Selection for height in ancient Europe

Screenshot - 10262015 - 05:22:41 PMIain Matheison, first author of Eight thousand years of natural selection in Europe, has a short note up at his website, Selection on height in Europe. He concludes:

More generally, it seems strange that height is the only trait for which a robust signal of polygenic selection has been observed. It’s hard to imagine that traits like diabetes risk and lipid levels were not also under selection in this period. I think it’s mostly down to lack of power in the predictors for other traits. Possibly larger GWAS and better predictors will reveal more. Finally, most of the work in this area has focussed on Europe, since that’s where the large cohorts are. But similar dynamics must also have happened in the rest of the world and it’s only by looking at other populations that we’ll be able to understand more generally the process of human adaptation.

North Chinese are also taller than South Chinese. And there are many quantitative traits in humans. We’re living in a golden age of phylogenomic analysis of humans in particular, but at some point in the near future the lens will begin to turn back onto classical population genetic questions of the parameters which shape the nature of variation. The initial wave of enthusiasm for selection scans ~2005 seems to have abated somewhat, but I think it’s only a slight pause, as polygenic selection and “soft sweeps” come onto the radar of genomicists….

Open Thread, 10/25/2015

Today I got on the internet after spending the morning with my kids and then lifting with a friend, to see Tyler Cowen say this: “this is one of the very best non-fiction books of the year,” in relation to . I’ve read a fair amount on the Mongols conquests and Central Asia in general (e.g., or ). And, I’ve also read the author, Frank McLynn before. His , could have been a bit more thoroughly edited. People ask me how I figure out which books to read. One of them is by strong recommendations from people whose judgement I don’t think is crazy. I don’t know Tyler Cowen that well, and he’s not a god in my universe, but he decided to type out “one of the very best non-fiction books of the year”, and it’s on a topic which I’m already somewhat interested in, then of course I’m going to read it (also, at 700+ pages, there is a high possibility of lots of information per unit of cost).

When people try to talk about cross-cultural comparisons I often tell them to shut up. For example, let me mention the reader (who I will not name though I know this person continues to read me) who could not think of any non-Western thought which expressed the sort of altruistic ethos reminiscent of the Christian Gospel (this reader was not at the time a Christian by the way). When I asked if they knew of the thinkers of ancient China they admitted they were only very familiar with Western works. Which immediately prompted me to ask how they could make a comparative judgement in the first place.

This is a reminder to readers that though any truly educated person does not need to know the works and thought of all societies across history, one does need to sample more than one. I have long thought one of the most important figures in fact, if not legend, in Chinese history was Xunzi, who influenced both later Confucianism as well as Legalism. And, as it happens, there is a of his thought, striking the right balance between being overly academic and excessively abridged. Last week I promoted , so this week I thought I should balance it out.

Obviously still very busy with things since coming back from ASHG. My blogging productivity tends to be a bit punctuated…. You know how it goes.

When sequencing makes genotyping obsolete (soon)

Historic_cost_of_sequencing_a_human_genome.svgFor several years there has been a nerdy debate in some labs about sequencing vs. genotyping (more precisely, doing genotyping-by-sequencing vs. going with an array). There are many pros and cons. If you are working on non-model organisms there may not be a good SNP array for you, so the decision is done. If you work on humans in contrast there are several options which are rather affordable. But at some point I assume that sequencing will get so cheap that that SNP array technology will be rendered obsolete, rather like what RNA-seq is doing to microarrays. Currently the cost of sequencing has not declined much for a few years, as Illumina basically squeezes de facto monopoly allowable price out of customers. At some point in the near future this monopoly will break, with the current bet being on a Nanopore driven disruption of the space. Then the collapse in cost by base genome will commence again, until the technology gets good enough that it’s not really the rate limiter in the pipeline.

With the announcement that 23andMe is increasing their price, from $99 to $199, it got me to thinking about comparing sequencing vs. genotyping. You see, 23andMe uses a SNP-chip. Last I checked just under one million markers, with a custom set of 30,000 added on to the standard Illumina set. They’ve got over one million people genotyped, so they’ve been at this for a long time. But is $199 worth it for a one million markers? As regular readers know I’ve been following the progress of the small start-up Full Genomes for a while. You can get WGS elsewhere, but this group has been very proactive about attempting to cultivate a retail presence (that is, direct-to-consumer). Their prices are on their website, but below is a comparison chart:

Company Service Cost Time User-friendly How much of genome?
Full Genomes 30x coverage $1,850 Months No Medical grade accuracy of whole genome
Full Genomes 10x coverage $745 Months No Not medical grade, but probably whole genome
Full Genomes 4x coverage $375 Months No Will have gaps in genome, but most
Full Genomes 2x coverage $250 Months No Lots of gaps in genome, but a lot of it
23andMe 1 million marker SNP $199 Weeks Yes Accurate genotype calls 1 million out of 5 million variants

Basically coverage is telling you how many times a marker is going to come back in the raw results. If there an error in one particular position you can figure that out pretty easily if you expect to have sampled it 30 times. In contrast, if you have only one read to look at for a position then if it’s not matching the reference it is highly like you’re seeing a false positive. For evolutionary genomics work low coverage is really not a major issue, because you’re curious about population wide dynamics. But if you want to make accurate calls which are medically actionable, then you need to be confident, and for that you need to have high depth on your coverage. With >30x you’re catching almost all the variants in your genome, and so can pick up things like mutations novel to you, which wouldn’t come back on a SNP-array in most cases, since they’re ascertained on common variants.

Since I knew Full Genomes‘ cost chart I knew that their 2x sequencing is now approaching the genotyping results provided by 23andMe in terms of apples-to-oranges cost comparisons. I say apples-to-oranges, because the truth is that Full Genomes is providing a different service. It’s very much of a “rough cut,” while 23andMe is delivering turn-key personal genomics. But, if you are comfortable with .bam and .vcf files, then now is the time to actually consider sequencing (though from what I know Full Genomes‘ turnaround time is on the order of three to six months, while 23andMe is closer to one month). For me the sweet spot right now would be 10x, as 30x is probably overkill, especially if you already have genotype data and are comfortable with imputation….

23andMe is back; but a higher price for fewer results?

23andme_logoIf you’re not sleeping under a rock, you know that today 23andMe has rolled out its plan to provide government (FDA) approved medical results. In the generality I knew this was in the offing. I asked contacts within the company, and they pretty much signaled this was imminent, though they didn’t detail the specifics. This is a big deal because for a lot of people the medical results are big reason you’d get the service. Certainly I have friends who have been waiting for years, who kept asking when this would happen, as then they could the pitch to family to get typed.

But there’s a minor hitch: you’ll be charged more for fewer results. They’re going to be jacking up the price to $199 from $99. Arguably the results they’ll be giving you are more robust than the older full suite, but basically 23andMe is increasing prices, while giving customers a leaner deal than many of us were used to before the FDA clampdown (also, carrier testing is provided pretty much free for many people with insurance if you are going to have a child).

The question then emerges for the rationale behind this price increase. After all, in the tech sector it’s not the norm to charge more for less after users have become used to a particular price point. My own hunch is this: with well over 1 million customers they’re going to aim to squeeze more information out of their current user base than gain more customers. From what I had heard, 23andMe was basically losing on customers in the initial years to grow their data set. But recently SNP array have become cheap enough that on paper they’d actually be making a profit by pushing their product for $199 if you just took the array price into account.

I’m a little disappointed in the particular turn of events, though overall I stand by my assertion from two years back that these bumps in the road will be little in the long run. The future is coming at us, at varying rates of increase or decrease, but always with a positive velocity.

Dogs most likely to be from the heartland

Screenshot - 10192015 - 03:36:05 PM
Screenshot - 10192015 - 03:51:57 PMThe media is blowing up with a new story about the phylogeography and phylogenetics of the domestic dog.* The New York Times has a good write up, and I like its title: Central Asia Could Be Birthplace of the Modern Dog (the headline was changed to “15,000 Years Ago, Probably in Asia, the Dog Was Born” while I was writing this post, which strikes me as even more tentative). The conditional clause is pretty important, because this is not definitive, but suggestive. The paper is titled Genetic structure in village dogs reveals a Central Asian domestication origin, but the text itself is a lot more qualified than the title might let on. There are many more chapters to this story to be told.

Screenshot - 10192015 - 04:54:55 PMThe issue of the where dogs came from is kind of a big deal. There have been claims for the origin of dogs in East Asia, Middle East, and Europe. If you look at these papers there are major issues in terms of the underlying data used to make these inferences (e.g., the East Asian argument relies on Y lineages, while the arguments favoring Europe are based on mtDNA, with a particular comparison to ancient genomes from Europe, and the Middle Eastern result turns out to have had issues of sample bias). To be fair, you can only make arguments based on the data you have on hand. But, the track record for humans should make us careful about that in relation to strong general inferences.

A big upside of this particular paper is that the massive geographic coverage. This took a lot of work, as I discussed this with Ryan Boyko (second author) a few years ago (dogs can be ornery and village dogs in particular are not hygienic creatures). Additionally, as they note they use a “semicustom” SNP-chip, with nearly 200,000 markers. This is sufficient density in mammals for most inference, and is probably overkill for breed analysis which used to be the bread & butter of dog genetics. As you can see from the PCA plot, a lot of the genetic variation is partitioned by geography.

Basically, dogs at some point diverged from a common ancestor, and accrued variation which distinguished lineages by region. Second, the spread of European origin dogs is a major dynamic which affects much of the world. In the paper itself the authors mention that there’s going to be some ascertainment bias in their sample set toward this admixture in non-European lineages because of the concentration of post-colonial lineages in cities. You see similar patterns with domestic cats, which is an organism I know better. A rule of thumb seems to be that if Christianity was successful a region, the local domestic lineages may also have been swamped (perhaps this is correlated with cultural complexity, which are correlated with dogs well adapted toward resisting invasive European dogs?). Nevertheless, there are interesting populations like the Carolina dog which preserve pre-European lineages.

The major finding, allowed by their geographic finding, is that Central Asian dogs exhibit evidence of a long ago bottleneck in their genome due to their pattern of linkage disequilibrium (LD). LD can be thought of as a violation of Mendel’s law of assortment on a biomolecular scale. Genetic variants at different loci are co-inherited together at a higher fraction than would be the expected case if they were segregating in the population independently (e.g., if allele A and a are both at 0.5, and B and b are 0.5, then A should be found in equal proportion associated with B and b, but in a case of LD it wouldn’t be). In a physical sense one can imagine these as haplotypes, sequences of variation across the genome, where particular alleles are often found on the same segment.

All this is important as LD is a signature of different demographic events, including the bottleneck above. When you have a very recent admixture between two populations you get elevated LD. Adjoining ancestrally informative alleles take generations to disassociate from each other through of recombination. But bottlenecks can also induce increased LD, as particular haplotypes increase rapidly in frequency through sampling processes. Populations which have gone through sharp recent reductions in population will exhibit long range LD. LD between alleles which are posited relatively far apart on a genomic scale. Over time recombination breaks apart these associations, and LD gets shorter and shorter. This “decay” in LD over time has been used to peg admixture dates, but in this case the authors note that:

LD is lowest in Afghanistan and Central Asia at short inter-SNP distances (< 0.0005 cM) and lowest in Vietnam at intermediate distances (0.01–0.05 cM), with rates increasing in other populations depending on their isolation and distance from Asia. These patterns of LD decay strongly suggest a Central Asian origin for domestic dogs with a subsequent population expansion (larger contemporary Ne) in East Asia and elsewhere. These patterns are consistent if physical, rather than genetic, inter-SNP distance is measured, or if different subsets of dogs are used for each population

To my mind there are two other major reasons that it is likely that Central Asia is a highly likely candidate region for the origin of modern domesticates. Simply, and alluded to in the paper, is that Central Asia is in a central position in relation to the full pre-Columbian range of the species. The likelihood from all the genetic evidence is that dogs are descended from a population similar to Eurasian wolves; so their locus of origin has to be in the Palearctic ecozone. Second, there is archaeological signs that canids with a dog-like morphology arose very early here. Ancient DNA also lends some support to this supposition.

Is this is a slam dunk case? Not at all. As some commentators have pointed out, at a certain level of granularity inferences from extant variation have limited utility. But the question is the level of granularity…modern human origin in Africa inferred from archaeology, mtDNA, and microsatellites, have been broadly supported. This seems to be the scale that this sort of paper is targeting.

The second major issue that this paper tries to pin indirectly is the period of domestication. They converge upon the date of ~15,000 years before the present, which seems to be the new mainstream/conservative estimate. An ancient DNA paper which was published this spring though pushes the possible date as far back as ~40,000 years before the present. Additionally, dogs moved with humans, and it strikes me that if the Amerindians brought dogs with them, then a date of ~15,000 years is close to the lower bound (the distribution of dates isn’t symmetrical).

In a few years, with lots of whole-genome analyses with this level of geographic coverage, as well as ancient DNA, I expect that some of the story above will be confirmed, but the overall picture is likely to be complex and more bizarre than we would expect. I say that because it seems very unlikely to me that dogs are going to be any simpler a story than that of humans. If the vast majority of Northern Europeans were replaced ~5,000 years ago, was there a concomitant replacement of dogs? Some ancient DNA indicates replacement, just as has been the case with humans. It seems likely that large animals during the Pleistocene underwent complex meta-population dynamics of extinction and recolonization several times. One can imagine a scenario where the vast majority of modern dog ancestry derives from Central Eurasian ~15,000 years before the present, after the Last Glacial Maximum, but where threads of more diverged ancestry persist in some populations, not to mention acknowledged gene flow from local wolves.

At the end of the day, if someone made me bet where the ancestral lineage which diverged from the ancestors of Eurasian wolves flourished, I would say Central Asia. But, my confidence in this assertion is only moderate, and it seems likely that even this simple answer might mislead us as to the complexity of the bigger picture. I suspect we’ll known the answer within the next five years.

Addendum: This paper has some of the first large scale analysis of Y chromosomal SNP variation. Intriguingly they found “We also see indigenous Mt haplotypes segregating in Carolina dogs and Xoloitzcuintlis, but no unique Y haplotypes indicative of indigenous ancestry were found in American dogs outside of the Arctic.” This strangely recapitulates sex-biased gene flow in the New World for humans, indicating that the story of man and his best friend exhibit more similarities than we might have thought.

* I should add that several of the authors on this paper are friends.

Open Thread, October 18th, 2015

I’ve obviously been a bit remiss with the blogging. That will change in the near future. First, ASHG was the bomb. I also hit D.C., New York, and Cambridge, in rapid succession. Lots of people to meet and catch up with. But a week away meant that other responsibilities built up and I’m just trying to make it through the enormous backlog.

So I recommended Bobbi S. Low’s a few months ago to a friend who was curious about this topic. But I realize it’s way out of date. I’m not really super interested in sex differences because the basic outlines, like psychometrics (to name another example), seem to be pretty well established. There are some traits, like intelligence, when on average men and women are about the same (granting likely tail differences). There are other behavioral traits where the distributions differ. And, there are traits like upper body strength where men and women are nearly disjoint in their distribution. But in today’s world these sorts of issue are not treated dispassionately nor are they disputed. Rather, there’s a confusing morass where gender and sex are are play. On the one hand gender is a social construction, but on the other hand some transgender individuals are “born” with “female” brains. The quotations here because this sort of phrasing would not be socially acceptable in other contexts, but becomes magically normative in transgender contexts when one goes to arguing the equal standing of trans-women (those born biologically male) to cis-women (those born biologically female).

I’m not particularly interested in this social or political debate. But, I’m curious if there is a up-to-date monograph on sex differences. That way I could recommend something more contemporary to people who are interested, since this is a field that needs to be rediscovered by youth.

I’ve been reading in passing now and then when I have a little time. When I was a small child I was a big admirer of Alexander the Great. After all, when it came to conquering he exhibited virtuosity. But as I have matured into adulthood I’ve come to be more wary of the rather unsavory aspects of the Macedonian warlord’s character (e.g., killing close friends in drunken rages). Marcus Aurelius stands in contrast to Alexander in many ways. While the Macedonian aspirant world emperor burned bright and chaotically, the last of the Good Emperors spent his reign attempting to maintain the semblance of the peace which he had inherited against the inevitable forces of chaos and disorder which were creeping into the sclerotic system of the polity which had arisen in the time of Augustus over 150 years before.

Marcus Aurelius was no saint. He was a man of his times, who countenanced persecution of Christians, and did nothing to end practices such as slavery which we today would consider abominations. Additionally, itself was a piece of personal propaganda, meant to be read by others. It was never the unguarded thoughts of the most powerful man in the world. But, a man like Marcus Aurelius reminds us that in some things the ancients may have been superior to the moderns. Set him against the politicians of the liberal democratic states of our day, and I believe that he would be superior to them all. Of course, a man like him would probably not go into politics in our day.

Everyone is talking about Ancient Ethiopian genome reveals extensive Eurasian admixture throughout the African continent. I think the results are fine, but the interpretation is wrong. Africa is big, and the admixture is too recent and even outside of Northeast Africa. I will probably say more soon.

Also, ~80,000 year old modern human remains from China. Let’s take the estimates at face value. Considering that the Aurignacians left no genetic imprint on Europe, it is not implausible to me that this population, two times as old as that group, left no imprint on East Asia. In fact, one might posit a model where “modern humans” on the edge of the range expansion in Eurasia generally left no descendants, and that modern West and East Eurasians descend by and large from a later pulse from somewhere around the Middle East.

Some doctors don’t live in the real world

When Genome Sequencing Tells Too Much, Doctors May Have To Keep Secrets:

In the case of a parent requesting to actively seek out early-onset markers for predispositions of diseases like breast cancer for their child, Sharp said a responsible physician would deny them the sequence unless that parent was able to provide a valid reason. The medical community generally advises against it because it would force them to navigate through new territory fraught with unpredictable challenges.

“We’re going to have to find the right ways to curb our enthusiasm for genetic testing,” Sharp said, “and really limit genetic testing only to situations that we have reason to suspect are going to be useful to the patient’s well being. Excessive testing can cause distress, raise cost, and generate information that ultimately doesn’t have any clinical utility.”

I’ve said enough that I don’t want to repeat myself. But it’s totally crazy talk to think that parents who are rejected by a doctor or institution when it comes to a whole genome sequence wouldn’t just go elsewhere. Perhaps these doctors who advise this tack think that in this way they’re absolving themselves of the responsibility?

Rather than attempting to deny the dissemination of information a more plausible, and frankly just, path would be to develop better means of interpretation for the public. Medical institutions arose in the 20th century, during an era of vast centralized organizations. That mentality seems to have carried over. But this is going to be a century of decentralization and commoditization of many technologies which were once the purview of the elite.

Rapture for the discerning non-model biologist

Screenshot from 2015-10-13 00:47:37

Very excited that a pre-print I’ve seen come into focus over the past year by my labmate Omar is finally out, RAD Capture (Rapture): Flexible and efficient sequence-based genotyping:

Massively parallel sequencing has revolutionized many areas of biology but sequencing large amounts of DNA in many individuals is cost-prohibitive and unnecessary for many studies. Genomic complexity reduction techniques such as sequence capture and restriction enzyme-based methods enable the analysis of many more individuals per unit cost. Despite their utility, current complexity reduction methods have limitations, especially when large numbers of individuals are analyzed. Here we develop a much improved restriction site associated DNA (RAD) sequencing protocol and a new combinatorial method called Rapture (RAD capture). The new RAD protocol improves versatility by separating RAD tag isolation and sequencing library preparation into two distinct steps. This protocol also recovers more unique (non-clonal) RAD fragments and produces better data for both standard RAD and Rapture analysis. Rapture then uses an in-solution capture of chosen RAD tags to target sequencing reads to desired loci. Rapture combines the benefits of both RAD and sequence capture, i.e. very inexpensive and rapid library preparation for many individuals as well as high specificity in the number and location of genomic loci analyzed. Our results demonstrate that Rapture is a rapid and flexible technology capable of analyzing a very large number of individuals with minimal sequencing and library preparation cost. The methods presented here should improve the efficiency of genetic analysis for many aspects of agricultural, environmental, and medical science.

This is very much about the methods, but there’s some interesting fish-genomics results, too. More of that in the next year or so. We can’t all be human or model-organism biologists, so this is excellent for those working in ecological, conservation, and more broadly non-model contexts. For a lot of this work, and population-genomic research as well, you don’t need medical-grade 30✕ whole genome coverage. That being said, this being a pre-print which is going to be revised and submitted, I’d suggest that Omar remove the stuff about medical utility. That’s a domain where they’ll kill them with coverage and the best technology, not the most cost-effective one.

It all began at Ararat, and Esau’s revenge


About four years ago the genome blogger Dienekes Pontikos published a post, The womb of nations: how West Eurasians came to be. The argument was that the genetic variation we see around us across western Eurasia and northern Africa has its ultimate roots in the the structure that was extant in the ancient Near East, near to the zone of initial agricultural innovation in the hills above the modern nations of Syria and Iraq. It was similar to the thesis of Peter Bellwood in . The model as outlined by Dienekes suggested that local substrate was absorbed as these initial agriculture societies rapidly swept outward from their initial focal zone. In the broadest strokes I do think that he, and Bellwood, were correct from what we now know.

Ancient DNA in Europe strongly indicates massive . But, there is also suggestion of admixture with the local substrate. And, unlike the stylized model of Bellwood, it seems that there were multiple migrations after the initial pulse which reshaped the genetic and cultural landscape of human societies in the wake of agriculture. Here is the abstract for Lazaridis et al. at ASHG:

It has hitherto been difficult to obtain genome-wide data from the Near East. By targeting the inner ear region of the petrous bone for extraction [Pinhasi et al., PLoS One 2015] and using a genome-wide capture technology [Haak et al., Nature, 2015] we achieved unprecedented success in obtaining genome-wide data on more than 1.2 million single nucleotide polymorphism targets from 34 Neolithic individuals from Northwestern Anatolia (~6,300 years BCE), including 18 at greater than 1× coverage. Our analysis reveals a homogeneous population that is genetically a plausible source for the first farmers of Europe in the sense of (i) having a high frequency of Y-chromosome haplogroup G2a, and (ii) low Fst distances from early farmers of Germany (0.004 ± 0.0004) and Spain (0.014 ± 0.0009). Model-free principal components and model-based admixture analyses confirm a strong genetic relationship between Anatolian and European farmers. We model early European farmers as mixtures of Neolithic Anatolians and Mesolithic European hunter-gatherers, revealing very limited admixture with indigenous hunter-gatherers during the initial spread of Neolithic farmers into Europe. Our results therefore provide an overwhelming support to the migration of Near Eastern/Anatolian farmers into southeast and Central Europe around 7,000-6,500 BCE [Ammerman & Cavalli Sforza, 1984, Pinhasi et al., PLoS Biology, 2005]. Our results also show differences between early Anatolians and all present-day populations from the Near East, Anatolia, and Caucasus, showing that the early Anatolian farmers, just as their European relatives, were later demographically replaced to a substantial degree.

A somewhat different abstract was submitted for a meeting in Germany:

We study 1.2 million genome-wide single nucleotide polymorphisms on a sample of 26 Neolithic individuals (~6,300 years BCE) from northwestern Anatolia. Our analysis reveals a homogeneous population that was genetically similar to early farmers from Europe (FST=0.004±0.0003 and frequency of 60% of Y-chromosome haplogroup G2a). We model Early Neolithic farmers from central Europe and Iberia as a genetic mixture of ~90% Anatolians and ~10% European hunter-gatherers, suggesting little influence by Mesolithic Europeans prior to the dispersal of European farmers into the interior of the continent. Neolithic Anatolians differ from all present-day populations of western Asia, suggesting genetic changes have occurred in parts of this region since the Neolithic period. We suggest that the language spoken by the homogeneous Anatolian-European Neolithic farmers is unlikely to have been the same as that spoken by the Yamnaya steppe pastoralists whose ancestry was derived from eastern Europe and a different population from the Caucasus/Near East [Haak et al. 2015], and discuss implications for alternative models of Indo-European dispersals.

And now, David has a post up, Yamnaya’s exotic ancestry: The Kartvelian connection. You can read the post yourself, but he presents TreeMix results which strongly imply that the Near Eastern gene flow into the Yamnaya population derives from one with a relationship to modern Kartvelian groups, the most prominent of which are Georgians. This is not entirely surprising. I’ve seen similar things, though I’m not sure what to think of this. Going back to Dienekes’ post he suggests that “It is, perhaps, in the ancient land of the Colchi, protected by the Black and Caspian seas, and by tall mountains on the remaining sides, that something resembling the ur-population survived.” That is, the people of the trans-Caucasian region may preserve elements of the deep ancestral heritage of the Middle East which was to some extent effaced by later migrations. I have some Assyrian genotypes, and this population has strong affinities with Armenians and Georgians. Additionally, I believe that much of the west Eurasian heritage in South Asians is from this same region and source. In Genetic Evidence for Recent Population Mixture in India the authors note that “For all 45 Indian groups on the Indian cline…we find that Georgians along with other Caucasus groups are consistent with sharing the most genetic drift with ANI [Ancestral North Indians -Razib].” Of course in South Asia there was a second intrusion of this sort of ancestry, but in this case as part of the admixed compound brought by Indo-Europeans, who interleaved Near Eastern, ancient European, and Central Asian, all in one.

There are two elements here which need to be noted. First, a genetic one in regards to the Middle East. In Europe over thousands of years the heritage of the first farmers waned, as that of the hunter-gatherers experienced some resurgence, and eventually the Indo-Europeans from the steppe overran vast territories. In the Middle East analogous groups which expanded out of the ancient hillocks and swept south were overwhelmed by a later Arabian reflux. These are perhaps prefigured by the drifting of Amorites into the cities of ancient Mesopotamia 4,000 years ago, and more recently the arrival of Arabs who had been outside of the limes of civilization into the worlds of eastern Rome and western Persia.

Finally, this is about the nature of culture and the advantage which a particular toolkit does, or doesn’t, provide a people. The rollover of European hunter-gatherers, or the fact that “Ancestral South Indians” (ASI) don’t exist in pure unadmixed form, point to the advantages which a fully elaborated agricultural cultural system provided the farmers. But, during the initial stages of the development of this toolkit it does not seem that there was any particular advantage to single group in a narrow delimited zone. To be more concrete, the linguistic diversity of the Caucasus region, or what we see and know from the edges of history in the Near East, may be close to the reality of the period of the early Neolithic in the Near East. Different polities with radically different languages, and likely divergent genetics, were all crystallizing the new lifestyle in a cheek by jowl fashion in the hills between the Tarsus and Zagros mountains. At some point though the system became powerful enough that it was portable and extendable in space. Rather than engaging in inter-group competition against populations which were comparable, the most successful route was to expand outward into the vast “unoccupied” zones of hunter-gatherers.

Because of the nature of climate west and east migrations were probably easiest and more rapid. Likely this resulted in a near total translocation of the ancestral cultures on far shores or distant horizons. But as the groups pushed north or south the agricultural toolkit was less well suited, and so synthesis with the native substrate was necessary. I believe that Indo-European and Afro-Asiatic may both be language families of hunter-gatherer populations who absorbed migrating farmers into a radically different ecology where the competitive playing field was much more level than in the initial zone of expansion.

New York City area codes are particularly “sticky”

The vast majority of the phone conversations I have with people are either on cell phones of via Skype. One of the consequences of this is the changing of the norms and expectations which accrued with telephone usage over the 20th century. For example, I don’t really know anyone’s number (does anyone know anyone’s “Skype number”?). Another dynamic I’ve noticed is the phenomenon of “sticky area codes.”

I’m going to be in Baltimore starting Wednesday and into Friday for ASHG. So I decided to email an old friend who I know from the Bay area, but who is actually a friend from my elementary school years back in the Northeast. When we both lived in the Bay we had atypical area codes. Mine was form the Northwest. His was from a New York City area code (where he went to medical school). It was absolutely no surprise to me that though he now lives in Baltimore he still has the same area code. I have other friends who have spent more than 10 years in the Bay area who retain their New York City area codes.

Here’s my hypothesis: the churn in area codes on cell phones over the past 15 years or so is basically modeled as neutral, with the exception of a few “prestige” area codes. As pointed out until recently area code portability wasn’t without friction. In particular you might have to get a new code (aligned with your residence) if you were switched carriers and such. But all that said, the prediction is rather straightforward, over time the proportion of prestige area codes should be increasing when you control for confounds. In regards to confounds, prestige area code residents were probably early adopters of cell phone technology. But now that the market has saturated and area code transition is relatively without friction my prediction is that there are is a notable bias in transitions away from non-prestige area codes, while prestige code holders are less likely to “mutate.”