Jerry Coyne on race: a reflection of evolution

After my post on the ‘race question’ I thought it would be useful to point to Jerry Coyne’s ‘Are there human races’?. The utility is that Coyne’s book Speciation strongly shaped my own perceptions. I knew the empirical reality of clustering before I read that book, but the analogy with “species concept” debates was only striking after becoming more familiar with that literature. Coyne’s post was triggered by a review of Race?: Debunking a Scientific Myth and Race and the Genetic Revolution: Science, Myth, and Culture. He terms the review tendentious, and I generally agree.

In the early 20th century Western intellectuals of all political stripes understood what biology told us about human taxonomy. In short, human races were different, and the white European race was superior on the metrics which mattered (this was even true of Left-Socialist intellectuals such as H. G. Wells and Jack London). In the early 21st century Western intellectuals of all political stripes understand what biology teaches us about human taxonomy. Human races are basically the same, and for all practical purposes identical, and equal on measures which matter (again, to Western intellectuals). As Coyne alludes to in his post these are both ideologically driven positions. One of the main reasons that I shy away from modern liberalism is a strong commitment to interchangeability and identity across all individuals and populations as a matter of fact, rather than equality as a matter of legal commitment. In a minimal government scenario the details of human variation are not of particular relevance, but if you accept the feasibility of social engineering (a term I am not using in an insulting sense, but in a descriptive one) you have to start out with a model of human nature. So this is not just an abstract issue. For whatever reason many moderns, both liberals and economic conservatives, start out with one of near identity (e.g., H. economicus in economics).

I want to highlight a few sections of Coyne’s post:

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Are Sardinians like Iberians?

Dienekes asks:

In terms of autosomal DNA, the Iceman clearly clusters with modern Sardinians, and also appears slightly more removed than them compared to continental Europeans. Interestingly, at least as far as the PC analyssi shows, Sardinians appear to be intermediate between the Iceman and SW Europeans, rather than Italians. Perhaps, this makes sense if the Paleo-Sardinian language is indeed related to languages of Iberia.

This trend aroused a little curiosity in me too. I’m sure Dienekes & company will be probing these issues a lot in the near future, but I couldn’t wait. I took the IBS data set, which includes a lot of individuals from various areas of Spain, the Sardinians, French and French Basque from the HGDP, and the Tuscans from the HapMap, and threw them together into a pot. I added HGDP Russians & Orcadians (the latter a British group) to make sure there was a North European “outgroup.” In terms of technical details the combined data set had ~220,000 SNPs, not too shabby. Additionally, I decided to run a PCA, where this number of SNPs is more than sufficient.

On a technical note, the Sardinians were swamped in raw numbers by Iberians and Tuscans (over 100 and around 80 respectively). This means that the peculiarities of the Sardinian genetic heritage didn’t show up, rather, what you see are the Sardinians as they arrange themselves in relation to the genetic variation of these more numerous groups. I used SmartPCA to generate the 10 largest independent dimensions of variation. To make a long story short there really wasn’t much variation added from the second dimension on in this relatively homogeneous sample. So below is PC 1 and 2 (E1 and E2).

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Ötzi the Iceman and the Sardinians

Well, the paper is finally out, New insights into the Tyrolean Iceman’s origin and phenotype as inferred by whole-genome sequencing. In case you don’t know, Ötzi the Iceman died 5,300 years ago in the alpine region bordering Austria and Italy. His seems to have been killed. And due to various coincidences his body was also very well preserved. This means that enough tissue remained that researchers have been able to amplify his DNA. And now they’ve sequenced it enough to the point where they can make some inferences about his phenotypic characteristics, and, his phylogenetic relationships to modern populations.

The guts of this paper will not be particularly surprising to close readers of this weblog. The guesses of some readers based on what the researchers hinted were correct: Ötzi seems to resemble mostly closely the people of Sardinia. This is rather interesting. One reason is prosaic. The HGDP sample used in the paper has many Northern Italians (from Bergamo). Why is it that Ötzi does not resemble the people from the region that he was indigenous to? (we know that he was indigenous because of the ratio of isotopes in his body) A more abstruse issue is that it is interesting that Sardinians have remained moored to their genetic past, enough so that a 5,300 year old individual clearly can exhibit affinities with them. The distinctiveness of Sardinians jumps out at you when you analyze genetic data sets. They were clearly set apart in L. L. Cavalli-Sforza’s The History and Geography of Human Genes, 20 years ago. One reason that Sardinians may be distinctive is that Sardinia is an isolated island. Islands experience reduced gene flow because they’re surrounded by water. And sure enough, Sardinians are especially similar to each other in relation to other European populations.

 

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Nerves of a feather, wire together

Finding your soulmate, for a neuron, is a daunting task. With so many opportunities for casual hook-ups, how do you know when you find “the one”?

In the early 1960’s Roger Sperry proposed his famous “chemoaffinity theory” to explain how neural connectivity arises. This was based on observations of remarkable specificity in the projections of nerves regenerating from the eye of frogs to their targets in the brain. His first version of this theory proposed that each neuron found its target by expression of matching labels on their respective surfaces. He quickly realised, however, that with ~200,000 neurons in the retina, the genome was not large enough to encode separate connectivity molecules for each one. This led him to the insight that a regular array of connections of one field of neurons (like the retina) across a target field (the optic tectum in this case) could be readily achieved by gradients of only one or a few molecules.

The molecules in question, Ephrins and Eph receptors, were discovered thirty-some years later. They are now known to control topographic projections of sets of neurons to other sets of neurons across many areas of the brain, such that nearest-neighbour relationships are maintained (e.g., neurons next to each other in the retina connect to neurons next to each other in the tectum). In this way, the map of the visual world that is generated in the retina is transmitted intact to its targets. Actually, maintenance of nearest-neighbour topography seems to be a general property of projections between any two areas, even ones that do not obviously map some external property across them.

But the idea of matching labels was not wrong – they do exist and they play a very important part in an earlier step of wiring – finding the correct target region in the first place. This is nicely illustrated by a beautiful paper studying projections of retinal neurons in the mouse, which implicates proteins in the Cadherin family in this process.

In the retina, photoreceptor cells sense light and transmit this information, through a couple of relays, to retinal ganglion cells (RGCs). These are the cells that send their projections out of the retina, through the optic nerve, to the brain. But the tectum is not the only target of these neurons. There are, in fact, at least 20 different types of RGCs with distinct functions that project from the retina to various parts of the brain.

In mammals, “seeing” is mediated by projections to the visual centre of the thalamus, which projects in turn to the primary visual cortex. But conscious vision is only one thing we use our eyes for. The equivalent of the tectum, called the superior colliculus in mammals, is also a target for RGCs, and mediates reflexive eye movements, head turns and shifts of attention. (It might even be responsible for blindsight – subconscious visual responsiveness in consciously blind patients). Other RGCs send messages to regions controlling circadian rhythms (the suprachiasmatic nuclei) or pupillary reflexes (areas of the midbrain called the olivary pretectal nuclei).

These RGCs express a photoresponsive pigment (melanopsin) and respond to light directly. This likely reflects the fact that early eyes contained both ciliated photoreceptors (like current rods and cones) and rhabdomeric photoreceptors (possibly the ancestors of RGCs and other retinal cells).

So how do these various RGCs know which part of the brain to project to? This was the question investigated by Andrew Huberman and colleagues, who looked for inspiration to the fly eye. It had previously been shown that a member of the Cadherin family of proteins was involved in fly photoreceptor axons choosing the right layer to project to in the optic lobe. Cadherins are “homophilic” adhesion molecules – they are expressed on the surface of cells and like to bind to themselves. Two cells expressing the same Cadherin protein will therefore stick to each other. This stickiness may be used as a signal to make a synaptic connection between a neuron and its target.

The protein implicated in flies, N-Cadherin, is widely expressed in mammals and thus unlikely to specify connections to different targets of the retina. But Cadherins comprise a large family of proteins, suggesting that other members might play more specific roles. This turns out to be the case – a screen of these proteins revealed several expressed in distinct regions of the brain receiving inputs from subtypes of RGCs. One in particular, Cadherin-6, is expressed in non-image-forming brain regions that receive retinal inputs – those controlling eye movements and pupillary reflexes, for example. The protein is also expressed in a very discrete subset of RGCs – specifically those that project to the Cadherin-6-expressing targets in the brain.

The obvious hypothesis was that this matching protein expression allowed those RGCs to recognise their correct targets by literally sticking to them. To test this, they analysed these projections in mice lacking the Cadherin-6 molecule. Sure enough, the projections to those targets were severely affected – the axons spread out over the general area of the brain but failed to zero in on the specific subregions that they normally targeted.

These results illustrate a general principle likely to be repeated using different Cadherins in different RGC subsets and also in other parts of the brain. Indeed, a paper published at the same time shows that Cadherin-9 may play a similar function in the developing hippocampus. In addition, other families of molecules, such as Leucine-Rich Repeat proteins may play a similar role as synaptic matchmakers by promoting homophilic adhesion between neurons and their targets. (Both Cadherins and LRR proteins also have important “heterophilic” interactions with other proteins).

The expansion of these families in vertebrates could conceivably be linked to the greater complexity of the nervous system, which presumably requires more such labels to specify it. But these molecules may be of more than just academic interest in understanding the molecular logic and evolution of the genetic program that specifies brain wiring. Mutations in various members of the Cadherin (and related protocadherin) and LRR gene families have also been implicated in neurodevelopmental disorders, including autism, schizophrenia, Tourette’s syndrome and others. Defining the molecules and mechanisms involved in normal development may thus be crucial to understanding the roots of neurodevelopmental disease.

Osterhout, J., Josten, N., Yamada, J., Pan, F., Wu, S., Nguyen, P., Panagiotakos, G., Inoue, Y., Egusa, S., Volgyi, B., Inoue, T., Bloomfield, S., Barres, B., Berson, D., Feldheim, D., & Huberman, A. (2011). Cadherin-6 Mediates Axon-Target Matching in a Non-Image-Forming Visual Circuit Neuron, 71 (4), 632-639 DOI: 10.1016/j.neuron.2011.07.006

Williams, M., Wilke, S., Daggett, A., Davis, E., Otto, S., Ravi, D., Ripley, B., Bushong, E., Ellisman, M., Klein, G., & Ghosh, A. (2011). Cadherin-9 Regulates Synapse-Specific Differentiation in the Developing Hippocampus Neuron, 71 (4), 640-655 DOI: 10.1016/j.neuron.2011.06.019

Neandertal population structure

There’s a new paper out, Partial genetic turnover in neandertals: continuity in the east and population replacement in the west. The primary results are above. Basically, using 13 mtDNA samples the authors conclude that it looks as if there was a founder effect for Neanderthals in Western Europe ~50 K years ago, generating a very homogenized genetic background for this particular population before the arrival of modern humans. Perhaps it’s just me, but press releases with headlines such as “European Neanderthals Were On the Verge of Extinction Even Before the Arrival of Modern Humans” strike me as hyperbolic. I’m also confused by quotes like the one below:

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Men on the move and women in place?

After posting on Basque mtDNA I wanted to make something more explicit that I alluded to below, that uniparental lineages are highly informative, but they may not be representative of total genome content. This is plainly true in the case of mestizos from Latin America, but we don’t need genetics to point us in the right direction on this score, we have plenty of textual evidence for asymmetry in sexes when it came to admixture events in the post-Columbian era. Rather, I want to note again the issue of South Asia. When it comes to mtDNA the good majority of South Asian lineages are closer to those of East Asia than Western Eurasia. By this, I do not mean to say that that they’re particular close to East Asian lineages, only that if you go back in the phylogeny the South Asian lineages (I’m thinking here of haplogroup M) they tend to coalesce first with East Asian lineages before they do so with West Eurasian lineages.

Here is a quote from one of the definitive papers on this topic:

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Parkinson’s disease patients & free 23andMe

Michelle tipped me off to 23andMe’s new initiative to get Parkison’s disease sufferers genotyped. Basically, if you are a sufferer, you get the service for free. The goal presumably to increase the sample size so as to pick up new possible associations. But a question: can you think of a downside for Parkinson’s disease sufferers? A lot of people have genetic privacy concerns, but if you manifest a disease like Parkinson’s I suspect that’s the least of your worries.

Basque maternal heritage & continuity

There’s a new paper in AJHG which caught my eye, The Basque Paradigm: Genetic Evidence of a Maternal Continuity in the Franco-Cantabrian Region since Pre-Neolithic Times (ungated). The first thing you need to know about this paper is that it focuses on only the direct maternal lineage of Basques via the mtDNA. In some ways this is weak tea, since it doesn’t give us a total genome estimate. But there are major upsides to mtDNA and Y. First, because of the lack of recombination it is relatively easy to generate a nice phylogenetic tree using a coalescent model. And second, for mtDNA the molecular clock is considered relatively reliable.

In this specific paper they also expanded the scope of their analysis to the whole mtDNA sequence, instead of just the hypervariable region. Not only did they look at whole sequences, but they also had an enormous sample size. They sequenced over 400 mtDNA genomes from the Basque country and neighboring regions. Haplogroup H peaks in frequency among Basques, and drops off among their neighbors (Gascons, Spaniards, etc.). Because the Basque speak a non-Indo-European language they are usually presumed to be indigenous in relation to their neighbors (or at least more indigenous). Until recently there was a strong presupposition that the Basque were ideal representatives of the pre-Neolithic populations of Western Europe. One common method of analysis would be to use the Basque as a pre-Neolithic “reference,” and simply estimate the impact of a Neolithic demographic wave of advance by using a eastern Mediterranean population as a second “reference” within an admixture framework. But more recent work has muddled the idea that the Basque are the descendants of Paleolithic Europeans. Finally, I suspect we’ll also have to acknowledge complexity in demographic histories. To say that the Basque exhibit continuity with Mesolithic Iberians may not contradict a substantial Neolithic contribution. South Asians for example are one numerous modern group which exhibits sharply divergent affinities if you use Y chromosomes (West Eurasian) or mtDNA (not West Eurasian). Why? The details are prehistorical.

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The data sets in the dark

Recently I was tipped off to the appearance of a new paper, Genome-Wide Association Study Identifies Chromosome 10q24.32 Variants Associated with Arsenic Metabolism and Toxicity Phenotypes in Bangladesh. This is the section which caught my eye: “Using data on urinary arsenic metabolite concentrations and approximately 300,000 genome-wide single nucleotide polymorphisms (SNPs) for 1,313 arsenic-exposed Bangladeshi individuals.” 300 K SNPs with 1,313 Bangladeshi individuals is a lot! I’m interested in this data set because of the 200+ participants in the Harappa Ancestry Project my parents remain the “unadmixed” South Asians with the highest fraction of East Asian ancestry (10-15 percent). Within South Asia aside from those groups with clear East Asian affinities only peoples of Munda background have the same levels. This data set could answer a lot of questions as to the typicality of my parents (literally within a few hours in terms of data exploration). But this is all you get in the supplements:

 

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How common are godless liberals?

 

I’m going to be speaking at the Moving Secularism Forward conference in Orlando next week. They invited me because I’m a conservative atheist public intellectual, and the three other conservative atheist public intellectuals in the United States were presumably busy. In any case, going over what I’m going to talk about I was double-checking political breakdowns by atheist & agnostic proportions and ideology in the General Social Survey for after the year 2000.

I used the “GOD” variable, which asks people about their belief in God. Those who did not believe, or said there was no way to find out, I classed as “atheists & agnostics.” This means that the total percentages in the population are higher than self-reports; that’s because the word atheism in particular has a negative connotation (I recall that Julia Sweeney’s parents were tolerant of the fact that she did not believe in God, but were aghast that she was an atheist!). “POLVIEWS” what the variable which I crossed “GOD” with. It has seven responses, from very liberal to very conservative, and I just put all liberals and conservatives into one category.

The first table displays what proportion in the whole society atheist & agnostic liberals (or conservatives) are. Since the total proportion of atheists & agnostics is small, naturally these percentages are small. The two subsequent tables just display what percentage of atheists & agnostics are liberal, or what percentage of liberals are atheist & agnostic.

 

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