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

March 14, 2019

The Ubiquitous Sequencing Age

Filed under: Genomics — Razib Khan @ 10:46 pm

Several years ago Yaniv Ehrlich published A Vision for Ubiquitous Sequencing. We’re inching in that direction. In The Atlantic Sarah Zhang has a piece, An Abandoned Baby’s DNA Condemns His Mother, while The New York Times just came out with, Old Rape Kits Finally Got Tested. 64 Attackers Were Convicted:

Still, even with such successes, the problem of untested rape kits persists. Advocates for rape victims estimate that about 250,000 kits remain untested across the country.

Unfortunately, until recently, the ‘forensic genetics’ employed rather primitive 1990s technology. But that’s changing, though both money and expertise need to be brought to bear. Companies such as Gencove and Othram are bringing that expertise to a broader market, with the latter company focusing specifically on the forensic market.

So ubiquitous sequencing is happening. Soon. What does that mean? We need to think about privacy. We need to think about data. We need to reflect on the broader implications of this world beyond specific targeted tasks such as forensic identification.

February 6, 2019

Dreaming of billions of genomes

Filed under: Genetics,Genomics,Privacy — Razib Khan @ 8:43 pm

In the year 2000 scientists finished the draft of the complete human genome. The “reference” for what came after. Even ten years earlier some researchers were questioning the feasibility of any such project! In the early 1990s, many assumed it would be many decades before the first human genome was mapped. What changed?

Technology invaded science. The first human sequence cost three billion dollars. Today one can be had for $1,000. In other words, a genome was three million times more expensive just 20 years ago.

An Illumina sequencer

Instead of the laborious process of tracing inheritance patterns through visible markers, modern genomics utilizes the molecular nature of DNA to enable automation and computation to “read” the full sequence. In less than 20 years we’ve gone from a single human genome sequence to hundreds of thousands of whole genome sequences, and tens of millions of samples which have undergone high-density genotyping using “SNP-array” technology.

Though the human genome is three billion bases, only a small proportion of it codes for genes, and an even smaller proportion holds any variation of interest in a population genetic sense. The millions of genotypes in the databases of private consumer genomic firms may only capture a small number of genetic positions, between 100,000 and one million, but this small number is enough to draw many important conclusions. In particular, what common diseases you are at risk for, and what part of the world your family is likely from, and who your relatives are.

In other words, probably 90% of the things you would want to know about your genetics can be inferred from 0.03% of your whole genome! Today private companies are sitting atop a pot of potential gold because the genome doesn’t change over your lifetime. It is only an appreciating asset as time progresses, as more research unveils details of mechanism and associations.

You are being watched!

Within twenty to thirty years it is likely that a billion human genomes will be sequenced. The field will have fully transitioned from basic science to information technology. And as with any information technology, privacy and data sharing will be important things to consider. It is likely that some governments, like that of China, will have total access to their citizens’ data, while others, such as those of the European Union, will limit access.

But even without top-down invasion of privacy, the proliferation of databases and sequences will mean that one’s genetic information will be shared like credit scores across vendors. And just like with credit scores and histories, there will be data breaches. And while credit scores as ephemeral, your sequence is permanent.

Total strangers may have access to your disease risks, your relatives, and your heritage. Things today which is guarded privately may become totally transparent to anyone who wants to look unless precautions are taken.

The decisions we make today will have consequences for future generations. This applies to individuals, corporations, and the government.

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

Dreaming of billions of genomes was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

January 16, 2019

To understand Neanderthals we need to understand ourselves

Filed under: Evolution,Genetics,Genomics,Neanderthals — Razib Khan @ 1:56 pm

In 2010 researchers sequenced the whole genome of a single Neanderthal. From comparing this genome to that of humans alive today they concluded, to their surprise, that many modern human populations had Neanderthal ancestry! More specifically, all populations outside of Africa seem to have some Neanderthal ancestry.

Over the last decade, researchers have come to agree that this finding is a true one. That is, modern humans do have Neanderthal ancestry. In fact, most scientists now believe that there is also ancestry from a third human population, Denisovans, across eastern Eurasia and Oceania.

But there is more to the story than we understood in 2010. Then, researchers argued there was a single admixture as humans left Africa. Today, some researchers contend there were multiple Neanderthal admixtures, with East Asians having more Neanderthal ancestry than Europeans. Others argue that European Neanderthal ancestry is diminished by later mixing with a human population without Neanderthal ancestry! Finally, some researchers have suggested these differences can be explained by natural selection, whereby Neanderthal genes are removed from the population due to their selective effects, which had different power across different populations (the larger the population, the stronger natural selection is)

Despite the widespread agreement about Neanderthal ancestry in modern humans, the discovery has triggered many more questions.

A new paper in PNAS, The Limits of long-term selection against Neandertal introgression, aims to resolve this muddle by two primary means:

  1. Use multiple Neanderthal samples of different relatedness to modern humans to obtain a better estimate of proportions.
  2. Add complexity to our understanding of the interactions between various ancestral human populations, and see how that affects estimates of Neanderthal ancestry.

The authors conclude that the decline in Neanderthal admixture discovered in Europeans may, in fact, be an artifact. First, it neglects gene-flow between African populations, as well as from Eurasian populations back into Africa (in particular, from European and Near Eastern groups). Second, using two Neanderthal samples, one much more closely related to the group which contributed to modern humans, allows for more precise direct estimates.

Though the authors found some evidence for natural selection, these results suggest that this force is not necessary to explain the differences between modern human populations.

This is unlikely to be the final world. The moral of the story is that moving beyond simple models and a few samples add complexity and nuance to our understanding of how our Neanderthal ancestry fits into the broader narrative of our ancestors’ tales.

Discover your Neanderthal story today!

To understand Neanderthals we need to understand ourselves was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

January 2, 2019

Onward to 2019!

Filed under: Genomics,Podcast — Razib Khan @ 11:57 pm

This was a big year for Insitome. Our three flagship products, Regional Ancestry, Neanderthal, and Metabolism, have been present in the Helix store for over a year. Over the next few months, we plan on upgrading and rolling out changes. One of the aspects of running a science-based service is that as the field evolves and changes, with dynamic technology we can update with the science. Watch for new “Traits” on our “Insights” over the next few months!

The Insight podcast produced over 40+ episodes. With over 150+ ratings on Apple, it is now one of the premier science-themed podcasts on the platform.

With 100+ posts on the blog, we are pushing forward with the project of complementing personal genomic products with information resources. The experience of receiving genetic results should be more than a one-time event. Insitome aims to provide continuous updates and revelations past on the latest science.

We’ll also be posting more updates to our YouTube website.

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

Onward to 2019! was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

December 19, 2018

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The Insight Show Notes — Season 2, Episode 10: 2018 in genomics was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

December 18, 2018

The year personal genomics got personal

Filed under: Genetics,Genomics,Technology — Razib Khan @ 1:12 am

The data for the above chart was assembled from press reports of various personal genomic companies with a public profile. So the values act as lower bounds. Additionally, the total numbers are from a comment in Genome Biology that I coauthored in the middle of 2018. Since then many more millions of people have been genotyped.

When Spencer Wells began The Genographic Project in 2005, genetic genealogy was an obscure and niche product. Today, consumer genomics has become a meme. Between January 1st of 2016 and January 1st of 2019, the total number of individuals who have purchased genotyping array kits increased 10-fold! From 2.5 million to closer to 25 million. An extrapolation would give a figure of 250 million individuals genotyped by January 1st of 2021.

This is at the root a story of science and technology. In 2005 it was rare for researchers to have access to the data of individuals who had tens of thousands of markers typed. By 2015 millions of Americans had purchased genotype arrays tested on themselves with hundreds of thousands of markers. From barely in the ivory tower, to the mass market. It has now become a business and cultural story. As 2018 ends the consumer genomics industry is now maturing, and expanding outward into the broader culture, as families now talk about their ancestry testing results over the holidays.

What does 2019 have in store? It is not implausible to imagine that the 50 million marks will be surpassed. At that point what was once a tool of the hobbyists will have left its stamp on the mainstream, and the public will begin to dictate what the “killer apps” of the sector are going to be.

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

The year personal genomics got personal was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

October 27, 2018

Laws of engineering are meant to be broken

Filed under: Genomics — Razib Khan @ 8:54 pm

A reader pointed out a very interesting passage in Richard Dawkins’ The Greatest Show on Earth: The Evidence for Evolution on the future possibilities of genome sequencing. Since the book was published in the middle of 2009, it is quite possible the passage was written in 2008, or even earlier.

Unfortunately for Dawkins’ prognostication track-record, but fortunately for science, he was writing at the worst time to make a prediction:

…the doubling time [data produced for a given fixed input] is a bit more than two years, where the Moore’s Law doubling time is a bit less than two years. DNA technology is intensely dependent on computers, so it’s a good guess that Hodgkin’s Law is at least partly dependent on Moore’s Law. The arrows on the right indicate the genome sizes of various creatures. If you follow the arrow towards the left until it hits the sloping line of Hodgkin’s Law, you can read off an estimate of when it will be possible to sequence a gnome the same size as the creature concerned for only £1,000 (of today’s money). For the genome the size of yeast’s, we need to wait only till about 2020. For a new mammal genome…the estimated date is just this side of 2040

Obsolete plot from The Greatest Show on Earth

The cost for a sequence here is somewhat fuzzy. The first assembly of a genome sequence of an organism is much more difficult than subsequent alignments of later organisms (though more in computation than in the sequencing). But, the upshot is that Dawkins was writing when “Hodgkin’s Law” was collapsing. From 2008 to 2011 Moore’s Law was destroyed by the sequencing revolution pushed forward by Illumina.

Though you can get a $1,000 consumer human sequence today, the reality is that this is for 30× coverage. For lower coverage, which means you aren’t as sure of the validity of any given variant, the price drops rapidly. And for the type of evolutionary questions Dawkins is interested in, the coverage needed is far lower than 30× (you probably want to get a larger number of samples than a single high-quality sample).

October 24, 2018

The crash of the cost of genome sequencing

Filed under: Genomics — Razib Khan @ 10:24 am

It’s been a wild 10 years. There’s a reason that data compression companies are a big thing in genomics now.

October 23, 2018

Reflections on ASHG Meeting 2018

Filed under: ASHG,Genetics,Genomics,Illumina — Razib Khan @ 10:17 pm

Another meeting of the American Society of Human Genetics has come and gone. I’ve been going since 2012, and so want to post some observations of how things have changed. This is a big conference. From less than 1,000 people in the late 1970s to nearly 10,000 today.

First, more genomics, less genetics.

The meeting dates to the late 1940s, and originally focused on the classical genetic analysis of human characteristics. Consider the pedigree one might find in a medical text.

Over the past generation more and more of the presentations and posters focus on genomics, surveys of the whole totality of our DNA sequence. This is where medicine and human genetics more generally is moving in any case.

Vendors such as Illumina loom large, but the firehose of data is so powerful that compression companies also arrive at ASHG. In other words, ASHG is a combination of a science, medical, and tech, conference.

Second, a major shift in focus outside of traditional European study populations.

ASHG foregrounded the focus on Africa and other non-European regions to highlight the importance of the capturing of global genetic variation. A fair number of presentations and posters were on this topic, as well as a series of plenary talks.

One thing I’ve noticed is that many talks and posters now present data and results which have been posted as preprints. In past years a lot of novel and new results were first presented at the conference, but now the meetings seem to be more like a halfway point between posting the preprint and the publication of the final paper. This means that networking and career development have become as important as the science itself.

Probably the most notable result that hasn’t been posted as a preprint was the first robust signals of association between genetic variations and homosexual orientation in men. Though there is a history of these reports, this one is clearly a case where the authors went through all the statistical checks to make sure these are true hits. Some in the audience reacted negatively, but the research group was really careful.

Exciting times in the world of genetics and genomics. Very excited for what 2019 brings.

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

Reflections on ASHG Meeting 2018 was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

September 18, 2018

On the whole genomics will not be individually transformative…for now

Filed under: Crispr,Genomics,Personal Genetics,Personal Genome,Personal genomics — Razib Khan @ 4:51 pm

A new piece in The Guardian, ‘Your father’s not your father’: when DNA tests reveal more than you bargained for, is one of the two major genres in writings on personal genomics in the media right now (there are exceptions). First, there is the genre where genetics doesn’t do anything for you. It’s a waste of money! Second, there is the genre where genetics rocks our whole world, and it’s dangerous to one’s own self-identity. And so on. Basically, the two optimum peaks in this field of journalism are between banal and sinister.

In response to this I stated that for most people personal genomics will probably have an impact somewhere in the middle. To be fair, someone reading the headline of the comment I co-authored in Genome Biology, Consumer genomics will change your life, whether you get tested or not, may wonder as the seeming contradiction.

But it’s not really there. On the aggrgate social level genomics is going to have a non-trivial impact on health and lifestyle. This is a large proportion of our GDP. So it’s “kind of a big deal” in that sense. But, for many individuals the outcomes will be quite modest. For a small minority of individuals there will be real and important medical consequences. In these cases the outcomes are a big deal. But for most people genetic dispositions and risks are diffuse, of modest effect, and often backloaded in one’s life. Even though it will impact most of society in the near future, it’s touch will be gentle.

An analogy here can be made with BMI, or body-mass-index. As an individual predictor and statistic it leaves a lot to be desired. But, for public health scientists and officials aggregate BMI distributions are critical to get a sense of the landscape.

Finally, this is focusing on genomics where we read the sequence (or get back genotype results). The next stage that might really be game-changing is the write revolution. CRISPR genetic engineering. In the 2020s I assume that CRISPR applications will mostly be in critical health contexts (e.g., “fixing” Mendelian diseases), or in non-human contexts (e.g., agricultural genetics). Like genomics the ubiquity of genetic engineering will be kind of a big deal economically in the aggregate, but it won’t be a big deal for individuals.

If you are a transhumanist or whatever they call themselves now, one can imagine a scenario where a large portion of the population starts “re-writing” themselves. That would be both a huge aggregate and individual impact. But we’re a long way from that….

September 14, 2018

Sequence them all and let God sort it out!

Filed under: Genomics — Razib Khan @ 11:14 am

Researchers reboot ambitious effort to sequence all vertebrate genomes, but challenges loom:

In a bid to garner more visibility and support, researchers eager to sequence the genomes of all vertebrates today officially launched the Vertebrate Genomes Project (VGP), releasing 15 very high quality genomes of 14 species. But the group remains far short of raising the funds it will need to document the genomes of the estimated 66,000 vertebrates living on Earth.

The project, which has been underway for 3 years, is a revamp and renaming of an effort begun in 2009 called the Genome 10K Project (G10K), which aimed to decipher the genomes of 10,000 vertebrates. G10K produced about 100 genomes, but they were not very detailed, in part because of the cost of sequencing. Now, however, the cost of high-quality sequencing has dropped to less than $15,000 per billion DNA bases…

Funding remains an obstacle. To date, the VGP has raised $2.5 million of the $6 million needed to sequence a representative species from each of the 260 major branches of the vertebrate family tree. To reach the goal of all 66,000 vertebrates will require about $600 million, Jarvis says.

Though a lot of the details are different (sequencing vs. genotyping, vertebrates vs. humans), many of the general issues that David Mittelman and I brought up in our Genome Biology comment, Consumer genomics will change your life, whether you get tested or not, apply. That is, to some extent this is an area of science where technology and economics are just as important as science in driving progress.

I remember back in graduate school that people were talking about sequencing hundreds of vertebrates. But even in the few years since then, the landscape has shifted. I’m so little a biologist that I actually didn’t know there were only ~66,000 vertebrate species!

And yet this brings up a reasonable question from many scientists who came up in an era of more data scarcity: what are the questions we’re trying to answer here?

Science involves people. It’s not an abstraction. Throwing a whole lot of data out there does not mean that someone will be there to analyze it, or, that we’ll get interesting insights. To be frank, the original Human Genom Project project should probably tell us that, as its short-term benefits were clearly oversold.

In relation to how cheap data storage is and the declining price point of sequencing, I think my assertion that a genome, a sequence, is not a depreciating asset still holds. There is the initial cost of sequencing and assembling and the long term cost of storage, but these are small potatoes. The bigger considerations are the salaries of scientific labor and the opportunity costs. Sequencing tens of thousands of genomes may not get us anywhere, but really we’re not going to lose that much.

Ultimately I side with those who believe that the existence of the data itself will change the landscape of possible questions being asked, and therefore generate novel science. But it’s pretty incredible to even be debating this issue in 2018 of sequencing all vertebrates. That’s something to reflect on.

May 9, 2018

The “X” in the sex chromosome

Filed under: Genetics,Genomics,mothers-day,science — Razib Khan @ 3:48 pm

There are ~3 billion base pairs in the human genome. Of that ~5% are in the X chromosome. The X is fully functional, unlike the famously hamstrung Y. It harbors one of the longest genes in the human genome, DMD, at 2,300,000 base pairs. In contrast, the human Y chromosome only has 72 protein coding genes! (it’s perhaps no surprise that, aside from sex determination, many of these genes are involved in things such as spermatogenesis)

And yet it is the Y chromosome which gets full treatment in popular science books. Like the C student who receives praise for a B-, the Y chromosome is given high marks simply for doing a few things here and there, most especially its role in driving the emergence of biological males. But the reality is that males would not be viable if it wasn’t for the X.

Can you see that it says 74?

Because the Y chromosome is so handicapped, filled with repetitive “junk DNA,” the heavy-lifting is shifted onto the single X that males carry. Though the Y is what makes males male, the X is what keeps males alive.

Anyone familiar with sex-linked characteristics knows this. Red-green color blindness is found 8 percent of human males and 0.6 percent of human females. Many more women are carriers of color blindness than who are color blind themselves.

The genes responsible for detection of some colors are found on the X chromosome, and are subject to high mutation rates. If a female has a broken copy she usually has a fallback in a functional second copy. She’s a carrier. In contrast, because males have only one X chromosome (inherited from their mother), they don’t have a backup. If a color-vision gene on the X chromosome is broken, then they’re out of luck when it comes to perceiving the full vibrancy of the world.

In other words, the male X chromosome does not possess recessive traits. All traits express due to the state of the single copy of the gene determining the trait. Every mutation on the X chromosome can potentially produce a mutant that will be exposed to natural selection.

Neanderthal-modern human hybrid

This results in some interesting evolutionary quirks when it comes to how natural selection shapes the genome and drives adaptation within populations and speciation between them. Crosses between different species can leave hybrids infertile. In mammals this often happens in males because mutations on the X chromosome can interfere with proper reproductive development. Selection against the genes of other species then happens because males can’t produce offspring.

Studies of Neanderthal admixture confirm this — there is far less Neanderthal ancestry on the X chromosome than across the rest of the genome. There is strong selection against Neanderthal variants in males, because these genes work less well with the rest of the modern human genome.

A wife of Genghis Khan

But the X chromosome is not distinctive just in terms of just natural selection. As two out of three X chromosomes in any population are found in females, its genetic history will be biased toward that sex. Differences between the X chromosome and the non-sex genome can tell us differences in the histories of men and women.

For example historically many more of the female ancestors of admixed people of the New World tended to be non-European, whether it was indigenous or African. As such, the genetic profile of the X chromosome in terms of similarity to worldwide variation would be different from the non-sex chromosomes, because those come equally from the father and mother. This is exactly what we see. There is less European ancestry on the X chromosome.

More generally mating systems such as polygyny — men having multiple female partners — result in far fewer males than females who contribute to future generations. Among Mongols during the era of Genghis Khan, a small number of males descended from Genghis and his Mongol horde had children with numerous women. Because X chromosomes tend to found in women, more of whom are reproducing, they will more diverse than non-sex chromosomes (where a few men contribute half the genes), while the Y chromosome will be the least diverse of all (where only a few men contribute genetic variation).

Men have only one X chromosome, but the one they have is genetically essential to them. X chromosomes are not exclusive to women, but for all males they are the singular legacy of their mothers. Because of this bias the X can shed light on the history of the women of our species, while the uniqueness of inheritance the X chromosome may even extend to driving the emergence of our species.

Explore your Neanderthal story today.

The “X” in the sex chromosome was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

April 25, 2018

DNA, from genetics to genomics

Filed under: DNA,Genetics,Genomics,science — Razib Khan @ 11:59 am

In the early 1950s scientists established that the molecular structure of DNA was a double helix. The had discovered the physical substrate of heredity. With this discovery the field of molecular genetics was born (and eventually a Nobel Prize given!).

And yet we also know that Gregor Mendel discovered the laws of heredity, the “law of segregation” and the “law of independent assortment”, nearly a century before the discovery of DNA.

It was literally the product of a garden.

The mature field of genetics itself developed fifty years before the discovery of the structure of DNA, as a host of scientists stumbled upon Mendelian insights simultaneously. Most were biologists who worked with plants, flies, or even algebra — no need for a powerful microscope or structural models of molecules.

Though DNA has been the key to many of the discoveries of the past fifty years, it is important to remember that the field of genetics is predicated on an abstract understanding of how inheritance works across pedigrees, as opposed to the biophysical basis of that transmission. Before DNA, before chromosomes, what Mendel and his heirs understood is that inheritance occurs through a process where discrete units of heredity, “genes”, are passed down from generation to generation.

These genes usually come in two copies, ‘alleles,’ for many organisms.

Recessive expression patterns of a trait, where parents do not express a characteristic found in their offspring, becomes comprehensible when a Mendelian model is adopted. Prior to this many had an intuitive “blending” understanding of inheritance, where the characteristics of the parents mixed together to produce offspring. The ultimate problem with blending inheritance is that it had difficulty in explaining how variation persisted over time. A problem solved by the Mendelian insight that genetic variation never disappeared…it simply rearranged itself every generation!

Genetics was born on the backs of Drosophila

Between the reemergence of Mendelian thought around 1900 and the discovery of DNA in the 1950s much research occurred in the field of genetics. The Neo-Darwinian Synthesis built upon the mathematical foundations of population genetics, which took the Mendelian framework and formalized and extended them, to create a model of evolutionary biology for the 20th century. Medical geneticists began to understand the patterns of inheritance of rare diseases in humans with the aim of preventing illness. Those researchers working with fruit flies discovered many of the phenomena which define modern genetics, such as recombination. Finally, biochemists established that heredity and nucleic acids were intimately connected.

Just as an understanding of the discrete basis of inheritance in a Mendelian framework opened up the systematic scientific study of heredity, so the understanding of the double helical structure of DNA paved the way for the molecular revolution of the second half of the 20th century, and the genomic revolution of the 21st. An understanding of DNA as the mode of inheritance allowed for the development of techniques that traced transmission of variation at the level of genes themselves, as opposed to expressed traits.

Illumina sequencing machine

And while in the 20th century we spoke of genetics, and specific genes, today we speak of genomes and the whole set of genes organisms possess. That revolution can not be understood without the knowledge of DNA as the mode of inheritance. If classical Mendelian genetics is pattern recognition across pedigrees, 21st century genomics is a synthesis of classical genetics, post-DNA era biophysics, and cutting-edge computing. Genomics is as much engineering as it is science; and “big data” as much as information theory.

The understanding of DNA created the world where genetics transformed itself from an esoteric science of probabilities, to a mass market product of possibilities.

Classical genetics tells you that your relatedness to your brother or sister is expected to be 0.50. Modern genomics might tell you that your relatedness to your brother or sister is shared across 46.24% of your genome. A fuzzy probability becomes a crisp reality. As a science, genetics can be imagined without DNA. It was born and matured decades before we understood the importance of the double helix, but as a part of our lives, one can’t imagine genetics without DNA.

Learn more about where your traits for food tolerance fall on the spectrum and explore your Metabolism story today.

DNA, from genetics to genomics was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

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.

Older Posts »

Powered by WordPress