The Pith: New software which gives you a more fine-grained understanding of relationships between populations and individuals.

According to the reader survey >50 percent of you don’t know how to interpret PCA or model-based (e.g., ADMIXTURE) genetic plots, so I am a little hesitant to point to this new paper in PLoS Genetics, Inference of Population Structure using Dense Haplotype Data, as it extends the results of those earlier methods. But it’s an important paper, and at some point I’ll starting using their software. The “big picture” is that earlier methods left “some information on the table.” That’s partly due to the fact that they were developed (or in the case of PCA leveraged, as it’s a very general technique) in an era where very dense marker data sets were not available (today we’re shifting to full genome sequences in many cases!). The information left on the table would be haplotype structure. Genetic variation in a concrete form manifests as sequences along a line, many of them physically connected. These correlations of nearby variant markers represent haplotypes of great interest, because they are excellent clues to admixture or divergence events across populations. In contrast the older methods, were looking at variation from marker to marker, each in turn independently, which collapses some of the important genomic structure that we can now inspect (in fact, linkage disequilibrium due to these correlations can distort some of the results in the older methods, so you want to “thin” your marker set).

Let me make this concrete for you. On 23andMe you can see where your friends shake out on a PCA plot using the HGDP data set as a reference. What this means is that the HGDP data set is used to generate independent dimensions of genetic variation. As is the usual case in these analyses the largest dimension separates Africans from everyone else, and the second largest dimension separates Asians from Europeans and Africans. 23andMe customers are then projected upon this variation, so you can get a sense where you are positioned in the clusters. To the left is a zoom in on the section for Central/South Asians. You can see that one of my friends, highlighted with a green color, falls almost perfectly in the Uygur cluster. According to ancestry estimates my friend is 50 percent Asian and 50 percent European. The “representative” Uygur in the 23andMe chromosome painting gives about the same results. But these are total genome estimates. The historical nature of my friend’s admixture and that of the Uygur woman is very different, as one can see in the below figure.

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Michelle points me to this article in The Lost Angeles Times, The Colors of the Family:

I was holding my 1-year-old, ambling about downtown with some friends. White friends. She must have thought my boy belonged to one of them.

There’s a simple explanation: I’m black but my son, Ashe, is white. At least he looks it.

But things are more complicated than that.

I’m actually half black and half white. It should come as no surprise, though, that even as sophisticated as we’ve become about people of mixed parentage, I’m pigeonholed as black. If someone asks and I don’t have time to go deeper, that’s what I call myself.

Ashe is mixed too. His mother, my wife, Vanashree, is half white and half South Asian, with roots in India. She has olive skin, and Ashe is slightly lighter than she is.

This surprised us. When Ashe was born, one of the first things I said to Vanashree was, “Honey, he’s so light!” We chuckled, poking fun at our assumptions.*

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That’s the question a commenter poses, albeit with skepticism. First, the background here. New England was a peculiar society for various demographic reasons. In the early 17th century there was a mass migration of Puritan Protestants from England to the colonies which later became New England because of their religious dissent from the manner in which the Stuart kings were changing the nature of the British Protestant church.* Famously, these colonies were themselves not aiming to allow for the flourishing of religious pluralism, with the exception of Rhode Island. New England maintained established state churches longer than other regions of the nation, down into the early decades of the 19th century.

Between 1630 and 1640 about ~20,000 English arrived on the northeastern fringe of British settlement in North America. With the rise of co-religionists to power in the mid-17th century a minority of these emigres engaged in reverse-migration. After the mid-17th century migration by and large ceased. Unlike the Southern colonies these settlements did not have the same opportunities for frontiersmen across a broad and ecological diverse hinterland, and its cultural mores were decidedly more constrained than the cosmopolitan Middle Atlantic. The growth in population in New England from the low tends of thousands to close to 1 million in the late 18th century was one of endogenous natural increase from the founding stock.

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Dienekes has an important post up, The womb of nations: how West Eurasians came to be. He outlines a scenario where a rapid expansion of a farming population has overlain much of Western Eurasia, atop aboriginal substrata. A few years ago you’d have laughed at such a model, mostly due to the authority of archaeologists and phylogeographers relying on mtDNA lineage distributions. No longer. This is not necessarily an orthodoxy, and the details of the model vary, but here is my verbal rendering of the simplest scenario:

1) ~50 thousand years hybridization between Eurasian hominins and “Out of Africa”

2) ~40-10 thousand years before the present, crystallization of the Paleolithic order of human population structure, derived from groups seeded in the original migration

3) ~10 thousand to a few thousand years before the present, the Paleolithic order is replaced and assimilated by farmers expanding from a few hearths

Below the fold is a stylized tree representation of what I have in mind.

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There’s a new paper in The American Journal of Human Genetics, Shared and Unique Components of Human Population Structure and Genome-Wide Signals of Positive Selection in South Asia. It’s free, so go read it. I don’t have time to comment in detail, but I did read the paper, and I want to mention a few things:

1) If you follow Harappa Ancestry Project or Dodecad Ancestry Project the ADMIXTURE and PCA won’t be surprising. They’ll be familiar. Though the researchers got some nice additional populations in Uttar Pradesh it didn’t change the general outlines of what you can already ascertain with the public data sets.

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The genetic model of the “Out of Africa” scenario is getting more complex. There may be two waves, as well as the likelihood of admixture between the Neo-Africans and “archaic” hominins, such the Neandertals and Denisovans. From what I can gather the genetic evidence is now converging upon the sequence of events where African populations diverge >100,000 years ago (e.g., a deep separation between the ancestors of the Bushmen and the ancestors of West Africans), and a radiation of non-Africans at most ~75,000 years ago, and more likely ~50,000 years ago. There are still many holes to be plugged in. While we’re waiting on genetics, here’s an interesting paper using archaeological methods in PLoS ONE, The Nubian Complex of Dhofar, Oman: An African Middle Stone Age Industry in Southern Arabia:

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I noticed yesterday that Andrew Sullivan, Ta-Nehisi Coates, and a cast of others were having a roiling debate on race and I.Q. My name came up in several comment threads on various issues. I’m aware of this because I have Google Alerts set for my name. I don’t have the time or energy to get immersed in this particular debate at this moment, but I did review some older material in the course of following links placed elsewhere. In particular, I encourage all of my newer readers to check out my friend Armand M. Leroi’s article in The New York Times from 2005, A Family Tree in Every Gene. Though dated in a few particulars (e.g., we know the locus responsible for most variation in blue eyes now, and it seems likely that Andaman Islanders and Malaysian Negritos are not the original settlers of their domains) I think the general outline has held up rather well. Compare it to the numerous vociferous responses over at SSRN. One wonders at the motivation for what seems like massive retaliation! Here are a few critical paragraphs from Armand’s piece:

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Slate recently had a series up on the use of mice as “model organisms.” In particular, it put the spotlight of some limitations of extrapolating from a mouse to a man (or other species). This is in some ways biology’s “WEIRD” problem. There are always going to be obvious reasons why we’d want to use mice instead of elephants as model organisms, but we might be entering into an era when the fixation on a few species might abate at least somewhat. With that, I point you to a piece in The Scientist (in its final issue I believe), Beyond the Model – How next-generation sequencing technologies will drive a new era of research on non-model organisms:

Central goals of biology have always been to understand the basis for diversity within and among species, and to understand how the environment can influence the expression of different traits. These emerging genetic approaches enable studies in a greatly expanded number of organisms and potentially allow genetic approaches to be applied in natural habitats. The use of model organisms is not dead, however. The utilization of previously generated resources and continued development of model systems will support and facilitate research in non-models. But with the ability to address molecular mechanisms in the natural world, we can truly begin to understand how all of these factors interact to generate the biological diversity that motivated the early scientists and continues to inspire us today.

There is a reason for the hype that the 21st century will be to biology what the 20th was to physics.

COMMENTS NOTE: Any comment which misrepresents the material in this post will result in banning without warning. So you should probably stick to direct quotes in lieu of reformulations of what you perceive to be my intent in your own words. For example, if you start a sentence with “so what you’re trying to say….”, you’re probably going to get banned. I said what I tried or wanted to say in the post. Period.

Genetics is powerful. The origins of the field predate Gregor Mendel, and go further back to plain human common sense. Crude theories of inheritance in the 19th century gave way in the early 20th to Mendelism, which happens to be a very powerful formal system for predicting the patterns of transmission of information from generation to generation. But I suspect that the popular accolades showered upon genetics would be more muted if it were not for the concrete discovery of the biophysical medium of that pattern of inheritance, DNA. By visualizing strands of DNA packaged into chromosomes one can gain a substantive understanding of Mendelian processes previously somewhat abstracted (e.g., recombination). In concert with the centrality of genetics at the heart of evolutionary science has been the ascendance of its methods in the older field of systematics. The phylogenetic tree is not only intuitive, but it has concrete reality in the sequences of base pairs or structural elements within the genome.

Whatever skepticism there might be about the dynamic phenomenon of evolution, the material aspect of modern genetics rooted in molecular biology is one of he primary wedges by which one can introduce an element of doubt into minds of a skeptic. The correlation between phylogeny and sequence identity of organisms which were previously adduced to exhibit some sort of biological relationship on the tree of life can not be dismissed out of hand. But this mode of thinking has limits, albeit due to the quirks of human psychology.

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I have discussed the reality that many areas of psychology are susceptible enough to false positives that the ideological preferences of the researchers come to the fore. CBC Radio contacted me after that post, and I asked them to consider that in 1960 psychologists discussed the behavior of homosexuality as if it was a pathology. Is homosexuality no longer a pathology, or have we as a society changed our definitions? In any given discipline when confronted with the specter of false positives which happen to meet statistical significance there is the natural tendency to align the outcome so that it is socially and professionally optimized. That is, the results support your own ideological preferences, and, they reinforce your own career aspirations. Publishing preferred positive results furthers both these ends, even if at the end of the day many researchers may understand on a deep level the likelihood that a specific set of published results are not robust.

This issue is not endemic to social sciences alone. I have already admitted this issue in medical sciences, where there is a lot of money at stake. But it crops up in more theoretical biology as well. In the early 20th century Charles Davenport’s research which suggested the inferiority of hybrids between human races was in keeping with the ideological preferences of the era. In our age Armand Leroi extols the beauty of hybrids, who have masked their genetic load through heterozygosity (a nations like Britain which once had a public norm against ‘mongrelization’ now promote racial intermarriage in the dominant media!). There are a priori biological rationales for both positions, hybrid breakdown and vigor (for humans from what I have heard and seen there seems to be very little evidence overall for either once you control for the deleterious consequences of inbreeding). In 1900 and in 2000 there are very different and opposing social preferences on this issue (as opposed to individual preferences). The empirical distribution of outcomes will vary in any given set of cases, so researchers are incentivized to seek the results which align well with social expectations. (here’s an example of heightened fatality due to mixing genetic backgrounds; it seems the exception rather than the rule).

Thinking about all this made me reread James F. Crow’s Unequal by nature: a geneticist’s perspective on human differences. Crow is arguably the most eminent living population geneticist (see my interview from 2006). Born in 1916, he has seen much come and go. For those of us who wonder how anyone could accept ideas which seem shocking or unbelievable today, I suspect Crow could give an answer. He was there. In any case, on an editorial note I think the essay should have been titled “Different by nature.” Inequality tends to connote a rank order of superiority or inferiority, though in the context of the essay the title is obviously accurate. Here is the most important section:

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Last of the Spanish Habsburgs

The New York Times has a long piece out, Can the Bulldog Be Saved? To a great extent it is a parable of the problems with purebred dogs. Domestic dogs are much more homozygous than humans. That is, for their two gene copies they are much more likely to exhibit similarity than humans. This is usually due to inbreeding, where a few ancestral dogs with the required traits are bred, and then selection operates upon the progeny to reduce the effective population size even more. This means that many dog breeds are in danger of pedigree collapse, where they are so inbred that going back enough generations results in a convergence of the family tree.

But the story of the bulldog isn’t just about inbreeding: it’s about correlated response. If you select upon a trait of interest, you generally produce side effects due to pleiotropy. That is, you shift the allele frequencies at locus X, which produces the outcome you want on trait 1, but also incidental outcomes on trait 2 to trait n. As stated in the piece: “Bulldogs could be as outbred as mongrel dogs in the streets of Calcutta, but if they keep that phenotype, they are not going very far.” The bulldog is profoundly unnatural in shape and gait. In other words, the issues here are not just genetic, but they’re biophysical.

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I notice that last summer Karl Smith asked “Why Are There Short People?” His logic is pretty good, except for the fact that the fitness variation seems to be much starker in males than females (there is some evidence I’ve seen that shorter women can be more fertile, though that’s balanced by the fact that larger women seem to be able to manage gestation better). In any case, height seems to be a fitness enhancing trait which is highly heritable, and yet the variation in height remains!

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Alexander Dumas, of mixed race

One of the reasons I post regularly on the genetics of mixed-race people and their physical appearance is that I don’t think the media does a good job. There’s a “freak show” element which titillates but does not illuminate. This in a period in the United States where the absolute number of people of mixed origin is increasing rapidly due to intermarriage. In fact for years I’ve gotten inquiries from the parents of mixed-race children about the scientific details of the genetics, because they are regularly questioned in depth as to how the children came to look how they look (the emails are always from women, more on that later). A relatively well written article in The New York Times illustrates some of the issues, insofar as the focus is totally on social context and dynamics, with not even a small nod to the science. The story is about a mixed-race woman (mother white and father black) who is married to a white man, whose children don’t “look black.” Specifically, her two daughters are very light-skinned, and the younger one is boldly blonde.

Here’s the jump off point of the piece:

“How come she’s so white and you’re so dark?”

The question tore through Heather Greenwood as she was about to check out at a store here one afternoon this summer. Her brown hands were pushing the shopping cart that held her babbling toddler, Noelle, all platinum curls, fair skin and ice-blue eyes.

The woman behind Mrs. Greenwood, who was white, asked once she realized, by the way they were talking, that they were mother and child. “It’s just not possible,” she charged indignantly. “You’re so…dark!”

It was not the first time someone had demanded an explanation from Mrs. Greenwood about her biological daughter, but it was among the more aggressive….

Of course it’s possible. The science behind this is trivially plain. The biological mother has alleles which code phenotypes distinctive of Europeans and Africans. Because her father is African American she is even likely to have more European ancestry than African ancestry (median African American is ~80% African and ~20% European). Genes which control variation in skin pigmentation at the scale of racial differences are distributed across half a dozen loci, but with blue vs. brown eye color there’s really only one locus which explains most (though not all) of the variation. That probably explains how both the daughters have blue eyes. The mother is probably a heteozygote, and the father is a homozygote. That means that any one of their children has a ~50% chance of having blue eyes and a ~50% chance of having brown eyes. So the chance of both daughters turning out to have blue eyes is ~25%. But obviously the science isn’t the meat of the piece. I just wish they’d given a quick explicit nod to it so that people would know why the outcome is as it is. It’s not rocket science.

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Dienekes has already commented on this, but I thought I would go over Ewen Callaway’s piece, Aboriginal genome analysis comes to grips with ethics. It’s not surprising that this was written. Even if you take Keith Windschuttle’s position when it comes to Aboriginal-European contact you can’t escape the reality that Aboriginals did not fare so well in the interaction. In fact, they don’t fare so well today in Australia. The life expectancy gap between Aboriginals and non-Aboriginals in Australia is most conservatively estimated at 10 years (do remember that the majority of indigenous Australians are mixed-race). In the racialized physical anthropology of the early 20th amongst the colored peoples Aboriginals occupied the lowest circle of hell. Because of the robustness of their physiques it was argued they were the most primitive exemplar of humanity. Perhaps relic H. erectus.

Here are some interesting sections of Callaway’s article:

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Just realized. The Science paper has some interesting dates which allows us to make the above inference.

- Separation between Europeans and East Asians 25-38 thousand years before present.

- Gene flow between proto-East Asians and proto-Australians before the Native Americans diverged from the former 15 thousand years before the present.

- A conservative first landing in Australia 40-45 thousand years before the present.

The Native American result, where they share some derived variants unique to East Eurasians (mutations which emerged after the separation from West Eurasians) with Aborigines, pegs a minimum date of admixture ~15,000 years ago. But, obviously the admixture had to occur after the divergence of West and East Eurasians. Let’s say ~30,000 years ago. Even assuming that the gene flow between East Eurasians and proto-Australians occurred immediately after the separation 38,000 ago, there were anatomically modern humans in Australia for thousands of years already! The implication is that the first Australians by necessity can not have contributed in totality the ancestry of modern Aborigines. The AJHG paper gives a 50:50 estimate for the ratio of proto-Australian and the Andaman Islander/Malaysian-Negrito related population. We don’t need to be certain of the exact value to assume that numbers like this imply considerable admixture above trace levels.

Of all the dates I’m probably most confident about the archaeological ones about the settlement of Australia by anatomically modern humans. 46,000 years ago the megafauna started going extinct. That’s an immediate tell that humans have been let into the garden.