b is also found in Sardinia, and in high frequencies in much of Italy.

The interaction and synthesis between native and newcomer was likely intensive in the Mediterranean. For example, of the gods of the Greek pantheon only Zeus is indubitably of Indo-European origin. Some, such as Artemis, have clear Near Eastern antecedents. But other Greek gods may come down from the pre-Greek inhabitants of what became Greece.

Ultimately these copious interactions and transformations should not be a great surprise. The sunny lands of the Mediterranean attracted Northern European tribes during Classical antiquity. The Cimbri invasion of Italy, Galatians in Thrace and Anatolia, the folk wandering of Vandals and Goths into Iberia, are all instances of population movements southward. These likely moved the needle ever so slightly toward convergence between Northern and Southern Europe in terms of genetic content.

In relation to the more general spread of Indo-Europeans, I believe there are a few areas like Northern Europe, where replacement was preponderant (e.g., the Tarim basin). But I also believe there were many more which presented a Southern European model of synthesis and accommodation.

When conquered pre-Greece took captive her rude Hellene conqueror

Filed under: Genetics,Genomics,Greece,History,Migration — Razib Khan @ 12:22 am


When I was a child in the 1980s I was captivated by Michael Wood’s documentary In Search of the Trojan War (he also wrote a book with the same name). I had read a fair amount of Greek mythology, prose translations of the Iliad, as well as ancient history. The contrast between the Classical Greeks, the strangeness of their mythology was always something that on the surface of my mind. The reality that Bronze Age Greeks were very different from Classical Greeks resolved this issue to some extent.

Though Classical Greeks were very different from us, to some extent Western civilization began with them, and they are very familiar to us. Rebecca Goldstein’s Plato at the Googleplex was predicated on the thesis that the ancient Greek philosopher had something to tell us, and that if he was alive today he would be a prominent public speaker.

I’m going to dodge the issue of Julian Jaynes’ bicameral mind, and just assert that people of the Bronze Age were fundamentally different from us. And that difference is preserved in aspects of Greek mythology. Though it is fashionable, and correct, to assert that Homer’s world was not that of Mycenaeans, but the barbarian period of the Greek Dark Age, it is not entirely true. Homer clearly preserved traditions where citadels such as Mycenae and Pylos were preeminent, and details such as the boar’s tusk helmets are also present in the Iliad.

But aesthetic details or geopolitics are not what struck me about Greek mythology, but events such as the sacrifice of Iphigenia. Like Abraham’s near sacrifice of his son, this plot element strikes moderns as cruel, barbaric, and unthinking. And though the Classical Greeks did not have our conception of human rights, they had turned against human sacrifice (and the Romans suppressed the practice when they conquered the Celts) on the whole, but it seems to have occurred in earlier periods.

The rupture between the world of the Classical Greeks and the strange edifices of Mycenaean Greece were such that scholars were shocked that the Linear B tablets of the Bronze Age were written in Greek when they were finally deciphered. In fact many of the names and deities on these tablets would be familiar to us today; the name Alexander and the goddess Athena are both attested to in Mycenaean tablets.

Preceding the Mycenaeans, who  emerge in the period between 1400-1600 BCE, are the Minoans, who seem to have developed organically in the Aegean in the 3rd millennium. This culture had relations with Egypt and the Near East, their own system of writing, and deeply influenced the motifs of the successor Mycenaean Greek civilization. The aesthetic similarities between Mycenaeans and Minoans is one reason that many were surprised that the former were Greek, because the Minoan language was likely not.

Mycenaean civilization seems to have been a highly militarized and stratified society. There is a reason that this is sometimes referred to as the “age of citadels.” Allusions to the Greeks, or Achaeans, in the diplomatic missives of the Egyptians and Hittites suggests that the lords of the Hellenes were reaver kings. In 1177 B.C. Eric Cline repeats the contention that a fair portion of the “sea peoples” who ravaged Egypt in the late Bronze Age were actually Greeks.

So when did these Greeks arrive to the shores of Hellas? In The Coming of the Greeks Robert Drews argued that the Greeks were part of a broader movement of mobile charioteers who toppled antique polities and turned them into their own. The Hittites and Mitanni were two examples of Indo-European ruling elites who took over a much more advanced civilizational superstructure and made it their own. While the Hittites and other Indo-Europeans, such as the Luwians and Armenians, slowly absorbed the non-Indo-European substrate of Anatolia, the Indo-Aryan Mitanni elite were linguistically absorbed by their non-Indo-European Hurrian subjects. Indo-Aryan elements persisted only their names, their gods, and tellingly, in a treatise on training horses for charioteers.

Drews’ thesis is that the Greek language percolated down from the warlords of the citadels and their retinues over the Bronze Age, with the relics who did not speak Greek persisting into the Classical period as the Pelasgians. Set against this is the thesis of Colin Renfrew that Greece was one of the first Indo-European languages, as Indo-European languages began in Anatolia.

The most recent genetic data suggest to me that both theses are likely to be wrong. The data are presented in two preprints The Population Genomics Of Archaeological Transition In West Iberia and The Genomic History Of Southeastern Europe. The two papers cover lots of different topics. But I want to focus on one aspect: gene flow from steppe populations into Southern Europe.

We know that in the centuries after 2900 BCE there was a massive eruption of individuals from the steppe fringe of Eastern Europe, and Northern Europe from Ireland to to Poland was genetically transformed. Though there was some assimilation of indigenous elements, it looks to be that the majority element in Northern Europe were descended from migrants.

For various reasons this was always less plausible for Southern Europe. The first reason is that Southern Europeans shared a lot of genetic similarities to Sardinians, who resembled Neolithic farmers. Admixture models generally suggested that in the peninsulas of Southern Europe the steppe-like ancestry was the minority component, not the majority, as was the case in Northern Europe.

These data confirm it. The Bronze Age in Portugal saw a shift toward steppe-inflected populations, but it was not a large shift. There seems to have been later gene flow too. But by and large the Iberian populations exhibit some continuity with late Neolithic populations.  This is not the case in Northern Europe.

In The Genomic History Of Southeastern Europe the authors note that steppe-like ancestry could be found sporadically during early periods, but that there was a notable increase in the Bronze Age, and later individuals in the Bronze Age had a higher fraction. Nevertheless, by and large it looks as if the steppe-like gene flow in the southerly Balkans (focusing on Bulgarian samples) was modest in comparison to the northern regions of Europe. Unfortunately I do not see any Greece Bronze Age samples, but it seems likely that steppe-like influence came into these groups after they arrived in Bulgaria, which is more northerly.

Down to the present day a non-Indo-European language, Basque, is spoken in Spain. Paleo-Sardinian survived down to the Classical period, and it too was not Indo-European. Similarly, non-Indo-European Pelasgian communities continued down to the period of city-states in Greece.

These long periods of coexistence point to the demographic equality (or even superiority) of the non-Indo-European populations. The dry climate of the Mediterranean peninsulas are not as suitable for cattle based agro-pastoralism. This may have limited the spread and dominance of Indo-Europeans. Additionally, the Mediterranean peninsulas were likely touched by Indo-European migrations relatively late. Much of the early zeal for expansion may have already dissipated by them. The high frequency of likely Indo-European R1b lineages among the Basques is curious, and may point to the spreading of male patronization networks, and their assimilation into non-Indo-European substrates where necessary. R1b is also found in Sardinia, and in high frequencies in much of Italy.

The interaction and synthesis between native and newcomer was likely intensive in the Mediterranean. For example, of the gods of the Greek pantheon only Zeus is indubitably of Indo-European origin. Some, such as Artemis, have clear Near Eastern antecedents. But other Greek gods may come down from the pre-Greek inhabitants of what became Greece.

Ultimately these copious interactions and transformations should not be a great surprise. The sunny lands of the Mediterranean attracted Northern European tribes during Classical antiquity. The Cimbri invasion of Italy, Galatians in Thrace and Anatolia, the folk wandering of Vandals and Goths into Iberia, are all instances of population movements southward. These likely moved the needle ever so slightly toward convergence between Northern and Southern Europe in terms of genetic content.

In relation to the more general spread of Indo-Europeans, I believe there are a few areas like Northern Europe, where replacement was preponderant (e.g., the Tarim basin). But I also believe there were many more which presented a Southern European model of synthesis and accommodation.

May 9, 2017

The Beaker is breaking!

The link is up, The Beaker Phenomenon And The Genomic Transformation Of Northwest Europe, but the paper is still processing:

I’ll update the post when I can read the paper.

May 6, 2017

Synergistic epistasis as a solution for human existence

Filed under: epistasis,Evolution,Evolutionary Genetics,Genetics,Genomics — Razib Khan @ 12:16 am

Epistasis is one of those terms in biology which has multiple meanings, to the point that even biologists can get turned around (see this 2008 review, Epistasis — the essential role of gene interactions in the structure and evolution of genetic systems, for a little background). Most generically epistasis is the interaction of genes in terms of producing an outcome. But historically its meaning is derived from the fact that early geneticists noticed that crosses between individuals segregating for a Mendelian characteristic (e.g., smooth vs. curly peas) produced results conditional on the genotype of a secondary locus.

Molecular biologists tend to focus on a classical, and often mechanistic view, whereby epistasis can be conceptualized as biophysical interactions across loci. But population geneticists utilize a statistical or evolutionary definition, where epistasis describes the extend of deviation from additivity and linearity, with the “phenotype” often being fitness. This goes back to early debates between R. A. Fisher and Sewall Wright. Fisher believed that in the long run epistasis was not particularly important. Wright eventually put epistasis at the heart of his enigmatic shifting balance theory, though according to Will Provine in Sewall Wright and Evolutionary Biology even he had a difficult time understanding the model he was proposing (e.g., Wright couldn’t remember what the different axes on his charts actually meant all the time).

These different definitions can cause problems for students. A few years ago I was a teaching assistant for a genetics course, and the professor, a molecular biologist asked a question about epistasis. The only answer on the key was predicated on a classical/mechanistic understanding. But some of the students were obviously giving the definition from an evolutionary perspective! (e.g., they were bringing up non-additivity and fitness) Luckily I noticed this early on and the professor approved the alternative answer, so that graders would not mark those using a non-molecular answer down.

My interested in epistasis was fed to a great extent in the middle 2000s by my reading of Epistasis and the Evolutionary Process. Unfortunately not too many people read this book. I believe this is so because when I just went to look at the Amazon page it told me that “Customers who viewed this item also viewed” Robert Drews’ The End of the Bronze Age. As it happened I read this book at about the same time as Epistasis and the Evolutionary Process…and to my knowledge I’m the only person who has a very deep interest in statistical epistasis and Mycenaean Greece (if there is someone else out there, do tell).

In any case, when I was first focused on this topic genomics was in its infancy. Papers with 50,000 SNPs in humans were all the rage, and the HapMap paper had literally just been published. A lot has changed.

So I was interested to see this come out in Science, Negative selection in humans and fruit flies involves synergistic epistasis (preprint version). Since the authors are looking at humans and Drosophila and because it’s 2017 I assumed that genomic methods would loom large, and they do.

And as always on the first read through some of the terminology got confusing (various types of statistical epistasis keep getting renamed every few years it seems to me, and it’s hard to keep track of everything). So I went to Google. And because it’s 2017 a citation of the paper and further elucidation popped up in Google Books in Crumbling Genome: The Impact of Deleterious Mutations on Humans. Weirdly, or not, the book has not been published yet. Since the author is the second to last author on the above paper it makes sense that it would be cited in any case.

So what’s happening in this paper? Basically they are looking to reduced variance of really bad mutations because a particular type of epistasis amplifies their deleterious impact (fitness is almost always really hard to measure, so you want to look at proxy variables).

Because de novo mutations are rare, they estimate about 7 are in functional regions of the genome (I think this may be high actually), and that the distribution should be Poisson. This distribution just tells you that the mean number of mutations and the variance of the the number of mutations should be the same (e.g., mean should be 5 and variance should 5).

Epistasis refers (usually) to interactions across loci. That is, different genes at different locations in the genome. Synergistic epistasis means that the total cumulative fitness after each successive mutation drops faster than the sum of the negative impact of each mutation. In other words, the negative impact is greater than the sum of its parts. In contrast, antagonistic epistasis produces a situation where new mutations on the tail of the distributions cause a lower decrement in fitness than you’d expect through the sum of its parts (diminishing returns on mutational load when it comes to fitness decrements).

These two dynamics have an effect the linkage disequilibrium (LD) statistic. This measures the association of two different alleles at two different loci. When populations are recently admixed (e.g., Brazilians) you have a lot of LD because racial ancestry results in lots of distinctive alleles being associated with each other across genomic segments in haplotypes. It takes many generations for recombination to break apart these associations so that allelic state at one locus can’t be used to predict the odds of the state at what was an associated locus. What synergistic epistasis does is disassociate deleterious mutations. In contrast, antagonistic epistasis results in increased association of deleterious mutations.

Why? Because of selection. If a greater number of mutations means huge fitness hits, then there will strong selection against individuals who randomly segregate out with higher mutational loads. This means that the variance of the mutational load is going to lower than the value of the mean.

How do they figure out mutational load? They focus on the distribution of LoF mutations. These are extremely deleterious mutations which are the most likely to be a major problem for function and therefore a huge fitness hit. What they found was that the distribution of LoF mutations exhibited a variance which was 90-95% of a null Poisson distribution. In other words, there was stronger selection against high mutation counts, as one would predict due to synergistic epistasis.

They conclude:

Thus, the average human should carry at least seven de novo deleterious mutations. If natural selection acts on each mutation independently, the resulting mutation load and loss in average fitness are inconsistent with the existence of the human population (1 − e−7 > 0.99). To resolve this paradox, it is sufficient to assume that the fitness landscape is flat only outside the zone where all the genotypes actually present are contained, so that selection within the population proceeds as if epistasis were absent (20, 25). However, our findings suggest that synergistic epistasis affects even the part of the fitness landscape that corresponds to genotypes that are actually present in the population.

Overall this is fascinating, because evolutionary genetic questions which were still theoretical a little over ten years ago are now being explored with genomic methods. This is part of why I say genomics did not fundamentally revolutionize how we understand evolution. There were plenty of models and theories. Now we are testing them extremely robustly and thoroughly.

Addendum: Reading this paper reinforces to me how difficult it is to keep up with the literature, and how important it is to know the literature in a very narrow area to get the most out of a paper. Really the citations are essential reading for someone like me who just “drops” into a topic after a long time away….

Citation: ScienceNegative selection in humans and fruit flies involves synergistic epistasis.

May 4, 2017

Africa’s great demographic transformation

Filed under: Bantu Expansion,Genetics,Genomics — Razib Khan @ 9:56 pm

Stonehenge has been a preoccupation for moderns since the Victorian period. It was built over 5,000 years ago, and its usage in some fashion continued down to about 2,500 years ago. For a long while it had been associated with the Celts, but more recently there has been some suspicion that its roots must be pre-Celtic.

And that is almost certainly true. The original site of Stonehenge had a wooden structure. But during the arrival of the Bell Beaker culture it was extensively rebuilt, and eventually stone monoliths were erected in the fashion we are used to seeing today.

Bernard Cornwell’s novel Stonehenge deals with this period. There is no major focus on physical conflict between the native populations, and the Bell Beaker groups. Rather, the plot centers around the cultural tumult and innovation that was triggered by the arrival of the newcomers.

In Stonehenge the Bell Beakers occupied more marginal, out of the way, territory. The novel presumed that ultimately there would be cultural fusion between the two groups, as there was a lot of interaction inter-personally among the characters of the two groups. We now know that the reality was likely one of near total replacement. From the abstract to be presented on shortly on the Bell Beakers:

British individuals associated with Beakers are genetically indistinguishable from continental individuals associated with the same material culture and genetically nearly completely discontinuous with the previously resident population.

This is not entirely surprising. Ancient Ireland seems to have been characterized by discontinuity with the arrival of Bell Beakers genetically.

Ancient DNA is not magic. But it can literally put some flesh on the bones of cultural shifts that archaeologists have seen in the material culture. One key element here is that the predominant ancestry across the British Isles today derives from migrations that date to the early Bronze Age.* I do not know if this has any relevance as to the arrival of the Celtic languages to the Britain and Ireland, but I suspect it does.

This was percolating in my mind because there’s a new paper which attempts to explore in more detail the Bantu expansions which occurred between 1000 BCE and 500 CE. It’s pretty incredible that from Gabon to Capetown Africans speak one language family, with similarities at least as close as that of the Romance language family.

But then is it incredible? Indo-European languages span the North Sea to the Bay of Bengal. The Bantu expansion in some ways serves as a template for the argument in First Farmers, as an agricultural revolution triggered a demographic expansion which did not stop until they reached the their geographic limits.

The paper in Science, which is open access, Dispersals and genetic adaptation of Bantu-speaking populations in Africa and North America, focuses on two issues. First, the demographic history and phylogenomics of the Bantu populations. Second, using population genomic methods it explores the dynamics of natural selection in these peoples. They utilize and extensive SNP data set, with more than 500,000 markers in their core analyses.

In general I think there are lots of interesting results in this paper. But the one angle I was unsatisfied by was their purported increase in coverage. As you can see it’s highly localized to a few countries. This is probably common sense since much of Africa is not accessible due to political issues (e.g., sampling in the Democratic Republic of Congo is treacherous right now). But one always has to be careful of the limitations of the data when making inferences. Though they have samples from the southwest (Angola, Namibia), the the African Great Lakes region around Uganda, and in South Africa, huge zones between are missing. And, they are highly over sampled in and around Gabon.

With all that said, I think with a variety of methods they probably have confirmed a major aspect of Bantu migration. I’ll quote:

Two hypotheses have been proposed concerning the dispersal of Bantu-speaking populations across sub-Saharan Africa (2–4). According to the “early-split” hypothesis, the western and eastern branches split early, within the Bantu heartland, into separate migration routes. By contrast, the “late-split” model suggests an initial spread southward from the Bantu homeland into the equatorial rainforest (i.e., Gabon/Angola), followed by expansions toward the rest of the subcontinent. We tested these hypotheses by determining whether eBSPs and seBSPs were genetically closer to wBSPs from the southern part, relative to wBSPs from the northern part, of western central Africa….

…Although additional sampling of African populations may further refine these patterns, our results, together with previous genetic data supporting the late-split model (2, 3), indicate that BSPs [Bantu-speaking peoples] first moved southward through the rainforest before migrating toward eastern and southern Africa, where they admixed with local populations. This model is further supported by linguistics (15) and archaeoclimate data (16), suggesting that a climatic crisis ~2500 years ago fragmented the rainforest into patches and facilitated the early movements of BSPs farther southward from their original homeland.

That being said, their sample limitations produce interesting assertions. E.g., “The GLOBETROTTER method estimated that eBSPs resulted from two consecutive admixture events (P < 0.05) occurring 1000 to 1500 years ago and 150 to 400 years ago between a wBSP (~75% contribution) and an Afroasiatic-speaking population from Ethiopia (~10% contribution).” GLOBETROTTER is powerful, but too often people use it in a manner where they assume that the inferences it generates from the data it has are the truth, as opposed to the closest GLOBETROTTER can get to the truth with the tools its given.

In this case I would contend that because there aren’t any Nilotic samples it leaves a major hole in their power to be able to accurately infer what really happened. The presence of pastoralist Nilotic people in close proximity to Bantu agriculturalists has been one of the major dynamics which define the East African landscape. The admixture into eastern Bantu agriculturalists therefore is almost certainly from Nilotic peoples, though there has been Afro-Asiatic (Cushitic) influence as far south as Tanzania, evident in enigmatic peoples such as the Sandawe.

The point here is that just because the GLOBETROTTER method inferred gene flow from a population in the sample set, it does not mean that the gene flow was necessarily from that population. The sampling of the region is sparse, so obviously this is only a first approximation. To some extent I assume the authors assume the readers will connect the dots, but often this sort of thing gets lost in translation, and then it gets into the media….

Though it is difficult to make in the admixture plot above, there are subtle differences in the eastern Bantu groups. The Luyha, who are from Kenya, do not show evidence of the blue component which is clearly Eurasian, while the Bakiga from Rwanda do. But even in the Bakiga the ratio of the violet element that seems to be associated with an indigenous African component which is distinct from that of the Bantu and the blue Eurasian is far higher than in the Afro-Asiatic populations in their data set (this does not mean they don’t have Eurasian ancestry, since admixture plots aren’t perfect proxies).

Because of the nature of the sampling and the utilization of admixture to frame their results I do feel that we don’t get a good sense of the variation among the Bantu across their full range. Granted, the between population genetic distance is actually quite low across this zone, on the order of 0.01, because of the recent shared ancestry. Africans may have much greater total diversity than Eurasians in their genomes, but their between population distance is actually not much different or even lower than Eurasians because of the recent demographic expansions. But did the Bantu expand into empty lands? The Khoisan, Pygmy and Nilotic (I’m sure that’s what it is) contribution to the Bantus across their range is clear, but that’s because we have close enough reference populations to model this contribution. What about areas like Tanzania? Or Mozambique? Were they empty? I suspect the issue here is that we don’t have any non-Bantu indigenous groups as they’ve all been absorbed.

But it is in the selection component that they offer a possible way to ascertain non-Bantu ancestry from ghost populations in the future. They found lots and lots of selection around immune genes. This is not surprising. There were local diseases which they had to adapt to. Therefore, “the HLA region in wBSPs showed a strong excess of ancestry from rainforest hunter-gatherers, at 38%, 6.74 SD higher than the genome-wide average of 16%…..”

In places like Mozambique it would be curious if the regions known to be under selection or enriched for indigenous ancestry in other areas where there are still indigenous populations exhibited a higher Fst against other groups. That is, the Mozambique ghost populations should leave an inordinate impact on regions of the genome associated with immunological function.

Which brings me back to Stonehenge. We do have ancient genomes. But not that many. Especially further back. Apparently the names of rivers and mountains often have very deep histories. For example, the river Humber has a name which may date back to pre-Celtic times (consider the Mississippi river, which has an American Indian origin). These serve as shadows of cultures long gone and replaced. The Bantu expansion is close enough to the margins of history that we don’t have so much time interposed between it and concrete records. We can skein out its outlines with more rigor and surety. And the patterns we see among the Bantus can give us a sense of how past demographic-cultural expansions may have occurred.

* The papers coming out of the PoBI project suggest that a significant minority of the ancestry in eastern England is Anglo-Saxon. But only there.

Addendum: I can’t find the data to download and test some things myself.

May 1, 2017

So what’s point of demographic models which leave you scratching your head

Filed under: Genomics,History,Human Genetics,Selection,Tibetans — Razib Khan @ 10:45 pm


There’s a new paper on Tibetan adaptation to high altitudes, Evolutionary history of Tibetans inferred from whole-genome sequencing. The focus of the paper is on the fact that more genes than have previously been analyzed seem to be the targets of natural selection. And I buy most of their analyses (not sure about the estimate of Denisovan ancestry being 0.4%…these sorts of things can be tricky).

But they fancy it up with a ∂a∂ model of population history, as well as using MSMC to account for gene flow. I don’t understand why they didn’t use something simpler like TreeMix, which can also handle more complex models. I guess because they wanted to focus on only a few populations?

Years ago I asked the developer of MSMC, Stephan Schiffels, if assuming an admixed population is not admixed might cause weird inferences. Why yes, it would. For example, admixed populations might show higher effective population since they’re pooling the histories of two separate populations. As for ∂a∂, the model above leaves me literally scratching my head.

…predicted that the initial divergence between Han and Tibetan was much earlier, at 54kya (bootstrap 95% C.I 44 kya to 58 kya). However, for the first 45ky, the two populations maintained substantial gene flow (6.8×10-4 and 9.0×10-4 per generation per chromosome). After 9.4 kya (bootstrap 95% C.I 8.6 kya to 11.2 kya), the gene flow rate dramatically dropped (1.3×10-11 and 4×10-7 per generation per chromosome), which is consistent with the estimate from MSMC.

Mystifying. The separation between Chinese and Tibetans is pretty much immediately after modern humans arrive in East Asia. Then there’s a lot of reciprocal gene flow…which ends during the Holocene.

We’re being told here that there are two populations which persisted in some form for ~45,000 years. Is this believable? That these two populations maintained some sort of continuity, and, remained in close proximity to engage in gene flow. And then ~10,000 years ago the ancestors of the Tibetans separated from the ancestors of the modern Han Chinese.

The latter scenario I can imagine. It’s this ~45,000 year dance I’m confused by. If there is substantial gene flow between the two groups why did they keep enough distinctive drift to be separate populations?

With what we know about ancient DNA from Europe if we posited such a model for that continent we’d be way off. There’s been too many population turnovers. Is East Asia different? I’m moderately skeptical of that. I think perhaps researchers should be very aware of the limitations of ∂a∂ when it comes to fine-grained population genomic analyses.

Note: This is a cool paper, and this small section is not entirely relevant. Which is why I’m confused about it since it seems the weakest part of the analysis in terms of originality, and the least believable.

April 28, 2017

Beyond “Out of Africa” and multiregionalism: a new synthesis?

Filed under: Africa,Evolution,Genetics,Genomics,Human Evolution,Human Genetics — Razib Khan @ 4:14 pm

For several decades before the present era there have been debates between proponents of the recent African origin of modern humans, and the multiregionalist model. Though molecular methods in a genetic framework have come of the fore of late these were originally paleontological theories, with Chris Stringer and Milford Wolpoff being the two most prominent public exponents of the respective paradigms.

Oftentimes the debate got quite heated. If you read books from the 1990s, when multiregionalism in particular was on the defensive, there were arguments that the recent out of Africa model was more inspirational in regards to our common humanity. As a riposte the multiregionalists asserted that those suggesting recent African origins with total replacement was saying that our species came into being through genocide.

Though some had long warned against this, the dominant perception outside of population genetics was that results such the “mitochondrial Eve” had given strong support to the recent African origin of modern humans, to the exclusion of other ancestry. 2002’s Dawn of Human Culture took it for granted that the recent African origin of modern humans to the total exclusion of other hominin lineages was established fact.

In 2008 I went to a talk where Svante Paabo presented some recent Neanderthal ancient mtDNA work. It was rather ho-hum, as Paabo showed that the Neanderthal lineages were highly diverged from modern ones, and did not leave any descendants. Though of course most modern human lineages did not leave any descendants from that period, Paabo took this evidence supporting the proposition that Neanderthals did not contribute to the modern human gene pool.

When his lab reported autosomal Neanderthal admixture in 2010, it was after initial skepticism and shock internally. I know Milford Wolpoff felt vindicated, while Chris Stringer began to emphasize that the recent African origin of modern humanity also was defined by regional assimilation of other lineages. The data have ultimately converged to a position somewhere between the extreme models of total replacement or balanced and symmetrical gene flow.

This is not surprising. Extreme positions are often rhetorically useful and popular when there’s no data. But reality does not usually conform to our prejudices, so ultimately one has to come down at some point.

The data for non-Africans is rather unequivocal. The vast majority of (>90%) of the ancestry of non-Africans seems to go back to a small number of common ancestors ~60,000 years ago. Perhaps in the range of ~1,000 individuals. These individuals seem to be a node within a phylogenetic tree where all the other branches are occupied by African populations. Between this period and ~15,000 years ago these non-Africans underwent a massive range expansion, until modern humans were present on all continents except Antarctica. Additionally, after the Holocene some of these non-African groups also experienced huge population growth due to intensive agricultural practice.

To give a sense of what I’m getting at, the bottleneck and common ancestry of non-Africans goes back ~60,000 years, but the shared ancestry of Khoisan peoples and non-Khoisan peoples goes back ~150,000-200,000 years. A major lacunae of the current discussion is that often the dynamics which characterize non-Africans are assumed to be applicable to Africans. But they are not.

A 2014 paper illustrates one major difference by inferring effective population from whole genomes: African populations have not gone through the major bottleneck which is imprinted on the genomes of all non-African populations. The Khoisan peoples, the most famous of which are the Bushmen of the Kalahari, have the largest long term effective populations of any human group. The Yoruba people of Nigeria have a history where they were subject to some population decline, but not to the same extent as non-Africans.

What do we take away from this?

One thing is that we have to consider that the assimilationist model which seems to be necessary for non-Africans, also applies to Africans. For years some geneticists have been arguing that some proportion of African ancestry as well is derived from lineages outside of the main line leading up to anatomically modern humans. Without the smoking gun of ancient genomes this will probably remain a speculative hypothesis. I hope that Lee Berger’s recent assertion that they’ve now dated Homo naledi to ~250,000 years before the present may offer up the possibility that ancient DNA will help resolver the question of African archaic admixture (i.e., if naledi is related to the “ghost population”?).

The second dynamic is that the bottleneck-then-range-expansion which is so important in defining the recent prehistory of non-Africans is not as relevant to Africans during the Pleistocene. The very deep split dates being inferred from whole genome analysis of African populations makes me wonder if multiregional evolution is actually much more important within Africa in the development of modern humans in the last few hundred thousand years. Basically, the deep split dates may highlight that there was recurrent gene flow over hundreds of thousands of years between different closely related hominin populations in Africa.

Ultimately, it doesn’t seem entirely surprising that the “Out of Africa” model does not quite apply within Africa.

Addendum: Over the past ~5,000 years we have seen the massive expansion of agricultural populations within the continent. The “deep structure” therefore may have been erased to a great extent, with Pygmies, Khoisan, and Hadza, being the tip of the iceberg in terms of the genetic variation which had characterized the Africa during the Pleistocene.

April 26, 2017

“Out of Africa” bottleneck is what really matters for mutations

Filed under: Africa,Genetics,Genomics,Human Evolution,Pygmies — Razib Khan @ 10:49 pm


At least in relation to mutational load, if you read a new preprint in biorxiv, The demographic history and mutational load of African hunter-gatherers and farmers:

The distribution of deleterious genetic variation across human populations is a key issue in evolutionary biology and medical genetics. However, the impact of different modes of subsistence on recent changes in population size, patterns of gene flow, and deleterious mutational load remains to be fully characterized. We addressed this question, by generating 300 high-coverage exome sequences from various populations of rainforest hunter-gatherers and neighboring farmers from the western and eastern parts of the central African equatorial rainforest. We show here, by model-based demographic inference, that the effective population size of African populations remained fairly constant until recent millennia, during which the populations of rainforest hunter-gatherers have experienced a ~75% collapse and those of farmers a mild expansion, accompanied by a marked increase in gene flow between them. Despite these contrasting demographic patterns, African populations display limited differences in the estimated distribution of fitness effects of new nonsynonymous mutations, consistent with purifying selection against deleterious alleles of similar efficiency in the different populations. This situation contrasts with that we detect in Europeans, which are subject to weaker purifying selection than African populations. Furthermore, the per-individual mutation load of rainforest hunter-gatherers was found to be similar to that of farmers, under both additive and recessive modes of inheritance. Together, our results indicate that differences in the subsistence patterns and demographic regimes of African populations have not resulted in large differences in mutational burden, and highlight the role of gene flow in reshaping the distribution of deleterious genetic variation across human populations.

There’s two major moving parts in this preprint. First, they using phylogenomic methods to explicitly model population history. Second, they integrated their demographic results in generation and interpreting the distribution of mutations within the exomes of these populations. That is, they combined phylogenomics to gain insight into population genomics, as the latter focuses more on the parameters which define variation with a population.

The data they worked with was from the exome. The regions of the genome which translate into genes. That’s ~30 million bases. They get really good precision due to high coverage, hitting site about 70 times. Their sample was about 300 Africans and 100 Europeans, and they got ~500,000 polymorphisms or variants for their trouble.

The populations were labeled by subsistence and provenance. The Europeans were Belgians. For the Africans they had two groups of hunter-gatherer Pymgies, and two groups of Bantu agriculturalists, sampled from western and eastern locations as you see on the map above.

The admixture plots, which separate out individuals into K numbers of populations break out in a way that makes sense. First, Europeans separate, and the eastern agriculturalist populations have a little bit of evidence of European-like ancestry. This is almost certainly Middle Eastern farmer, which has been found in many East African populations, and those populations which have mixed with them. Then the hunter-gathers separate from the agriculturalists. This is in line with expectation and earlier research; the hunter-gatherers of Africa seem very different from the agriculturalists, and are actually more closely related to each other than the agriculturalists in their neighboring regions.

The exception to this pattern is caused by recent gene flow, which is clearly evident above. Due to population size differences it looks like there is more agricultural ancestry in the Pygmies than vice versa. I wish that they had sampled Mbuti Pygmies. I’m told that this group has the least agricultural admixture.

But then they decided to get fancy and explicitly model demographic histories with fastsimcoal2. What does this do? From the website for the software:

While preserving all the simulation flexibility of simcoal2, fastsimcoal is now implemented under a faster continous-time sequential Markovian coalescent approximation, allowing it to efficiently generate genetic diversity for different types of markers along large genomic regions, for both present or ancient samples. It includes a parameter sampler allowing its integration into Bayesian or likelihood parameter estimation procedure.

fastsimcoal can handle very complex evolutionary scenarios including an arbitrary migration matrix between samples, historical events allowing for population resize, population fusion and fission, admixture events, changes in migration matrix, or changes in population growth rates. The time of sampling can be specified independently for each sample, allowing for serial sampling in the same or in different populations.

The models you see that were tested are pretty simple, and they all seem plausible I suppose. Their simulations suggested that the three above scenarios, with alternative branching patterns and various gene flows, were all of equal likelihood. That is, given the models and the data that they had (4-fold synonymous sites which are likely to be neutral) you can’t distinguish which is right.

In all the models hunter-gatherers diverged relatively recently and so did the agriculturalists. Europeans, who are stand-ins for all non-Africans in this scenario, diverged pretty early from the Africans. But how the Africans relate to each other and Europeans is not totally clear. Why? Because ancient population structure. It is becoming rather obvious now that ~100,000 years ago, and earlier, there were many different modern human lineages which had already diversified. The Khoisan seem to have diverged from other human lineages closer to 200,000 thousand than 100,000 years ago. What this means is that for most of the history of anatomically modern humans population structure  existed between distinct lineages. And some of that persists down to today within Africa.

I’ll bullet point some of their inferences from these models (verbatim quotes below):

  1. Our results suggest that the ancestors of the contemporary RHG, AGR and EUR populations diverged between 85 and 140 thousand years ago (kya), from an ancestral population that underwent demographic expansion between 173 and 191 kya
  2. After the initial population splits, the Ne of AGR and RHG (NaAGR and NaRHG) remained within a range extending from 0.55 to 2.2 times the ancestral African Ne (NHUM), whereas EUR (NaEUR) experienced a decrease in Ne by a factor of three to seven.
  3. The ancestors of the wRHG and eRHG populations diverged 18 to 20 kya (TRHG), and underwent a decreased in Ne by a factor of 3.8 to 5.7 for the wRHG (NwRHG) and 7.1 to 11 for the eRHG (NeRHG), regardless of the branching model considered.
  4. The ancestors of the AGR (NaAGR) split into western and eastern populations 6.7 to 11 kya (TAGR), and underwent a mild expansion, by a factor of 2.3 to 3.1 for the wAGR (NwAGR) and 1.2 to 2.2 for the eAGR (NeAGR).
  5. The EUR population experienced a 7.1- to 8.3-fold expansion (NEUR) 12 to 22 kya (TEUR).

No results are perfect. But some of these dates do not make sense. There’s a lot of circumstantial evidence that the ancestors of European populations began to expand over the last 10,000 years. The dates above suggest there was a Pleistocene expansion. Basically you can divide that value by half, and then you get a reasonable range.

Second, both the agriculturalists sampled here are Bantu speaking, and there’s a good amount of cultural and genetic data for recent shared ancestry of the Bantu over the last 3,000 years. I understand that admixture with a very diverged lineage (e.g., eastern Bantu agriculturalist samples mixing with Nilotic populations, which is how they got some non-African ancestry, as well as local Pygmy groups) can inflate these divergence dates. If that’s the case, they should note that in the text.

We don’t have much historical or archaeological clarity from what I know about divergences between Pygmy groups. This particular group has studied the topic and published on it before, so I’m inclined to trust them more than anyone else. But, the above dates for groups we do know make me a bit more skeptical of a simple divergence around the Last Glacial Maximum.

Then there are the earliest divergences. And 85 to 140,000 year interval is huge for when non-Africans split off from Africans. If closer to 140 than 85, then that means that non-African divergence from Africans preserves ancient African diversity. That is, non-Africans descend from an African group that no longer exists (or has not been sampled in this study at least!). I’ve poked around this question, and when you take into account recent gene flow, it is hard to find the specific African group that non-Africans descend from, though there is some consensus that they branched off from the non-Khoisan Africans later than from the Khoisan.

But there is also a lot of archaeological and some ancient genetic DNA now that indicates that the vast majority of non-African ancestry began to expand rapidly around 50-60,000 years ago. This is tens of thousands of years after the lowest value given above. Therefore, again we have to make recourse to a long period of separation before the expansion. This is not implausible on the face of it, but we could do something else: just assume there’s an artifact with their methods and the inferred date of divergence is too old. That would solve many of the issues.

I really don’t know if the above quibbles have any ramification for the site frequency spectrum of deleterious mutations. My own hunch is that no, it doesn’t impact the qualitative results at all.

Figure 3 clearly shows that Europeans are enriched for weak and moderately deleterious mutations (the last category produces weird results, and I wish they’d talked about this more, but they observe that strong deleterious mutations have issues getting detected). Ne is just the effective population size and s is the selection coefficient (bigger number, stronger selection).

Why are the middle two values enriched? Presumably it’s the non-African bottleneck. This is where another non-African population would have been a nice check to make sure that it was the “Out of Africa” bottleneck…but it’s probably asking a bit much to sequence more individuals to 70x coverage.

The lack of difference between the African populations is an indication that recent demography is not shaping the distribution much. Additionally, they note that gene flow between the African groups probably increased diversity in some ways, so that as long as a group is connected with other populations it will probably be rescued (note that none of these in their data were particular inbred as judging by runs of homozygosity).

Finally, they found that the number of homozygote mutations that were deleterious is higher in their model results for Europeans than the African groups. This is not surprising, and what one expects. But, they found that this is a function likely of continuous gene flow between the African groups. Without gene flow homozygosity would have been much higher. This gets back to the fact that gene flow is a powerful homogenizing tool, and the lack of gene flow has to be pretty extreme for divergence to occur.

Which brings us back to the “Out of Africa” event. The next ten years are going to see a lot of investigation of African phyologenomics and population genomics. Basically, the relationships, and selection pressures. It is totally implausible that Bantu groups in Kenya and Tanzania did not absorb local non-Nilotic populations. We’ll figure that out. Additionally, selection pressures are probably different between different groups. We’ll know more about that. But, ancient DNA will probably give us some understanding of why non-Africans went through such a massive demographic sieve. We know in broad sketches. But most people want to fill in the details.

Citation: The demographic history and mutational load of African hunter-gatherers and farmers, Marie Lopez, Athanasios Kousathanas, Helene Quach, Christine Harmant, Patrick Mouguiama-Daouda, Jean-Marie Hombert, Alain Froment, George H Perry, Luis B Barreiro, Paul Verdu, Etienne Patin, Lluis Quintana-Murci, doi: https://doi.org/10.1101/131219

April 23, 2017

The logic of human destiny was inevitable 1 million years ago

Filed under: Evolution,Genetics,Genomics,Human Evolution,Human Genetics — Razib Khan @ 1:11 pm

Robert Wright’s best book, Nonzero: The Logic of Human Destiny, was published near 20 years ago. At the time I was moderately skeptical of his thesis. It was too teleological for my tastes. And, it does pander to a bias in human psychology whereby we look to find meaning in the universe.

But this is 2017, and I have somewhat different views.

In the year 2000 I broadly accepted the thesis outlined a few years later in The Dawn of Human Culture. That our species, our humanity, evolved and emerged in rapid sequence, likely due to biological changes of a radical kind, ~50,000 years ago. This is the thesis of the “great leap forward” of behavioral modernity.

Today I have come closer to models proposed by Michael Tomasello in The Cultural Origins of Human Cognition and Terrence Deacon in The Symbolic Species: The Co-evolution of Language and the Brain. Rather than a punctuated event, an instance in geological time, humanity as we understand it was a gradual process, driven by general dynamics and evolutionary feedback loops.

The conceit at the heart of Robert J. Sawyer’s often overly preachy Neanderthal Parallax series, that if our own lineage went extinct but theirs did not they would have created a technological civilization, is I think in the main correct. It may not be entirely coincidental that the hyper-drive cultural flexibility of African modern humans evolved in African modern humans first. There may have been sufficient biological differences to enable this to be likely. But I believe that if African modern humans were removed from the picture Neanderthals would have “caught up” and been positioned to begin the trajectory we find ourselves in during the current Holocene inter-glacial.

Luke Jostins’ figure showing across board encephalization

The data indicate that all human lineages were subject to increased encephalization. That process trailed off ~200,000 years ago, but it illustrates the general evolutionary pressures, ratchets, or evolutionary “logic”, that applied to all of them. Overall there were some general trends in the hominin lineage that began to characterized us about a million years ago. We pushed into new territory. Our rate of cultural change seems to gradually increased across our whole range.

One of the major holy grails I see now and then in human evolutionary genetics is to find “the gene that made us human.” The scramble is definitely on now that more and more whole genome sequences from ancient hominins are coming online. But I don’t think there will be such gene ever found. There isn’t “a gene,” but a broad set of genes which were gradually selected upon in the process of making us human.

In the lingo, it wasn’t just a hard sweep from a de novo mutation. It was as much, or even more, soft sweeps from standing variation.

April 20, 2017

Aryan marauders from the steppe came to India, yes they did!

Filed under: Genetics,Genomics,History,India — Razib Khan @ 10:21 pm

Its seems every post on Indian genetics elicits dissents from loquacious commenters who are woolly on the details of the science, but convinced in their opinions (yes, they operate through uncertainty and obfuscation in their rhetoric, but you know where the axe is lodged). This post is an attempt to answer some questions so I don’t have to address this in the near future, as ancient DNA papers will finally start to come out soon, I hope (at least earlier than Winds of Winter).

In 2001’s The Eurasian Heartland: A continental perspective on Y-chromosome diversity Wells et al. wrote:

The current distribution of the M17 haplotype is likely to represent traces of an ancient population migration originating in southern Russia/Ukraine, where M17 is found at high frequency (>50%). It is possible that the domestication of the horse in this region around 3,000 B.C. may have driven the migration (27). The distribution and age of M17 in Europe (17) and Central/Southern Asia is consistent with the inferred movements of these people, who left a clear pattern of archaeological remains known as the Kurgan culture, and are thought to have spoken an early Indo-European language (27, 28, 29). The decrease in frequency eastward across Siberia to the Altai-Sayan mountains (represented by the Tuvinian population) and Mongolia, and southward into India, overlaps exactly with the inferred migrations of the Indo-Iranians during the period 3,000 to 1,000 B.C. (27). It is worth noting that the Indo-European-speaking Sourashtrans, a population from Tamil Nadu in southern India, have a much higher frequency of M17 than their Dravidian-speaking neighbors, the Yadhavas and Kallars (39% vs. 13% and 4%, respectively), adding to the evidence that M17 is a diagnostic Indo-Iranian marker. The exceptionally high frequencies of this marker in the Kyrgyz, Tajik/Khojant, and Ishkashim populations are likely to be due to drift, as these populations are less diverse, and are characterized by relatively small numbers of individuals living in isolated mountain valleys.

In a 2002 interview with the India site Rediff, the first author was more explicit:

Some people say Aryans are the original inhabitants of India. What is your view on this theory?

The Aryans came from outside India. We actually have genetic evidence for that. Very clear genetic evidence from a marker that arose on the southern steppes of Russia and the Ukraine around 5,000 to 10,000 years ago. And it subsequently spread to the east and south through Central Asia reaching India. It is on the higher frequency in the Indo-European speakers, the people who claim they are descendants of the Aryans, the Hindi speakers, the Bengalis, the other groups. Then it is at a lower frequency in the Dravidians. But there is clear evidence that there was a heavy migration from the steppes down towards India.

But some people claim that the Aryans were the original inhabitants of India. What do you have to say about this?

I don’t agree with them. The Aryans came later, after the Dravidians.

Over the past few years I’ve gotten to know the above first author Spencer Wells as a personal friend, and I think he would be OK with me relaying that to some extent he was under strong pressure to downplay these conclusions. Not only were, and are, these views not popular in India, but the idea of mass migration was in bad odor in much of the academy during this period. Additionally, there was later work which was less clear, and perhaps supported an Indian origin for R1a1a. Spencer himself told me that it was not impossible for R1a to have originated in India, but a branch eventually back-migrated to southern Asia.

But even researchers from the group at Stanford where he had done his postdoc did not support this model by the middle 2000s, Polarity and Temporality of High-Resolution Y-Chromosome Distributions in India Identify Both Indigenous and Exogenous Expansions and Reveal Minor Genetic Influence of Central Asian Pastoralists. In 2009 a paper out of an Indian group was even stronger in its conclusion for a South Asian origin of R1a1a, The Indian origin of paternal haplogroup R1a1* substantiates the autochthonous origin of Brahmins and the caste system.

By 2009 one might have admitted that perhaps Spencer was wrong. I was certainly open to that possibility. There was very persuasive evidence that the mtDNA lineages of South Asia had little to do with Europe or the Middle East.

Yet a closer look at the above papers reveals two major systematic problems.

First, ancient DNA has made it clear that there has been major population turnover during the Holocene, but this was not the null hypothesis in the 2000s. Looking at extant distributions of lineages can give one a distorted view of the past. Frankly, the 2009 Indian paper was egregious in this way because they included Turkic groups in their Central Asian data set. Even in 2009 there was a whole lot of evidence that Central Asian Turkic groups were likely very different from Indo-European Turanian populations which would have been the putative ancestors of Indo-Aryans. Honestly the authors either consciously loaded the die to reduce the evidence for gene flow from Central Asia, or they were ignorant (the nature of the samples is much clearer in the supplements than the  primary text for what it’s worth).

Second, Y chromosomal marker sets in the 2000s were constrained to fast mutating microsatellite regions or less than 100 variant SNPs on the Y. Because it is so repetitive the Y chromosome is hard to sequence, and it really took the technologies of the last ten years to get it done. Both the above papers estimate the coalescence of extant R1a1a lineages to be 10-15,000 years before the present. In particular, they suggest that European and South Asian lineages date back to this period, pushing back any possible connection between the groups, and making it possible that European R1a1a descended from a South Asian founder group which was expanding after the retreat of the ice sheets. The conclusions were not unreasonable based on the methods they had.  But now we have better methods.*

Whole genome sequencing of the Y, as well as ancient DNA, seems to falsify the above dates. Though microsatellites are good for very coarse grain phyolgenetic inferences, one has to be very careful about them when looking at more fine grain population relationships (they are still useful in forensics to cheaply differentiate between individuals, since they accumulate variation very quickly). They mutate fast, and their clock may be erratic.

Additionally, diversity estimates were based on a subset of SNP that were clearly not robust. R1a1a is not diverse anywhere, though basal lineages seem to be present in ancient DNA on the Pontic steppe in some cases.

To show how lacking in diversity R1a1a is, here are the results of a 2016 paper which performed whole genome sequencing on the Y. Instead of relying on the order of 10 to 100 SNPs, this paper discover over 65,000 Y variants worldwide. Notice how little difference there is between different South Asian groups below, indicative of a massive population expansion relatively recently in time which didn’t even have time to exhibit regional population variation. They note that “The most striking are expansions within R1a-Z93 [the South Asian clade], ~4.0–4.5 kya. This time predates by a few centuries the collapse of the Indus Valley Civilization, associated by some with the historical migration of Indo-European speakers from the western steppes into the Indian sub-continent.

(BEB = Bengali, GIH = Gujarati, PJL = Punjabi, STU = Sri Lanka Tamil, ITU = Indian Telugu)

The spatial distribution of Z93 lineages of R1a is as you can see to the left. There are branches in South Asia, Central Asia, and in the Altai region. Ancient DNA from the Bronze Age Mongolia has found Z93. Modern Mongolians clearly have a small, but appreciable, fraction of West Eurasian ancestry. Some also carry R1a1a. Z93 has also been found in North-Central Asian steppe samples that date to ~4,500 years before the present.

Today with ancient DNA we’re discovering individuals who lived around the time of the massive  expansion alluded to above. What are these individuals like? They are a mix of European, Central Eurasian, Near Eastern, and Siberian. Many of them share quite a bit of ancestry with South Asian populations, in particular those from the northwest of subcontinent, as well as upper castes more generally.

A new paper using ancient DNA from Scythians (Iranian speakers) also shows that they carried Z93. Some of them had East Asian admixture. These were the ones from the eastern steppe. So not entirely surprising. In the supplements of the paper they have an admixture plot with many populations. At K = 15 in supplementary figure 14 you see many ancient Central Eurasian populations run against modern groups. At this K there is a South Asian modal cluster which is found in South Asians as well as nearby Iranian groups from Afghanistan.

It is not light green or dark blue. You see see that this salmon color is modal in tribal South Indian populations, or non-Brahmin South Indians. It drops in frequency as you move north and west, and as you move up the caste ladder. Observe that is present even among the relatively isolated Kalash people of Chitral.

Outside of South Asia-Afghanistan, this salmon component is found among Thai and Cambodians. From talking to various researchers, and recent published findings, it seems clear that this signature is not spurious, but is indicative of some migration from South Asia to Southeast Asia in the historical period, as one might infer based on cultural affinities. It is also found at lower frequencies among the Uyghur of Xinjiang. This is not entirely surprising either. This region of the Tarim basin was connected to Kashmir across the Pamirs. The 4th century Buddhist monk from the Tarim basin city of Kucha, who was instrumental in the translation of texts into Chinese, Kumārajīva, may have had a Kashmiri father.

Even before Islam much of Northwest India and Central Asia were under the rule of the same polity, and after Islam there is extensive record of the enslavement of many Indians in the cities of the eastern Islamic world, as well as the travel of some Indian merchants and intellectuals into these regions.

And yet this South Asia cluster is not present in the ancient steppe samples carrying R1a1a-Z93. None of them to my knowledge. Many ancient samples share ancestry with South Asians. For example it seems that many ancient West Asian samples from Iran share common history as evident in genetic drift patterns with many South Asians. And, there is good evidence that a subset of South Asians, skewed toward northwest and upper caste groups, share drift with steppe Yamna samples. But South Asians are often clearly composites of these exogenous populations and an indigenous component with affinities with Andaman Islanders, and more distantly Southeast Asians and other eastern non-Africans.

How can you reconcile this with migration out of South Asia? The path is found in publications such as Genetic Evidence for Recent Population Mixture in India. Here you have a paper which models mixing between Ancestral North Indians (ANI) and Ancestral South Indians (ASI). The ANI would be the source population for the ancestry shared with West Eurasians. And, they would lack ASI ancestry because the mixing had not occurred. The admixture dates the paper are between two and four thousand years before the present.

There is a problem though. These methods detect the last admixture events. Therefore, they are a lower bound on major mixing events, not a record of when there was no mixing. Secondarily, but not less importantly, recent work indicates that because of the pulse admixture simplification these methods likely underestimate the time period of admixture.

Another issue for me is the idea that ANI and ASI could be so separate within India. If ANI is the source of gene flow into other parts of Eurasia from South Asia, then I believe that ASI is intrusive to the subcontinent. I don’t think that ASI being intrusive is so implausible. Southeast Asia has undergone massive genetic changes over the Holocene, and it may be that there was much more ASI ancestry in placers like Burma before the arrival of Austro-Asiatic rice farmers. The presence of Austro-Asiatic languages in northeast India and central India shows a precedent of migration from Southeast Asia into the subcontinent.

In sum, the balance of evidence suggests male mediated migration into South Asia from Central Asia on the order of ~4-5,000 years ago. There are lots of details to be worked out, and this is not an assured model in terms of data, but it is the most likely. In the near future ancient DNA will clear up confusions. Writing very long but confused comments just won’t change this state of affairs. New data will.

Addendum: Indian populations have finally been relatively well sampled, thanks to Mait Mepsalu’s group in Estonia, David Reich’s lab and, the Indian collaborators of both, and the 1000 Genomes (HGDP gave us Pakistanis). Additionally, Zack Ajmal’s Harappa website did some work filling in some holes in the early 2010s.

* A Facebook argument broke out about one of my posts where one interlocutor asserted that he leaned on papers from the late 2000s, not all the new stuff. That’s obviously because the new stuff did not support his preferred position, while the old stuff did. I would prefer that faster-than-light travel were possible, so I’ll just stick to physics before 1910?

Oxford Nanopore finally giving hope to biologist’s dreams

Filed under: Genomics,Oxford Nanopore,Sequencing — Razib Khan @ 5:48 pm

I don’t talk too much about genomic technology because it changes so fast. Being up-to-date on the latest machines and tools often requires regular deep-dives right now, though I believe at some point technological improvements will plateau as the data returned will be cheap and high quality enough that there won’t be much to gain on the margin.

Of course we’ve already come a long way. Fifteen years ago a “whole human genome” cost on the order of billions of dollars. Today a high quality whole human genome will run you on the order of $1,000. This is fundamentally a technology driven change, with big metal machines automatically generating reads and powerful computers to process them. One couldn’t imagine such a scenario 30 years ago because the technology wasn’t there.

I’ve stated before that I don’t think genomics fundamentally alters what we know and understand about evolution. At least so far. But it is a huge change in the domain of medicine. Cleary the human genomicists, especially Francis Collins, overhyped the yield of the technology in relation to healthcare in the 2000s. But with cheap and ubiquitous sequencing we may see the end of Mendelian diseases in our lifetime (through screening and possibly at some point CRISPR therapy).

This has been driven by technological innovation in the private sector around a few firms. The famous chart showing the massive decline in the cost of genomic sequencing over the past 15 years is due in large part to the successes of Illumina. But, Illumina has also had a quasi-monopoly on the field over the past five years (or more), and that shows with the leveling off of the decline in cost. Until the past year….

What gives? Many people believe that Illumina is moving again in part because a genuine challenger is emerging, or at least the flicker of a challenge, in the form of Oxford Nanopore. Oxford Nanopore has been around since 2005, but it really came into the public eye around 2010 or so. But like many tech companies it overpromised in the early years. I remember skeptically listening to a friend in the fall of 2011 talk about how quickly Nanopore was going to change the game…. I didn’t put too much stock into these sorts of presentations to hopeful researchers because I remember Pacific Biosciences making the same sort of pitch to amazed biologists in 2008. Pac Bio is still around, but has turned out to be a bit player, rather than a challenger to Illumina.

But I have to admit that Nanopore has really started to step up its game of late. Probably one of the major things it has accomplished is that it’s made us reimagine what sequencing technology should look like. Rather than refrigerators of various sizes, Oxford Nanopore allows us to imagine sequencing technology which exhibits a form factor more analogous to a USB thumb drive. The first time I saw a Nanopore machine in the flesh I knew intellectually what I was going to see…but because of my deep intuitions I still overlooked the two Nanopore machines laying on the workbench in front of me.

Despite their amazing form factor, these early Nanopore machines had limited application. They didn’t generate much data, and so were utilized by researchers who worked with smaller genomes. Scientists who worked with bacteria seem to have been using them a lot, for example. Additionally the machines were error prone and people were working out their kinks in real time in laboratories (one tech told me early on they were so small that he swore they were affected by ambient vibrations so he found ways to dampen that source of error).

A new preprint suggests we may be turning the corner though, Nanopore sequencing and assembly of a human genome with ultra-long reads:

Nanopore sequencing is a promising technique for genome sequencing due to its portability, ability to sequence long reads from single molecules, and to simultaneously assay DNA methylation. However until recently nanopore sequencing has been mainly applied to small genomes, due to the limited output attainable. We present nanopore sequencing and assembly of the GM12878 Utah/Ceph human reference genome generated using the Oxford Nanopore MinION and R9.4 version chemistry. We generated 91.2 Gb of sequence data (~30x theoretical coverage) from 39 flowcells. De novo assembly yielded a highly complete and contiguous assembly (NG50 ~3Mb). We observed considerable variability in homopolymeric tract resolution between different basecallers. The data permitted sensitive detection of both large structural variants and epigenetic modifications. Further we developed a new approach exploiting the long-read capability of this system and found that adding an additional 5x-coverage of “ultra-long” reads (read N50 of 99.7kb) more than doubled the assembly contiguity. Modelling the repeat structure of the human genome predicts extraordinarily contiguous assemblies may be possible using nanopore reads alone. Portable de novo sequencing of human genomes may be important for rapid point-of-care diagnosis of rare genetic diseases and cancer, and monitoring of cancer progression. The complete dataset including raw signal is available as an Amazon Web Services Open Dataset at: https://github.com/nanopore-wgs-consortium/NA12878.

30x just means that you’re getting bases sampled typically 30 times, so that you have a very accurate and precise read on its state. 30x has become the default standard in medical genomics. If Nanopore can do 30x on human genomes at reasonable cost it won’t be a niche player much longer.

The read length is important because last I checked the human genome still had large holes in it. The typical Illumina machine produces average read lengths in the low hundreds of base pairs. If you have large repetitive regions of the human genome (and you do have these), you’re never going to span them with such short yardsticks. Additionally, these short reads have to be tiled together when you assemble a genome from raw results, and this is a computationally really intensive task. It’s good when you have a reference genome you can align to as a scaffold. But researchers who don’t work on humans or model organisms may not have a good reference genome, or in many cases a reference genome at all.

Pac Bio occupies a space where it provide really long reads for a high price point. Most of the time this isn’t necessary, but imagine you work on a disease which is caused by large repetitive regions. You are likely willing to pay the price that is asked. And because Pac Bio generates very long reads it makes de novo assembly much easier, as your algorithm has to tile together far fewer contiguous sequences, and long sequences are less likely to have lots of repetitive matches in the genome.

But Pac Bio machines are expensive and huge. In the abstract above it alludes to “Portable de novo sequencing of human genomes.” This is a huge deal. The dream, as whispered by some genomicists I have known, is that at a point in the future biologists would carry portable sequencers which would produce very long reads that so that they could de novo assemble sequences on the spot. A concrete example might be a health inspector checking on the sorts of microbes found on the counter of a restaurant, or a field ecologist who might be sample various fungi to discover cryptic species.

Obviously this is still a dream. The preprint above makes it clear that to do what they did required a lot of novel techniques and development of new tools. This isn’t beta technology, it’s early alpha. But because it’s 2017 the outlines of the dream are coming into public view.

Citation: Nanopore sequencing and assembly of a human genome with ultra-long reads
Miten Jain, Sergey Koren, Josh Quick, Arthur C Rand, Thomas A Sasani, John R Tyson, Andrew D Beggs, Alexander T Dilthey, Ian T Fiddes, Sunir Malla, Hannah Marriott, Karen H Miga, Tom Nieto, Justin O’Grady, Hugh E Olsen, Brent S Pedersen, Arang Rhie, Hollian Richardson, Aaron Quinlan, Terrance P Snutch, Louise Tee, Benedict Paten, Adam M. Phillippy, Jared T Simpson, Nicholas James Loman, Matthew Loose
bioRxiv 128835; doi: https://doi.org/10.1101/128835

April 19, 2017

Mouse fidelity comes down to the genes

Filed under: Genetics,Genomics,Human Genetics — Razib Khan @ 10:02 pm

While birds tend to be at least nominally monogamous, this is not the case with mammals. This strikes some people as strange because humans seem to be monogamous, at least socially, and often we take ourselves to be typically mammalian. But of course we’re not. Like many primates we’re visual creatures, rather than relying in smell and hearing. Obviously we’re also bipedal, which is not typical for mammals. And, our sociality scales up to massive agglomerations of individuals.

How monogamous we are is up for debate. Desmond Morris, who is well known to many from his roles in television documentaries, has been a major promoter of the idea that humans are monogamous, with a focus on pair-bonds. In contrast, other researchers have highlighted our polygamous tendencies. In The Mating Mind Geoffrey Miller argues for polygamy, and suggests that pair-bonds in a pre-modern environment were often temporary, rather than lifetime (Miller is now writing a book on polyamory).

The fact that in many societies high status males seem to engage in polygamy, despite monogamy being more common, is one phenomenon which confounds attempts to quickly generalize about the disposition of our species. What is preferred may not always be what is practiced, and the external social adherence to norms may be quite violated in private.

Adducing behavior is simpler in many other organisms, because their range of behavior is more delimited. When it comes to studying mating patterns in mammals voles have long been of interest as a model. There are vole species which are monogamous, and others which are not. Comparing the diverged lineages could presumably give insight as to the evolutionary genetic pathways relevant to the differences.

But North American deer mice, Peromyscus, may turn to be an even better bet: there are two lineages which exhibit different mating patterns which are phylogenetically close enough to the point where they can interbreed. That is crucial, because it allows one to generate crosses and see how the characteristics distribute themselves across subsequent generations. Basically, it allows for genetic analysis.

And that’s what a new paper in Nature does, The genetic basis of parental care evolution in monogamous mice. In figure 3 you can see the distribution of behaviors in parental generations, F1 hybrids, and the F2, which is a cross of F1 individuals. The widespread distribution of F2 individuals is likely indicative of a polygenic architecture of the traits. Additionally, they found that some traits are correlated with each other in the F2 generation (probably due to pleiotropy, the same gene having multiple effects), while others were independent.

With the F2 generation they ran a genetic analysis which looked for associations between traits and regions of the genome. They found 12 quantitative trait loci (QTLs), basically zones of the genome associated with variation on one or more of the six traits. From this analysis they immediately realized there was sexual dimorphism in terms of the genetic architecture; the same locus might have a different effect in the opposite sex. This is evolutionarily interesting.

Because the QTLs are rather large in terms of physical genomic units the authors looked to see which were plausible candidates in terms of function. One of their hits was vasopressin, which should be familiar to many from vole work, as well as some human studies. Though the QTL work as well as their pup-switching experiment (which I did not describe) is persuasive, the fact that a gene you’d expect shows up as a candidate really makes it an open and shut case.

The extent of the variation explained by any given QTL seems modest. In the extended figures you can see it’s mostly in the 1 to 5 percent range. In Carl Zimmer’s excellent write up he ends:

But Dr. Bendesky cautioned that the vasopressin gene would probably turn out to be just one of many that influence oldfield mice. Though it is strongly linked to parental behavior, the vasopressin gene accounts for 6.7 percent of the variation in nest building among males, and only 2.9 percent among females.

The genetic landscape of human parenting will turn out to be even more rugged, Dr. Bendesky predicted.

“You cannot do a 23andMe test and find out if your partner is going to be a good father,” he said.

Sort of. The genetic architecture above is polygenic…but not incredibly diffuse. The proportion of variation explained by the largest effect allele is more than for height, and far more than for education. If human research follows up on this, I wouldn’t be surprised if you could develop a polygenic risk score.

But I don’t have a good intuition on how much variation in humans there really is for these sorts of traits that are heritable. I assume some. But I don’t know how much. And how much of the variance in behavior might be explained by human QTLs? Humans don’t lick or build nests, or retrieve pups. Also, as one knows from Genetics and Analysis of Quantitative Traits sexually dimorphic traits take a long time to evolve. These are two deer mice species. Within humans there may not have been enough time for this sort of heritable complexity of behavior to evolve.

There are a lot of philosophical issues here about translating to a human context.

Nevertheless, this research shows that ingenious animal models can powerfully elucidate the biological basis of behavior.

Citation: The genetic basis of parental care evolution in monogamous mice. Nature (2017) doi:10.1038/nature22074

April 15, 2017

Genetic variation in human populations and individuals

Filed under: Genetics,Genomics,Human Genetics,Polymorphisms,SNPs — Razib Khan @ 9:25 pm


I’m old enough to remember when we didn’t have a good sense of how many genes humans had. I vaguely recall numbers around 100,000 at first, which in hindsight seems rather like a round and large number. A guess. Then it went to 40,000 in the early 2000s and then further until it converged to some number just below 20,000.

But perhaps more fascinating is that we have a much better catalog of the variation across the whole human genome now. Often friends ask me questions of the form: “so DTC genomic company X has about 800,000 SNPs, is that enough to do much?” To answer such a question you need some basic numbers in your head, as well as what you want to “do.”

First, the human genome has about 3 billion base pairs (3 Gb). That’s a lot. But most of the genome famously doesn’t code for proteins. The exome, the proportion of the genome where bases directly translate into a protein accounts for 1% of the whole genome. That’s 30 million bases (30 Mb). But this small region of the genome is very important, as the vast majority of major disease mutations are found in the exome.

When it comes to a standard 800K SNP chip, which samples 800,000 positions across the 3 Gb genome, it is likely that the designers enriched the marker set for functional positions relevant to diseases. Not all marker positions are created equal. Though even outside of those functional positions there are often nearby SNPs that can “tag” them, so you can infer one from the state of the other.

But are 800,000 positions enough to make good ancestry inference? (to give one example) Yes. 800,000 is actually a substantial proportion of the polymorphism in any given genome. There have been some papers which improved on the numbers in 2015’s A global reference for human genetic variation, but it’s still a good comprehensive review to get an order-of-magnitude sense. The table below gives you a sense of individual variation:

Median autosomal variant sites per genome

When it comes to single nucleotide polymorphisms (SNPs), what SNP chips are getting at, an 800K array should get a substantial proportion of your genome-wide variation. More than enough for ancestry inference or forensics. The singleton column shows mutations specific to the individual.  When focusing on new mutations specific to an individual that might cause disease, singleton large deletions and nonsynonymous SNPs is really where I’d look.

But what about whole populations? The plot to the left shows the count of variants as a function of alternative allele frequency. When we say “SNP”, you really mean variants which exhibit polymorphism at a particular cut-off frequency for the minor allele (often 1%). It is clear that as the minor allele frequency increases in relation to the human reference genome the number of variants decreases.

From the paper:

The majority of variants in the data set are rare: ~64 million autosomal variants have a frequency <0.5%, ~12 million have a frequency between 0.5% and 5%, and only ~8 million have a frequency >5% (Extended Data Fig. 3a). Nevertheless, the majority of variants observed in a single genome are common: just 40,000 to 200,000 of the variants in a typical genome (1–4%) have a frequency <0.5% (Fig. 1c and Extended Data Fig. 3b). As such, we estimate that improved rare variant discovery by deep sequencing our entire sample would at least double the total number of variants in our sample but increase the number of variants in a typical genome by only ~20,000 to 60,000.

An 800K SNP chip will be biased toward the 8 million or so variants with a frequency of 5%. This number gives you a sense of the limited scope of variation in the human genome. 0.27% of the genome captures a lot of the polymorphism.

Citation: 1000 Genomes Project Consortium. “A global reference for human genetic variation.” Nature 526.7571 (2015): 68-74.

April 7, 2017

Why humans have so many pulse admixtures

Filed under: Admixture,Evolution,Genetics,Genomics — Razib Khan @ 5:38 pm

The Blank Slate is one of my favorite books (though I’d say The Language Instinct is unjustly overshadowed by it). There is obviously a substantial biological basis in human behavior which is mediated by genetics. When The Blank Slate came out in the early 2000s one could envisage a situation in 2017 when empirically informed realism dominated the intellectual landscape. But that was not to be. In many ways, for example in sex differences, we’ve gone backward, while there is still undue overemphasis in our society on the environmental impact parents have on children (as opposed to society more broadly).

But genes do not determine everything, obviously. Several years after reading The Blank Slate I read Not by Genes Alone: How Culture Transformed Human Evolution. In this work Peter Richerson and Robert Boyd outline their decades long project of modeling cultural variation and evolution formally in a manner reminiscent of biological evolution. Richerson and Boyd’s program does not start from a “blank slate” assumption. Rather, it is focused on broad macro-social dynamics where cultural variation “swamps” out biological variation.

Recall that in classic population genetic theory a major problem with group level selection is that gene flow between adjacent groups quickly removes between group variation. One migrant between two groups per generation is enough for them not to diverge genetically. For group selection to occur the selective effect has to be very strong or the between group difference has to be very high. Rather than talking about genetics though, where the debate is still live, and the majority consensus is still that biological group selection is not that common (depending on how you define it), let’s talk about human culture.

Here the group level differences are extreme and the boundaries can be sharp. Historically it seems likely that most groups which were adjacent to each other looked rather similar because of gene flow and similar selective pressures. Even though in medieval Spain there was a generality, probably true, that Muslims were swarthier than Christians*, there was a palpable danger in battle of identifying friend from foe because the two groups overlapped too much in appearance.

This brings up how one might delineate differences culturally. In battle opposing armies wear distinct uniforms and colors so that the distinction can be made. But obviously one change uniform surreptitiously (perhaps taking the garb from the enemy dead). This is why physical adornment such as tattoos are useful, as they are “hard to fake.” Perhaps the most clear illustration of this dynamic is the Biblical story for the origin of the term shibboleth. Even slight differences in accent are clear to all, and, often difficult to mimic once in adulthood.

Biological evolution mediated through genes is relatively slow and constrained compared to cultural evolution. Whole regions of central and northern Europe shifted from adherence to Roman Catholicism to forms of Protestantism on the order of 10 years. Of course religion is an aspect of culture where change can happen very rapidly, but even language shifts can occur in only a few generations (e.g., the decline of regional German and Italian dialects in the face of standard forms of the language).

Cultural evolution as a formally modeled neofunctionalism is credibly outlined in works such as Peter Turchin’s Ultrasociety: How 10,000 Years of War Made Humans the Greatest Cooperators on Earth. That’s not what I want to focus on here. Rather, I contend that the reality of massive pulse admixtures evident in the human genome over the past 10,000 years, at minimum, is a function of the fact that human cultural evolutionary processes result in winner-take-all genetic consequences.

A concrete example of what I’m talking about would compare the peoples of the Italian peninsula and the Iberian peninsula around 1500. The two populations are not that different genetically, and up to that point shared many cultural traits (and continue to do so). But, a combination of geography and history resulted in Iberian demographic expansion in the several hundred years after 1500, whereby today there are probably many more descendants of Iberians than Italians. This is not a function of any deep genetic difference between the two groups. There aren’t deep genetic differences in fact. Rather, the social and demographic forces which propelled Iberia to imperial status redounded upon the demographic production of Iberians in the future. In addition, the New World underwent a massive pulse admixture between Iberians, and native Amerindians, as well as Africans, usually brought over as slaves, due the cultural and political history of the period.

The pulse admixture question is rather interesting academically. To some extent current methods are biased toward detection of pulse admixtures, and even fit continuous gene flow as pulse admixtures. A quick rapid exchange of gene flow and then recombination breaking apart associations of markers which are ancestrally informative haplotypes is something you can test for. But I think we can agree that the gene flow triggered by the Columbian Exchange was a pulse admixture, and there’s too much concurrent evidence from uniparental lineage turnover in the ancient DNA to dismiss the non-historically corroborated signatures of pulses as simply artifacts.

Nevertheless continuous gene flow does occur. That is, normal exchange of individuals between neighboring demes as a slow simmer over time. But the idea that we are a clinal ring species or something like that isn’t right in my opinion. Part of the story are strong geographical barriers. But another major part is that cultural revolutions and advantages introduce huge short-term demographic advantages to particular groups, and the shake out of inter-group competition can be dramatic.

Therefore, I make a prediction: the more cultural evolutionary dynamics a species is subject to, the more pulse admixture you’ll be able to detect. For example, pulse admixture should be more important in social insects than their solitary relatives.

* Not only was some of the ancestry of Muslims North African, Muslim rule was longest in the southern and southeastern regions, where people were not as fair as in the north.

Older Posts »

Powered by WordPress