After reading the supplements of the La Brana hunter-gatherer paper I have a few extra thoughts in a very general sense. One result you see on PCA plots with Europeans is that the La Brana sample (along with the Swedish hunter-gatherers) are shifted toward modern Northern Europeans, and to some extent even Finns. Obviously this is noteworthy because they don’t cluster with modern Spaniards (even Basques). But when you plot them on a world-wide distribution you see something else: the La Brana individual is the most shifted toward Asians of any of the European samples (this includes British, Iberians, Utah whites, Finns, and Tuscans). This isn’t due to cryptic East Asian ancestry. Rather, it’s that Paleo-Siberian ancestry which can be found in many West Eurasians and Native Americans. This is  in contrast with the Luxembourg hunter-gatherer which is dated ~1,000 years earlier than the La Brana individuals. I don’t know if the dates are reliable enough, but it seems plausible enough that there may have been events of demographic change on the scale of 1,000 years in ancient Europe.

To get a better sense they used D-statistics to estimate possible admixture/relatedness between Mal’ta and various populations. A negative value indicates more drift shared between H2 and H1 (admixture, gene flow, common ancestry, etc.). Sardinians are a European floor for “Ancestral North Eurasian” (ANE), which the Mal’ta individual represents. La Brana is statistically significantly more related to Mal’ta than all tested populations except for Orcadians and Russians. It is more shifted, but not to a statistically significant degree in those cases. The main qualification I want to add here is that Lazaridis et al. have reported that there is a “Basal Eurasian” population which has admixed across Western Eurasia, and increases the distance between Mal’ta and the populations with which it has mixed. The farmers which introduced agriculture to Europe seem to have brought this element, and it is found at a high fraction in the Caucasus, explaining the value for the Adygei. In fact the Adygei have more not less ANE than Northern Europeans. Since the La Brana individuals likely lack Basal Eurasian that could be affecting the D-statistics, inflating the implied ANE in the La Brana.

With all that qualification, it does seem that these La Brana individuals have genetic affinities with populations as far afield as Central Siberia, and the New World (via these Siberians). Additionally, like the other ancient European hunter-gatherers it exhibits signs of reduced genetic diversity compared to modern populations. What are we to think of this? In the broad view this is really not that surprising. 400,000 year old Iberian hominins seem to have had affinities to populations which were later found in Siberia. The Neandertals, from the Altai to Spain, seem to be surprisingly similarly and genetically homogeneous. Eurasian wolves have also gone through a population bottleneck during the Pleistocene. What this suggests to me is that the Palearctic ecozone has been characterized by a high degree of population mobility, and, extinction. Ancient DNA is sampled from northern locations due to likelihood of preservation, but these regions are also on the settlement frontier, and it wouldn’t be surprising to me that the populations are going to be characterized by low effective population sizes because they’re expanding rapidly from small founding groups.

Finally, this has some implications for our model of population assimilation and replacement. It seems that modern Europeans are a synthesis of disparate strands which have co-mingled over the past 10,000 years. One element, the majority element in the north and east, are hunter-gatherers which descend from the early West Eurasian settlers of the northwest. These were the Ice Age inhabitants of Europe. Likely they had long had connections across the latitudes of the Palearctic zone. One thing that we are seeing with the pigmentation genes is that these Western European hunter-gatherers were very different from modern Europeans. If about ~50% of the ancestry of Western Europe derives from these populations, then we’re confronted with the possibility that several of these loci have experienced nearly complete selective sweeps after an admixture event. This is not impossible, but, another option is presented us when we consider that the far north has long been a conveyor belt of peoples. Eastern cousins of the Western hunter-gatherers, could have brought whole-genome affinities into modern Europeans similar to these ancient individuals. But these may already have changed in their modal phenotype. The paper’s supplements reports that the Y chromosome of the La Brana seem to be ancient branch of haplogroup C, which is dominant in Eastern Eurasia. A possible connection to the Mal’ta people? Perhaps. But it is important to note that very low frequencies of this haplogroup still exist in Southern Europe. So the hunter-gatherers are likely not gone in toto. But combined with the mtDNA evidence of massive changes, this may point to later Bronze Age demographic shifts, being masked by the wide scope of genetic homogeneity in Eurasia.

Obviously the picture is still only partially formed. But it’s nice to have the past being painted so vividly.

Derived immune and ancestral pigmentation alleles in a 7,000-year-old Mesolithic European:

Ancient genomic sequences have started to reveal the origin and the demographic impact of farmers from the Neolithic period spreading into Europe…The adoption of farming, stock breeding and sedentary societies during the Neolithic may have resulted in adaptive changes in genes associated with immunity and diet4. However, the limited data available from earlier hunter-gatherers preclude an understanding of the selective processes associated with this crucial transition to agriculture in recent human evolution. Here we sequence an approximately 7,000-year-old Mesolithic skeleton discovered at the La Braña-Arintero site in León, Spain, to retrieve a complete pre-agricultural European human genome. Analysis of this genome in the context of other ancient samples suggests the existence of a common ancient genomic signature across western and central Eurasia from the Upper Paleolithic to the Mesolithic. The La Braña individual carries ancestral alleles in several skin pigmentation genes, suggesting that the light skin of modern Europeans was not yet ubiquitous in Mesolithic times. Moreover, we provide evidence that a significant number of derived, putatively adaptive variants associated with pathogen resistance in modern Europeans were already present in this hunter-gatherer.

The headlines about this individual having dark skin are well founded, like the Luxembourg hunter-gatherer the sample has ancestral “non-European” copies of most of the major loci which are known to have large effect sizes (SLC24A5, which is now fixed in Europeans, SLC45A2, which is present at frequencies north of 80% in most of Europe, and KITLG, a lower frequency variant known to have a major impact on skin and hair). Additionally, this individual is related to the Ma’lta individual, just like the Swedish hunter-gatherers, but unlike the Luxembourg male (which did predate the Spanish samples by 1,000 years). Lots of functional stuff is in this paper too. Seems like immune adaptations aren’t just a function of agriculture.

One thing I want to note is that I’m not sure how much of the shift toward Finns of the Swedish and Spanish hunter-gatherers is due to Paleolithic European ancestry, vs. admixture with “eastern” elements. Since the Finns seem to have more recent East Asian ancestry excess paleo-Siberian in the Mesolithic samples may shift them in the same direction. The eastward since of the La Brana individuals is really obvious in the world wide PCA, they are farther toward East Asians than any other modern Europeans.

Another huge human population genetics paper to drop soon (today?). For those who care, you can still access my Pinboard feed (it has an RSS even). Some would probably prefer it to my noisier feed.

Everyone knows that I think 23andme provides a great service. But I’ve had some criticisms in the past. Several years ago I thought it was rather strange of them to limit their chromosome painting feature to only a few ancestral components when it produced strange confusing results (e.g., many East Africans being mostly European in ancestry). Over the past few years they’ve nicely expanded their ancestry components, addressing this concern. But at this point my own inclination is to say that they’ve gone too far. For example a friend who is ethnically Japanese from Honshu gets these results: 76.1% – Japanese, 3.5% – Korean, 19.7% – Nonspecific East Asian, 0.4% – Nonspecific East Asian & Native American and 0.3% – European. I can give you reasonable explanations for these proportions, but it’s going to be confusing for many Japanese to be told they’re only 3/4 Japanese genetically. The issue is the scope of their reference population. It’s not capturing the diversity of the whole population of Japan.

But this is a minor concern in comparison to something else I’ve noticed. Here are some ancestral proportions from my family:

	French & German	British & Irish
Razib’s daughter	14.0%	8.0%
Razib’s wife	5.8%	1.6%
Razib’s father-in-law	5.2%	2.4%
Razib’s mother-in-law	3.0%	3.1%

I’ll tell you right now that I don’t have any European ancestry according to 23andMe, so my daughter’s elevated French & German and British & Irish have nothing to do with her paternal lineage. In addition I can look at the chromosome level ancestry. Most of my daughter’s chromosome 3 and all of chromosome 6 are French & German (at least the ones obviously inherited from her mother). But there is no French & German ancestry for my wife on these chromosomes (either copy). There is one recombination event from her maternal chromosome 6 and three for chromosome 3, but I don’t think that should have such a large effect.

So hypotheses? My own hunch is that clusters like French & German are somewhat artificial, insofar as they cover a very large geographic area (though granted Europe from the Bay of Biscay to the Elbe is definitely relatively genetically homogeneous). People of mixed European ancestry, like many American whites, often may resolve strangely because the methods used have a difficult time distinguishing mixed ancestry from populations which are composed of mixed ancestry (like many American whites the “French” have diverse ancestries from different regions of Europe, so many Americans may look somewhat “French”). A friend from Guatemala who is ethnically mestizo of many generations has 20% unassigned ancestry, presumably because so many recombination events have intercalated Amerindian and European segments, making it impossible for 23andMe to give a correct assignment. My parents and myself have unassigned proportions of nearly 10%, likely due to ancient admixture between our South and East Asian components, which dates back over 1,000 years in the past.

Personal genomics services are great, and I heartily recommend them. But people should be careful about taking all the results at face value. It’s like with anything else, be an informed and cautious consumer. It can be great for some things, like Dan MacArthur’s South Asian ancestry, which literally jumped out of the genetic background. But the finer you get in the grain, the more confusion will result.

Update: In the comments 23andMe scientist Eric Durand asked if I’d enabled split view. The reason he asks is that 23andMe phases the genotypes (reconstructed each physically linked segment of chromosome of the pair) before assigning ancestry along a segment. If you don’t have family information you have to use population based information. But more powerful are parental trios, since offspring simply have mixed & matched segments of their parents. And yes, I do have split view enabled, and checked it. Same weird result:

 

Greg Cochran has a few posts up on the phylogeography of SLC24A5. A quick refresher: this gene has been under very strong selection across Western Eurasia, and seems to correlate with lighter skin. One of Cochran’s points is that though it is fixed (100%) for the new variant in Europe, it persists at very high frequencies in the Middle East. Much of the sub-100% value in the Middle East can probably be attributed to recent Sub-Saharan African admixture. A paper from last fall, Molecular Phylogeography of a Human Autosomal Skin Color Locus Under Natural Selection, has convinced me that the derived variant so common across the world today probably spread from the Middle East least than 10,000 years ago. In any case, Cochran asks:

As for those who assume that sexual selection must be driving that increase – show me the time machine. I don’t know if there was any such preference over the past three thousand years in Ethiopia and neither do you. This is used as an excuse to avoid looking at the biochemical details and trying to find out what’s actually happening. If I hear it again, I may have to call the elephants.

Next, someone should do the same for the Deccan plateau, which ought to be easy.

Prompted by another paper I had stumbled upon data to answer this question a few months back. The results below are from Polymorphisms of four pigmentation genes (SLC45A2, SLC24A5, MC1R and TYRP1) among eleven endogamous populations of India (except for the HapMap samples).

Population	State	Linguistic	Status	SLC24A5	N
Konkanastha Brahmin	Maharashtra	Indo-European	Caste	0.9789	71
Gujarati	Gujarat	Indo-European	Diverse	0.955	100
Kanyakubja Brahmin	Madhya Pradesh	Indo-European	Caste	0.8846	78
Sakaldwipi Brahmin	Jharkhand	Indo-European	Caste	0.7692	65
Iyengar Brahmin	Tamil Nadu	Dravidian	Caste	0.7463	66
Mahadev	Maharashtra	Indo-European	Tribe	0.7231	65
Balmiki	Punjab	Indo-European	Caste	0.6694	62
Kurumans	Tamil Nadu	Dravidian	Tribe	0.4104	67
Gond	Madhya Pradesh	Dravidian	Tribe	0.2333	75
Riang	Tripura	Tibeto-Burman	Tribe	0.1119	67
Munda	Jharkhand	Austro-Asiatic	Tribe	0.0956	68
Tripuri	Tripura	Tibeto-Burman	Tribe	0.0923	65

If you look at the latest research it seems pretty obvious that the proportion of derived SLC24A5 in all the italicized populations is higher than their “Ancestral North Indian,” the West Eurasian element which arrived in the last 10,000 and almost certainly brought the derived variant. On the North Indian plain in Uttar Pradesh the ANI proportion for high castes like Brahmins is 60%, while for Dalit low castes like Chamars it is 40%.

The above are some commonly accepted values for the heritabilities of complex traits in the scientific literature. By heritability I mean to refer to the proportion of the variation in the trait within the population which can be explained by variation of genes within the population. The reason I am very precise is that heritability should not be taken to be some sort of obvious correlation statistic. Even though height is highly heritable in modern societies, the average sibling difference is 1.8 inches (4.6 cm). But, heritability is informative when it comes to populations and patterns of variation that we see around us. A highly heritable trait is amenable to selection for a breeder, while a non-heritable trait is not. But just because a trait is highly heritable does not mean that environment does not matter. One can imagine a scenario of “all boats rising” where environment shifts the trait value equally across the population, while all the variation within the population is still due to genes.

I’m bringing all this up because W. Bradford Wilcox has a new piece in Slate, What’s the most important factor blocking social mobility? Single parents, suggests a new study. The variable what Wilcox is alluding to in the title is illustrated in the figure to the left: the proportion of single parents in the community is very predictive. Importantly he’s arguing for very powerful community level effects. And certainly the correlation is pretty impressive. And knowing the Left’s love affair with the idea of science, he flogs this correlation rather for all that it’s worth:

Throughout his presidency, Barack Obama has stressed his commitment to data-driven decision-making, not ideology. Similarly, progressives like Krugman have stressed their scientific bona fides, as against the “anti-science” right. If progressives like the president and the Nobel laureate are serious about reviving the fortunes of the American Dream in the 21st century in light of the data, this new study suggests they will need to take pages from both left and right playbooks on matters ranging from zoning to education reform. More fundamentally, these new data indicate that any effort to revive opportunity in America must run through two arenas where government has only limited power—civil society and the American family.

The author is a visiting scholar at the Right-leaning American Enterprise Institute, but he does a good job of being evenhanded and not overtly ideological from what I have read. W. Bradford Wilcox seems to be sincerely driven by a commitment to the social issues he writes about so often. He’s also intellectually honest enough to admit that the lead author of the study which reports this stark correlation “has been careful to stress that this research cannot prove causation.”

At this point you know where I’m going with this. Wilcox admits the complexity and confounds at the heart of phenomenon he’s trying to describe. Naturally one aspect he leaves out are the innate dispositions of individuals due to their heritable makeup. More concretely, personalities differ, and those differences have consequences, and those differences partly have a genetic component. I haven’t thought about all the policy implications of this, but I do know that it makes the story that Wilcox and company tell more complicated, and likely alters the nature of the solutions that they might posit (and definitely the effect sizes they might see). Conservatives often accuse Left-liberals of being “social engineers” who neglect the complex interdependencies of organically evolved cultures. The argument is that they presume that they can model cultural outcomes as if they were as predictable as thermodynamics. But modern American conservatives have fallen into a similar trap, with the mantra “the family” “the family” “the family” as a catchall solution to all social ills. As if society is a simple pliable physical process, and the family one of its easy-to-modulate regulatory components.

It is somewhat tedious to get on this high horse over and over, but it needs to be done. Modern Left-liberals certainly won’t do it. While conservatives harp on the family, liberals focus on the economy. Ultimately both parties are missing a part of the picture, but neither is going to challenge the other on their shared lacunae.

The more we scratch beneath the surface with powerful genomic techniques, the more we see that natural history which we had presumed to have a crisp understanding of is quite a bit more muddled. Once the muddle clears what we’ll gain is the gift of accurate complexity, but in many areas right now there is little such clarity. It is a truth that a new discovery or inference does not mean that there are enough points in space to construct a new explanatory constellation when the old does not suffice. Due to the biomedical focus of modern genomics there has been a disproportionate focus on humans, but over time it is clear that this will expand out across the tree of life, and the light shall give way to a temporary fog. First up are organisms of particular human interest and/or model organisms (the latter are species which are useful for elucidating general biological phenomena, and the subjects of study of a large community of researchers). Domestic dogs have the virtue of falling into both categories.

There are many theories about the origins of our “best friend.” One school of thought (though not necessarily dominant) is that dogs are relatively recent obligate companions of humanity, part of the toolkit of the Neolithic revolution. To be fair this view was rejected by many researchers on the common sense grounds that dogs arrived with the Amerindians 10,000-15,000 years ago. These were clearly hunter-gatherer populations which predated the Neolithic. But there were some genomic research which did imply that even if there were early domestication events, the preponderance of modern domestic dog ancestry dated to the Middle East ~10,000 years before the present. The newest work in genomics seems to falsify that hypothesis rather robustly. These researchers have shown how looking closely and thoroughly at whole genomes (billions of base pairs) organisms, as opposed to a subset of polymorphisms (on the order of tens or hundreds of thousands of base pairs), can yield deeper historical insight.

A new paper out in PLOS GENETICS, Genome Sequencing Highlights the Dynamic Early History of Dogs, has been out as a preprint for a while now, but it seems useful to review what it highlights we now know, and don’t know. As illustrated by the figure above a key element of the revised natural history of the domestic dog must include a minimal level of complexity in the phylogenetic origins of the species. A caricature of the simplest story about the origin of the dog is that it is a tamed wolf. Highly derived from the ancestral state (many characteristics have shifted from the last common ancestor with wolves), but a wolf nonetheless. This idea needs updating because the work in the paper above highlights that extant wolves are not perfect representatives of Pleistocene wolf populations, from which dogs derive. This was already clear with some ancient DNA, but looking at whole genomes of three wolves from disparate regions of Eurasia, a West African Basenji, and an Australian Dingo (along with the Boxer as a reference domestic dog genome and a Golden Jack as an outgroup), a major finding seems to be that modern dogs derive from a population of wolves which are not represented in the populations sampled above. This is important because many inferences about dogs are made simply by assuming that modern wolves are appropriate proxies for the last common ancestor of both lineages.

This substitution seems to be rather shakier than we’d have thought, and this comes to play most obviously in the genetic diversity and bottleneck results we’d take for granted. If modern wolves are the standard for the ancestral population from which dogs derive then the bottleneck is a relatively mild one of a few fold drop in size (wolves are more diverse, but not that much more diverse). But what the authors above found by looking at patterns of genetic diversity across the whole genomes of these wolves is that all three, sampled from Croatia, Israel, and China, also exhibit evidence of a population bottleneck. This makes more sense of the result that it looks as if modern dog lineages underwent a population bottleneck on the order of one magnitude (16 fold). The timing using different methods also definitely predates the Neolithic revolution ~10,000 years ago, and so aligns with the archaeological evidence. Wolves were the companions of hunter-gatherers first before they were associated with farmers. Any possible adaptation of dogs to a starchy diet occurred after the initial bottleneck and separation of the ancestors of this lineage from the ancestors of modern wolves (who seem to have enough variation to have had this trait as part of the ancestral range of the trait in any case). Additionally, there are dog lineages, such as the Dingo, which don’t exhibit any adaptation to starch diets, which makes historical sense as they did not coexist with agricultural populations until recently.

I do want to caution that genomics does not change everything. Many of the broad outlines of what was known before with classical genetic techniques, comparative anatomy, and paleontology, do hold up. For example the domestic dogs do seem to form a monophyletic lineage. By this one simply means that domestic dogs the world over seem to share a small set of common ancestors, rather than being instances of convergent morphological evolution from disparate wolf lineages. What is more surprising though is that these results imply reciprocal monophyly with wolves. This means that domestic dogs are not a specialized branch of a particular population of modern wolves, but a sister lineage to contemporary wolves. Though it is common to say that a dog is just a tamed wolf, one might as easily state that a wolf is a wild dog (yes, I will grant that the dog is likely more derived, but I don’t think we can just substitute modern wolves for ancient ones and call it good). Both are subsets of a wider range of canid ancestors which flourished in the Pleistocene. The tests of admixture of particular lineages suggest that the origins of dogs seem to suggest gene flow with local wolf lineages. This would confound attempts to ascertain a particular zone of domestication or adaptation, as prior genetic affinities or clines in diversity may be due to gene flow rather than patterns of descent (earlier attempts to assert that domestic dogs derive from the Middle East or China may be premised on false assumptions, as well as limitations of less dense marker sets than whole genomes).

The main drawback of this study is obviously the limited sample size. It is freely acknowledged in the paper, but that is why the authors also attempted to select individuals from populations which were highly informative, both geographically and culturally (e.g., Dingoes are outside the range of the wolf, and, not coexistent with ancient agricultural populations). I am more skeptical about assuming that the wolf samples are representative than I am about their selection of three dog lineages (Basenji, Dingo, and the Boxer reference). We know a lot more about the genetics and history of dogs than we do about wolves, and it seems more likely that there are going to be more surprising loose ends in the case of the latter than the former. But if I had to bet I’d say the authors are right, and their inferences are going to hold up (reciprocal monophyly, the bottleneck in wolves, etc.). Yet there’s no doubt going to be a lot of detail added to this model as the sample sizes increase, and ancient DNA is is included in the analysis. Though recent studies seem to establish rather clearly that domestication was a function of the later Pleistocene (and not the Holocene) in the case of dogs, the exact details of where, when, an who, are still quite woolly.

But the ultimate big picture is emphasized by the title above: the Pleistocene is going to seem like a strange country after all is said and done. Many of the organisms which are going to be sequenced in great depth (high coverage) and large sample sizes first are mammals of Palearctic origin which were shaped by the Pleistocene. The importance of this geological period for humans has long been a subject of scholarly attention, but genomics and the light it sheds upon quirks of natural history, might emphasize the ecology-wide reshaping role that Ice Ages had upon the natural history of so many familiar and charismatic species. This is where genomics will open the door to evolutionary ecology of grand scope.

Citation: Freedman, Adam H., et al. “Genome sequencing highlights the dynamic early history of dogs.” PLoS Genetics 10.1 (2014): e1004016.

Related: Please see a post from one of the authors at Haldane’s Sieve.

I’m a pretty big fan of spicy food and hot peppers, but I’ll be honest and admit that I didn’t know much about the genomics of organisms which give rise to the flavor. So it was neat to see that Nature Genetics has an open access paper on the topic, Genome sequence of the hot pepper provides insights into the evolution of pungency in Capsicum species. Lots of new information to me in the publication. For example it seems that hot peppers have a genome on the same order of size as that of humans (and therefore most tetrapods). This is contrast to a model plant such as Arabidopsis thaliana, which is much smaller. Most of the genome consists of repetitive elements, not to surprising among eukaryotes. And the number of genes is estimated to be north of 30,000, so somewhat more than humans, but in the same range. Because peppers are Solanaceae there are excellent genomic resources to compare it with, tomato and potoato (and with nearly 200× coverage I’m assuming the assembly was OK).

The big question that they seemed to want to answer was the nature of the capsaicin biosynthesis pathway. Basically what makes peppers spicy (the posited functional reason for spiciness is that it discourages mammal consumption, but encourages birds, who are much better at scattering seeds because they fly). The conclusion the authors come to is that particular genes implicated in this function exhibit both elevated gene expression and duplication in relation to Solanaceae outgroups. This seems plausible enough, and suggests that spiciness is just a ramping up of a flavor which is present at some lower basal fraction. Why it might be useful to know which loci are implicated in spiciness is pretty obvious.

Citation: Nature Genetics (2014) doi:10.1038/ng.2877

It needs to rain in California.

Sometimes context is important when processing new information. Something huge is afoot in paleoanthropology, traditionally the study of ancient humanity predicated on analyzing morphological remains. Fossils. Though a fascinating discipline, unfortunately there’s always been an issue of supply and demand. There isn’t much supply of fossils, and there’s a lot of demand to analyze them. This means that monopoly power comes into play, as who has the fossils matters a great deal, not necessarily who has the great ideas. Some researchers have been known to sit on remains for decades. Access to particular field sites is also a precious commodity, and doled out to favorites and allies. Contrast this with the situation in modern genomics, as the swell of data is overwhelming the ability of researchers to analyze it (at least analyze it well!). Of course all of science is a human endeavor, and as such is subject to the whims of political and personal machination. But when the potential fame and glory is enormous, but resources few and far between, as is the case in paleoanthropology, the behind the scenes trench warfare can become quite brutal.

This is why what Lee Berger is doing is such a big deal. Last fall he quickly assembled a team funded by National Geographic to retrieve samples from an exceedingly rich site he happened to stumble upon. Dubbed the Rising Star Expedition the dig yielded ~1,200 remains, many of very high quality. Let that sink in. In a field where a few partial remains can reshape our whole understanding of the past, Berger is sitting on a sample size of over 1,000, many of quite high quality. But he’s not hoarding his find. Rather, he’s aiming to change the terms of how the game is played, and inviting researchers from all over the world to join him in a workshop to collaboratively analyze the results. Here’s the details of what’s going down from National Geographic:

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