Last weekend I mentioned a paper, The Genetic Structure and History of Africans and African Americans, which had the best coverage of disparate African populations we’ve seen so far. The map to the left shows the various ancestral population clusters inferred from the samples they had. Really the only failing is that they didn’t have samples from Angola, Zambia, Zimbabwe and Mozambique. Unfortunately, that’s not totally trivial. These are regions which were effected by the Bantu Expansion, with southern Angola in particular still having remnants of Khoisan language speakers which likely attest to the pre-Bantu populations. Luckily for us innovation and scientific ingenuity are such that minor questions can quickly be answered because of how cheap the basic methods have become. A new paper in The European Journal of Human Genetics tackles Mozambique in particular, and discerns a heretofore unknown possible population cluster. A genomic analysis identifies a novel component in the genetic structure of sub-Saharan African populations:

Studies of large sets of single nucleotide polymorphism (SNP) data have proven to be a powerful tool in the analysis of the genetic structure of human populations. In this work, we analyze genotyping data for 2841 SNPs in 12 sub-Saharan African populations, including a previously unsampled region of southeastern Africa (Mozambique). We show that robust results in a world-wide perspective can be obtained when analyzing only 1000 SNPs. Our main results both confirm the results of previous studies, and show new and interesting features in sub-Saharan African genetic complexity. There is a strong differentiation of Nilo-Saharans, much beyond what would be expected by geography. Hunter-gatherer populations (Khoisan and Pygmies) show a clear distinctiveness with very intrinsic Pygmy (and not only Khoisan) genetic features. Populations of the West Africa present an unexpected similarity among them, possibly the result of a population expansion. Finally, we find a strong differentiation of the southeastern Bantu population from Mozambique, which suggests an assimilation of a pre-Bantu substrate by Bantu speakers in the region.

The main value-add of the research were the 279 individuals from Mozambique, who they plugged into previous data sets (e.g., HGDP, HapMap3). It must also be noted that they limited their genetic survey to ~2800 SNPs.This is sufficient for their purposes. Below are the figures of interest from the paper. Note immediately how Mozambique separates out at K = 4 in the first image. The subsequent figures are from PCA. The axes represent components of variation. The last panel shows a PCA plot transposed onto a map. In this case, PC 1 & PC3.t

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STRUCTURE

PC1 & PC2

PC1 & PC3

PC1 & PC3 on map

The first figure is important because it suggests population structure we hadn’t known of in the Bantu Expansion. This doesn’t mean that it should be surprising. With Africa’s current level of genetic variation it seems implausible that the carriers of the Bantu culture would not have assimilated other groups along the wave of advance. In fact, as a cultural movement gains steam through positive feedback loops different societies may become co-opted into them, and spread the culture in their own turn. As an American example, I will give the Irish American Catholic hierarchy’s campaigns against German language parochial school instruction in the 19th century. Old English aside the language of the Irish was originally not English, but by the early 19th century apparently English had already become dominant among the Roman Catholic peasantry of Ireland. So they brought English, not Gaelic, to the United States. Similarly, the spread of Islam in India occurred predominantly under the ageis of Turks and Afghans, not Arabs, while the spread of Islam in Southeast Asia was promoted by South Asian Muslim merchants in their turn. So you have Arab cultural forms in eastern Indonesia thanks to cultural expansions at two removes from the original Arab source (in fact, it could be argued that the Turks and Afghans were Islamicized through a Persian intermediate as well).

But it is the PCA plots which are of more curiosity for me. They note that it is the third component of variation which maps well onto geographic distance. In the paper they say:

This is the PC that is mostly correlated with geography…and the fact that it is the third rather than the first component, as would be expected if isolation by distance was the predominant force shaping genetic diversity…implies that directional population movements (such as the Bantu expansion) and barriers to gene flow (such as that between food producers and hunter gatherers) are more relevant than geographic distance to understand the genetic landscape of sub-Saharan Africa….

There were folk migrations in Africa. They might simply not have been the ones we are aware of, at least in our sparest conceptions. Those folk migrations were very recent, within the last ~2,000 years or so. Which is why the distinctive correlations between language and genes persist, especially on the outer edge of the wave of advance in southern Africa (in contrast, the Pygmies of the Congo have lost their native language, and the western Pygmies are highly admixed with their neighbors).

Citation: A genomic analysis identifies a novel component in the genetic structure of sub-Saharan African populations

Addendum: The life of Shaka may give us a clue as the disturbances which pushed the Bantu ever outward.

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Over the past decade evolutionary geneticist Mike Lynch has been articulating a model of genome complexity which relies on stochastic factors as the primary motive force by which genome size increases. The argument is articulated in a 2003 paper, and further elaborated in his book The Origins of Genome Architecture. There are several moving parts in the thesis, some of which require a rather fine-grained understanding of the biophysical structural complexity of the genome, the nature of Mendelian inheritance as a process, and finally, population genetics. But the core of the model is simple: there is an inverse relationship between long term effective population size and genome complexity. Low individual numbers ~ large values in terms of base pairs and counts of genetic elements such as introns.

A quick reminder: effective population size denotes the proportion of the population which contributes genes to the next generation. So, in the case of insects with extremely high mortality in the larval stage the effective population size may be orders of magnitude smaller than the census size at any given generation evaluating over all stages of life history. In contrast, with humans a much larger proportion of children end up contributing to the genetic makeup of the subsequent generation. With large organisms I’ve heard you can sometimes use a rule of thumb that effective population size is ~1/3 of census size, though this probably overestimates the effective population size. One reason that reproductive variation reduces the effective population, because many individuals contribute far less to the next generation than other individuals. The greater the variance, the more evolutionary genetic variation is impacted by a few individuals within the population at a given generation, reducing effective population which contributes to the next (the reproductive variance is often assumed to be poisson, but that is likely an underestimate). Additionally, there is the issue of variation over time. Long term effective population is much more sensitive to low bound values than high bound values, so it is liable to be much smaller than the census size at any given period for a species which goes through cycles. Humans for example have a relatively small long term effective population size evaluated over the past 100,000 years because we seem to have expanded from a small initial population. Mathematically since long term effective population size is given by the harmonic mean it stands to reason that low bound values would be critical. If that doesn’t make sense to you, remember the outsized impact which population bottlenecks may have on the long term trajectory of a species, in particular by removing genetic variation.

How does this influence genome complexity? Basically Lynch’s thesis is that when you reduce effective population you dampen the power of natural selection, specifically purifying selection, from preventing the addition of non-adaptive complexity through random processes. It isn’t that selection is rendered moot, rather, its signal is overwhelmed by the noise. Here’s the abstract of his 2003 paper:

Complete genomic sequences from diverse phylogenetic lineages reveal notable increases in genome complexity from prokaryotes to multicellular eukaryotes. The changes include gradual increases in gene number, resulting from the retention of duplicate genes, and more abrupt increases in the abundance of spliceosomal introns and mobile genetic elements. We argue that many of these modifications emerged passively in response to the long-term population-size reductions that accompanied increases in organism size. According to this model, much of the restructuring of eukaryotic genomes was initiated by nonadaptive processes, and this in turn provided novel substrates for the secondary evolution of phenotypic complexity by natural selection. The enormous long-term effective population sizes of prokaryotes may impose a substantial barrier to the evolution of complex genomes and morphologies.

The implication here is that prokaryotes with massive population sizes are biased toward smaller genomes by the more efficacious application natural selection. In contrast, more complex organisms which have smaller population sizes, and so are more impacted by the random fluctuations generation to generation due to sample variance, are less streamlined genomically because selection can do only so much against the swelling sea of noise. One intriguing argument of Lynch is that the genomic complexity is then later useful downstream as the building block of phenotypic complexity, but let’s set that aside for now.

A new paper in PLoS Genetics challenges the statistical analysis of the original data which Lynch et al. used to make their case. Technically the argue was that there was an inverse relationship between N_eu and genome size. N_e is effective population size, and u is nucleotide mutation rate. Though argument is technical, and the basic objection should be easy to understand: there are other variables which may actually be responsible for the correlation which Lynch et al. discerned. To the paper, Did Genetic Drift Drive Increases in Genome Complexity?:

Genome size (the amount of nuclear DNA) varies tremendously across organisms but is not necessarily correlated with organismal complexity. For example, genome sizes just within the grasses vary nearly 20-fold, but large-genomed grass species are not obviously more complex in terms of morphology or physiology than are the small-genomed species. Recent explanations for genome size variation have instead been dominated by the idea that population size determines genome size: mutations that increase genome size are expected to drift to fixation in species with small populations, but such mutations would be eliminated in species with large populations where natural selection operates at higher efficiency. However, inferences from previous analyses are limited because they fail to recognize that species share evolutionary histories and thus are not necessarily statistically independent. Our analysis takes a phylogenetic perspective and, contrary to previous studies, finds no evidence that genome size or any of its components (e.g., transposon number, intron number) are related to population size. We suggest that genome size evolution is unlikely to be neatly explained by a single factor such as population size.

In the original analysis by Lynch et al. ~66% of the variation in genome size was explained by N_eu! That’s a pretty large effect. Figure 1 illustrates how phylogeny could be a confound in adducing a relationship. Here’s some of the text which explains the figure:

In this hypothetical example, eight species have been measured for two traits, x and y, as indicated by pairs of values at the tips of the phylogenetic tree (A). Ordinary least-squares linear regression (OLS) indicates a statistically significant positive relationship (B; r-squared = 0.62, P = 0.02), potentially leading to an inference of a positive evolutionary association between x and y. However, inspection of the scatterplot (B) in relation to the phylogenetic relationships of the species (A) indicates that the association between x and y is negative for the four species within each of the two major lineages. Regression through the origin with phylogenetically independent contrasts…which is equivalent to phylogenetic generalized least squares (PGLS) analysis, accounts for the nonindependence of species and indicates no overall evolutionary relationship between the traits…The apparent pattern across species was driven by positively correlated trait change only at the basal split of the phylogeny; throughout the rest of the phylogeny, the traits mostly changed in opposite directions (A; basal contrast in red)….

The argument then seems to be that the relationship in the original work by Lynch was an artifact due to the evolutionary history of the species which he surveyed to infer the relationship. Instead of a general principle or law then what you have is an outcome of contingent historical processes. Not very neat and clean. You can see the taxa-clustered nature of the relationship in figure 1 from the 2003 paper in Science:

OK, now let’s look at the visualization of the same data set from this paper, as a tree to illustrate the correlations:

The last figure shows the difference between a scatterplot using conventional OLS regression, and the phylogenetic least squares model (PGLS). You go from an obvious linear relationship, which translated into the high r-squared noted above, to basically nothing (r-squared near zero, no statistical significance).

The paper itself isn’t that long, the objection is pretty straightforward. They’re simply claiming that Lynch didn’t correct for an obvious alternative explanation/confound, and that we don’t know what we thought we knew. Additionally, there is the assertion that the idea that effective population size predicts genome size robustly is becoming conventional wisdom within the scientific community. I don’t know about that, this seems like such a young field in flux that I think they oversold how widespread this assumption is to make the force of their rebuttal more critical. Certainly the patterns in genome size can be quite perplexing, but my intuition is that an r-squared on the order of 2/3 of the variation in genome size being explained by one predictor variable is rather astounding. Obviously genome size is pretty easy to get in the “post-genomic era,” but N_e and u are harder to come by for many taxa, or even within a given taxon for a set of species of interest. It looks to me an opportunity for experimental evolutionalists, who can control the confounds, and observe changes within a lineage. And yet even if N_eu is predictive as an independent variable all things controlled, what if all things are not usually controlled, and random acts of phylogenetic history are more important? Mike Lynch is credited in the acknowledgements, so I assume we’ll be seeing a response from him in the near future.

Citation: Whitney KD, & Garland T Jr (2010). Did Genetic Drift Drive Increases in Genome Complexity? PLoS Genetics : 10.1371/journal.pgen.1001080

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Last spring two very thorough papers came out which surveyed the genetic landscape of the Jewish people (my posts, Genetics & the Jews it’s still complicated, Genetics & the Jews). The novelty of the results was due to the fact that the research groups actually looked across the very diverse populations of the Diaspora, from Morocco, Eastern Europe, Ethiopia, to Iran. They constructed a broader framework in which we can understand how these populations came to be, and how they relate to each other. Additionally, they allow us to have more perspective as to the generalizability of medical genetics findings in the area of “Jewish diseases,” which for various reasons usually are actually findings for Ashkenazi Jews (the overwhelming majority of Jews outside of Israel, but only about half of Israeli Jews).

Just as the two aforementioned papers were deep explorations of the genetic history of the Jewish people, and allowed for a systematic understanding of their current relationships, a new paper in PNAS takes a slightly different tack. First, it zooms in on Ashkenazi Jews. The Jews whose ancestors are from the broad swath of Central Europe, and later expanded into Poland-Lithuania and Russia. The descendants of Litvaks, Galicians, and the assimilated Jewish minorities such as the Germans Jews. Second, though constrained to a narrower population set, the researchers put more of an emphasis on the evolutionary parameter of natural selection. Like any population Jews have been impacted by drift, selection, migration (and its variant admixture), and mutation. Teasing apart these disparate parameters may aid in understanding the origin of Jewish diseases.

The paper is open access, so you don’t have to take my interpretation as the last word. Signatures of founder effects, admixture, and selection in the Ashkenazi Jewish population:

The Ashkenazi Jewish (AJ) population has long been viewed as a genetic isolate, yet it is still unclear how population bottlenecks, admixture, or positive selection contribute to its genetic structure. Here we analyzed a large AJ cohort and found higher linkage disequilibrium (LD) and identity-by-descent relative to Europeans, as expected for an isolate. However, paradoxically we also found higher genetic diversity, a sign of an older or more admixed population but not of a long-term isolate. Recent reports have reaffirmed that the AJ population has a common Middle Eastern origin with other Jewish Diaspora populations, but also suggest that the AJ population, compared with other Jews, has had the most European admixture. Our analysis indeed revealed higher European admixture than predicted from previous Y-chromosome analyses. Moreover, we also show that admixture directly correlates with high LD, suggesting that admixture has increased both genetic diversity and LD in the AJ population. Additionally, we applied extended haplotype tests to determine whether positive selection can account for the level of AJ-prevalent diseases. We identified genomic regions under selection that account for lactose and alcohol tolerance, and although we found evidence for positive selection at some AJ-prevalent disease loci, the higher incidence of the majority of these diseases is likely the result of genetic drift following a bottleneck. Thus, the AJ population shows evidence of past founding events; however, admixture and selection have also strongly influenced its current genetic makeup.

The sample size of Ashkenazi Jews was ~400, and they looked at ~700,000 SNPs. As I said, how Jews relate to other populations really isn’t at the core of this paper as it was in the earlier ones from the spring, but there were the PCA plots (sorry Mike), a frappe bar plot, and a phylogenetic tree derived from Fst statistic. Again, remember that PCA is showing you the largest independent components of genetic variation within the data. The bar plot has a set of ancestral populations of which individuals are composites of. And finally, Fst measures between population component of genetic variation. The larger the Fst across two populations the bigger the genetic distance.

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PCA + frappe

PCA with labels

Fst & tree

Using the Druze & Palestinians as the ancestral Middle Eastern reference the authors estimated that the European admixture into Ashkenazi Jews is on the order of 30-55%. This is in the same ballpark as the previous studies, so no great surprise. As I stated in earlier posts the authors can spin the same results in very different ways. From what I can tell these authors are inclined to emphasize the strong possibility that in terms of genetic distance Ashkenazi Jews are somewhat closer to Europeans than they are to Levantine Arabs. Of course these sorts of assertions need to be handled with care. The genetic distance between Ashkenazi Jews and Tuscans is less than half that between Ashenazi Jews and Russians, while the Jewish-Russian value is about 50% larger than the Jewish-Palestinian one. Remember that there’s a fair amount of circumstantial evidence that Tuscans may themselves be a relatively recent hybrid population between indigenous residents of the Italian peninsula and Near Easterners.

One thing that this paper does do is rebut any strong assertion that Ashkenazi Jews are a genetically homogeneous population which went through a powerful bottleneck. Basically, the idea that Jewish diseases are just an outcome of the operational inbreeding that occurs when genetic variation is expunged from a population through low effective population size. The clincher seems to be comparison of heterozygosity of Ashkenazi Jews and gentile Europeans. The former are actually somewhat more heterozygous than the latter. There’s been a bit of evidence from previous research that the long term effective population size of Ashkenazi Jews was not necessarily very small, so this isn’t a total surprise. Remember that heterozygosity simply means the fraction of individuals heterozygous at a locus.

One way you can become heterozygous is naturally admixture. Remember that populations differ across many genes. As an example, there’s a pigmentation gene, SLC24A5, where all Europeans are at one state, and all West Africans in another. Naturally African Americans exhibit much more heterozygosity on this locus than the ancestral populations. The Ashkenazi Jewish case is less extreme because the two parental populations are genetically closer, but the principle still holds.

A consequence of recent admixture between genetically different populations are high levels of linkage disequilibrium, non-random associations of alleles at different loci across the genome. Why? There are many genes where two populations may be very different. Offspring inherit half their genome from one parent, and half from the other, and the parents pass along to their offspring particular associations of alleles. There may be a set of European distinctive alleles on a chromosome, and an African distinctive set of alleles, so that in a hybrid individual the alleles are strongly correlated across loci. These associations are broken down over time by recombination. The regularity of this process can serve as a clock with which to measure the period since admixture. African Americans were used to calibrate the time since admixture for the Uyghur people of western China, who are mixed from West and East Eurasian populations. The authors did not do this in this paper, I assume because the ancestral populations were genetically rather close in comparison to the two above examples, so there’d be less linkage disequilibrium to break down in the first place.

In the Ashkenazi Jewish population they found more linkage disequilibrium than in Europeans as well as longer haplotypes. This could be the result of a population bottleneck where drift could drive up the frequency of blocks of the genome, but as they note in the paper that should probably reduce heterozygosity. The natural inference then is that admixture between distinct populations can explain both data points.

But let’s cut to the chase. What genes exhibit signatures of natural selection in Ashkenazi Jews? More precisely, what distinctive regions of the genome exhibit signatures of natural selection? They used the standard haplotype type based methods. Basically you’re looking for regions of the genome where there are long blocks of correlated alleles, signs of a selective sweep due to a favored variant which dragged along flanking genomic regions as it rose rapidly in frequency, more rapidly than recombination could break apart the associations. Because recombination does breaks up associations over time, you need the selective sweeps to be relatively recent to detect them with these methods. Since the Jewish people, and Ashkenazi Jews more particularly, are relatively recent historically timing shouldn’t be an issue for Jewish specific sweeps. But another factor is that the two primary tests they used, EHH and iHS, are not good at picking up sweeps which are just starting. EHH is geared toward sweeps which are almost complete, so the frequency of the selected allele is near 100%. iHS is better are mid-range values. Using a combination of these two techniques they found that six genes which are implicated in diseases characteristic of Ashkenazi Jews have the hallmarks of natural selection. Natural selection is self-evident, so what seems to have been going here is that the disease was simply a side effect or byproduct of adaptation.

The strongest signal they found was in ALDH2. The strongest signal in Europeans, LCT, was not found in Ashkenazi Jews. But is LCT a strong signal in Europeans? Many Southern European populations have low frequencies of the derived LCT allele, indicating that they haven’t been subject to strong selection for lactase persistence. These are the same populations genetically close to the Ashkenazi Jews. The authors suggest that the Jewish-European admixture occurred before the sweep of the derived LCT allele, but it seems more plausible that the Ashkenazim simply admixed with a European population, such as Italians, which do not exhibit much lactase persistence. As for ALDH2, the association between genetic variation on this locus and alcoholism is well known, and has been used to explain the low Jewish rates of the disease. In this case, the authors posit that protection from alcoholism is a positive side effect of natural selection:

The mechanism driving selection of the ALDH2 locus is unknown, but a plausible target of selection also within this selected region is the TRAFD1/FLN29 gene, which is a negative regulator of the innate immune system, important for controlling the response to bacterial and viral infection (49). TRAFD1/FLN29 may have conferred a selective advantage in the immune response to a pathogen, perhaps near the time that the Jews returned to Israel from their Babylonian captivity. Despite the unclear selective mechanism, this remains a remarkable example of a putatively selected region accounting for a known population phenotype.

Many of the other loci naturally did not show signatures of natural selection. But this sort of work is exploratory, and there are limits to the power of their techniques. As it is, it seems that we’re very far along on understanding the phylogenetic tree of the Jewish people, and we’re finally getting a grip on the exogenous parameters which might prune the branches.

Citation: Steven M. Bray, Jennifer G. Mulle, Anne F. Dodd, Ann E. Pulver, Stephen Wooding, & Stephen T. Warren (2010). Signatures of founder effects, admixture, and selection in the Ashkenazi Jewish population PNAS : 10.1073/pnas.1004381107

Related: John Hawks, New data on Ashkenazi population history.

Image Credit: Wikimedia

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A reader asked about the bizarre story of Adolf Hitler having “non-Aryan” ancestry. Specifically, The Daily Mail title is: “DNA tests reveal ‘Hitler was descended from the Jews and Africans he hated.’” Since it’s a British newspaper I frankly wouldn’t put it past them to simply pass along a hoax…but I think if they were going to do that they would have said it was the Cohen Modal Haplotype. The article claims that Hitler’s Y lineage was haplogroup E1b1b (all biological descendants of the same common male ancestor through the direct patriline will carry this set of Y chromosomal markers). This is really vague, as the haplogroup has many subclades. Obviously if you pull the lens far back enough you’ll find a phylogeny where Hitler and Jews and/or Africans are within the same clade. Dienekes notes that this is not a rare haplogroup. It is correct that if one is an Ashkenazi Jew the odds of one carrying this haplogroup are much higher. But, it is not necessarily entailed from this that one is likely to be an Ashkenazi Jew if one carries this haplogroup (or is of Ashkenazi Jewish descent).

This is clear from the map of the distribution of E1b1b’s two major subclades:

Even within Europe most men who carry this set of markers are not Ashkenazi Jews.

Of course this does not mean that Hitler wasn’t an Ashkenazi Jew. But there’s probably an easier way to find out if he had such ancestry: sequence his relative’s autosomal DNA. Ashkenazi Jews are genetically distinctive. The most common thesis I’ve heard is that Alois Hitler’s biological father was Jewish, which would make Hitler 1/4 Jewish, and his surviving great-nephew, Alexander, 1/16 Jewish. That’s probably enough to get a sense of whether this urban legend has any validity.

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On the heels of my post on cousin marriage, I thought readers might find this article on genetic screening in the United Arab Emirates of interest. One way to tackle the problem of genetic diseases which emerge out of consanguineous unions apparently isn’t to discourage the unions themselves, but dodge the outcomes. So pre-implantation screening of eggs as well as selective abortion of fetuses both seem to be options being evaluated. Aside from the costs, especially in the former case (though abortions are not without risk, and the initial stages of pregnancy are an investment of time as well), I still think there are long term problems with this. But first, Alan Bittles (who produced the map in the previous post) points to a major shortfall of a simple do-not-marry-cousins heuristic in this case:

People from the same tribe can also be highly genetically similar, he said.

“You can’t just compare the health of those children born of cousins but the comparison must be made within the tribes as well as between them, as some disorders are unique to particular tribes,” he said. “To stop consanguinity affecting health, you’d not only need to stop first cousin marriage but people in the same clan too, which is highly improbable and going against centuries of tradition.”

Another medical specialist opines:

Dr Anand Saggar, a clinical geneticist based in London, sees patients from the Gulf — who have been sponsored by their governments — at his clinic in Harley Street.

Western prejudice and health economics have led to the negative attitude towards cousin marriages, which are legal and accepted in many parts of the world, he said, pointing to Amish communities in the US.

“We’ll never get rid of any old genetic diseases because our genetic code keeps on mutating. You just have to accept that genetic disease is part of our evolution. It is a foolish and erroneous assumption that to stop marrying cousins would eradicate genetic disease.”

The National is paper based out of the United Arab Emirates, a former British colony. Therefore, I won’t put it past them to quote mine or distort (rule: beware of British newspapers!)…but this is just kind of a dumb assertion. The problem with inbreeding isn’t that one has deleterious alleles, it’s that there are correlations of deleterious alleles at the same locus. So the Jewish community has sharply reduced the manifestation of Tay-Sachs disease through genetic screening. The Amish community is is also impacted by recessive genetic diseases. As I noted earlier, inbred communities should have lower aggregate genetic load, and yet the the fact that deleterious alleles are concentrated on specific loci mean that they have reduced physiological fitness.

I’m skeptical of Alan Bittles assumption that there’s something set in stone about current Arab practices. Apparently miniskirts and exposed hair were de rigueur among the Arab female smart set in the 1960s, but now veiling is all the rage. Times change. But, the logical conclusion of generations of genetic screening of particular Arab lineages is that the clans of the Persian Gulf will eventually transform themselves into clones with very low mutational load. Even if the power of screening shields these lineages from the ill effects of inbreeding (by literally yanking out all the deleterious alleles from the gene pool by discarding eggs with problematic genotypes every generation), biological uniformity is going to have problematic long term consequences when it comes to battling co-evolving pathogens. Monocultures aren’t built to last.

In any case, interesting idea for a science fiction short story. The formula would be to take a pre-modern custom (e.g., cousin marriage) and mix it with future technology, and iterate forward.

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There is a new paper in Nature which is a full frontal attack on the utility of William D. Hamilton’s inclusive fitness framework in explaining eusociality. Martin A. Nowak, Corina E. Tarnita, & Edward O. Wilson are the authors. Wilson is famous in large part for his authorship of Sociobiology: The New Synthesis, and is arguably the doyen of American organismic biology. He is both an active scientist, and, a premier public intellectual. So with that in mind, I notice that Dienekes Pontikos alludes to “E.O. Wilson’s change of mind about group selection.” This is conventional wisdom, but it is I think wrong (though from what I can tell Wilson has not done much to disabuse the press of the notion). In Defenders of the Truth Ullica Segerstrale notes that Wilson did not expunge group selection thinking even in Sociobiology. In Evolution for Everyone David Sloan Wilson recounts that it was in fact E. O. Wilson who pointed out a group selective interpretation of data he was presenting at a conference, helping to push him early on in a rather unfashionable direction. From what I have heard Wilson always believed that the empirical data was not adequately explained by a pure inclusive fitness model, and simply waited until things shook out before pushing back with more theoretically trained colleagues who had the same skepticism.

From page 30 of Sociobiology:

…….Nevertheless, Williams’ distaste for group-selection hypotheses wrongly lead him to urge the loading of the dice in favor of individual selection. As we shall see in chapter 5, group selection and higher levels of organization, however intuitively improbable they may seem, are at least theoretically possible under a wide range of conditions. The goal of the investigation should not be to advocate the simplest explanation, but rather to enumerate all of the possible explanations, improbable as well as likely, and then to devise tests to eliminate some of them.

And page 129, the last paragraph in the chapter on group selection (quoted in full so there’ll be no confusions as to whether I’m pulling it out of context):

In conclusion, although the theory of group selection is still rudimentary, it has already providd insights into some of the least understood and most disturbing qualities of social behavior. Like Arjuna faltering on the Field of Righteousness, the individual is forcd to make imperfect choices based on irreconcilable loyalties-between the “rights” and “duties” of self and those of family, tribe, and other units of selection, each of which evolves its own code of honor. No wonder the human spirit is in constant turmoil. Arjuna agonized, “Restless is the mind, O Krishna, turbulent, forceful, and stubbon. I think it is no more aesily to be controlled than is the wind.” And Krishna replied, “For one who is uncontrolled, I agree the Rule is hard to attain, but by the obedient spirits who will strive for it, it may be won by following the proper way.” In the opening chapter of this book, I suggested that the science of sociobiology, if coupled with neurophysiology, might transform the insights of ancient religions into a precise account of the evolutionary origin of ethics and hence explain the reasons why we make certain moral choices instead of others at particlar times. Whether such understanding will then produce the Rule remains to be seen. For the moment, perhaps it is enough to establish that a single strong thread does indeed run from the conduct of terminte colonies and turkey brotherhoods to the social behavior of man.

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The map above shows the distribution of consanguineous marriages. As you can see there’s a fair amount of cross-cultural variation. In the United States there’s a stereotype of cousin marriage being the practice of backward hillbillies or royalty. For typical middle class folk it’s relatively taboo, with different legal regimes by state. The history of cousin marriage in the West has been one of ups & downs. Marriage between close relatives was not unknown in antiquity. The pagan emperor Claudius married his niece Agrippina the Younger, while the Christian emperor Heraclius married his niece Martina. Marriage between cousins were presumably more common. With the rise in the West of the Roman Catholic Church marriages between cousins were officially more constrained. Adam Bellow argues in In Praise of Nepotism: A Natural History that there’s a material explanation for this: the Roman church used its power over the sacrament of marriage to control the aristocracy. Though the church required dispensations for marriages between cousins of even distant degrees of separation, they were routinely given, as was obviously the case among Roman Catholic royal families like the Hapsburgs. But once given the dispensation could be revoked, rendering the marriage null and void. A highly convenient power politically.

But for much of European history the marriages of common folk were not of much concern to the church. Using ecclesiastical records L. L. Cavalli-Sforza documents very high levels of cousin marriage in Italy in the 19th century in Consanguinity, Inbreeding, and Genetic Drift in Italy. The rates dropped rapidly with economic development, especially better transportation networks in mountainous regions. I think this explains the patterns in the United States, extremely isolated communities are more inbred, while most Americans have traditionally been very mobile and not relied excessively on family networks. In northern Europe cousin marriage was not unknown in the 19th century, Charles Darwin famously married his cousin. With the Reformation official church sanctions against cousin marriage on the aristocracy and gentry were relaxed, and a few clusters of closely networked intermarried clans arose, such as the Darwin-Wedgewood family (the Catholic Church had also been a bulwark against forced marriages of aristocratic women, who always had life in a religious order as a possibility. The Reformation in Germany seems to have initially resulted in a sharp increase in the power of the patriarch over the marital fates of his daughters because of the removal of the religious safety valve as leverage). I think that the case of Charles Darwin and his social set speak to the attraction of cousin marriage: familiarity breeds affinity. In Victorian England a small group of closely related and affiliated elite gentry families, the Darwins, Keynes, Wedgewoods, Galtons, etc., created a subculture which spawned subsets such as the Bloomsbury Group.

With a more fluid and harshly meritocratic global elite the attraction of cousin marriage seems to have diminished in the Western world. Consider the tycoon Rupert Murdoch. He is an American citizen born in Australia married to a Cantonese woman with grandchildren who are 1/4 Ghanaian, 1/4 Dutch, 1/4 ethnic Scotch (Australian) & 1/4 ethnic Estonian (Australian) . As for the common people, geographical and social isolation is sharply mitigated by modern transportation networks, as well as larger scale non-kin institutions such as the Christian church. The same dynamics do not necessarily apply outside of the developed world. A friend whose father is Arab once explained that cousin marriage was so pervasive in that culture in part because you marry who you meet, and it is difficult in Arab societies for men to meet women who were not their cousins. In less individualistic societies where zero sum power dynamics are still operative it may also be beneficial for a wife to be related to the family into which she is marrying. Anthropologists in South Asia attribute the more equitable power dynamics between the genders in Hindu South India as opposed to more patriarchal Hindu North India to the fact that in the South cousin (and uncle-niece) marriage is practiced, while in the north exogamy is the norm. In the latter case a young woman leaves her family and becomes a “stranger” in her husband’s home. In the former case one of the new in-laws is a blood aunt or uncle.

But that’s the cultural anthropology. What may be fit for a cultural kin-unit may not be biological fit for individual lineages. What are the risks of cousin marriage? Most obviously there are recessive diseases. Those illnesses which are expressed when you carry two malfunctional copies of a gene. Cystic fibrosis, tay sachs, various forms of deafness. Why is it that cousins have a higher risk of this occurring? Because two cousins are much more likely than two random individuals to share the same distinct gene from a common ancestor, because their common ancestors are so much more recent. More precisely the coefficient of kinship between two first cousins is 1/8. That means that at any given locus there’s a 1 out of 8 chance that the two individuals will have alleles which are identical by descent, which means that the genetic variant comes down from the same person in the family line.

If the allele is “good,” that is, totally normal/wild type, not associated with any pathology, then we’re in the clear. That’s why most first cousin marriages don’t produce children who are monsters. What a first cousin marriage does is change the odds. How you present these odds matters a great deal in how scary they sound. If I told you than the chance of first cousins having children with a birth defect is 4-7%, vs. 3-4% for a non-consanguineous couple, it might not sound that bad. But if I told you that the odds of having a birth defect is ~50% greater, then it sounds worse. Additionally, the costs of congenital illness are born by the offspring, and society through health insurance premiums. If you compared a society which had a tradition of universal first cousin marriages vs. one which didn’t, you’d see 50% more birth defects in the former society in the aggregate, all things equal.

But that’s the not the only issue there. There are two opposing forces which diminish the problems of common cousin marriage and make it worst. The first is the purging of genetic load which occurs when you expose deleterious recessive alleles. Remember that low frequency recessively expressed alleles aren’t exposed to natural selection because they’re mostly found in heterozygotes. This means they get to float around in the gene pool for very long periods of time. In plant breeding you can just “self” the plants, which will expose the alleles rather quickly, since selfing is an extreme form of inbreeding, purging heterozygosity. The deleterious alleles then are removed from the gene pool through the death of individuals who carry them in homozygote state. The theory is that some human populations which practice cousin marriage at higher frequencies may have a lower frequency of deleterious recessive alleles. Alan Templeton reports this for South Indian Hindus in Population Genetics and Microevolutionary Theory, and L. L. Cavalli-Sforza does the same for the Japanese in the aforementioned monograph. In the proximate sense this purging of the genetic load occurs through human misery. The early death of individuals, or their sterility, or sharply reduced fertility because of illness. In the ultimate sense it’s somewhat speculative, and many geneticists are skeptical that complex mammals are easy to analogize with plants which do occasionally self in the wild.

That’s the positive genetically. What’s the negative? Pedigree collapse. I’ve been talking about marriages between first cousins throughout this post, but that’s really a small issue next to this. Even first cousin marriages produce individuals with a fair amount of inbreeding. I ran a test for runs of homozygosity in my 23andMe genetic profile and I got 3 hits, while a friend whose parents are first cousins got ~70 (the parameters for the test aren’t important, just giving a relative sense). For inbred clans it gets much worse because people are related in many different ways, and genetically are far closer than first cousins. That is what happened to the Spanish Hapsburgs. As you can see from the pedigree of Charles II his parents were closer than typical first cousins. The Samaritans of Israel are a religious sect which seems to be going through pedigree collapse. Some of them are proactively marrying outsiders to prevent their extinction through high infant mortality rates. Others, “traditionalists,” oppose exogamy because intermarriage within the group is the custom, and diseases are God’s will.

The Samaritans are an extreme case. But we may be seeing a thousand Samaritan flowers blooming across the Middle East. From what I know cousin marriage in the Middle East is not limited to Muslims, Christians and Jews practice it as well. But among many Muslims it has some cachet because of particular hadiths which point to this practice as preferred. Setting religion aside, there are also social reasons why this practice is common. As I noted above sex segregation means that you may not know women outside of your family well, and in some societies where veiling is practiced it may be that you do not see many women you are not related to (even if veiling occurs at puberty, you may have seen your cousin at a younger age). Marriages are bonds which may tie a family into one operational social unit, and so produce a powerful inbred clan. This illustrates the cross-purposes of a cultural unit of selection vs. the individual unit of selection. In a society where clan vs. clan competitions are critical sorting mechanisms consanguineous marriages may serve as beneficial cross-linkages. Balanced against this of course are marriages across clans. On an individual level a first cousin marriage reduces the reproductive fitness, but higher potential reproductive fitness of two individuals who have no social support because of ostracism may be a moot point.

From my cursory reading of the literature consanguineous marriage is not declining in much of the Muslim, especially Arab, world. Why? I can think of two superficial reasons obvious to someone like me, who is no anthropologist or sociologist with area knowledge. First, high fertility rates and lower infant mortality means that the sample space of possible matches increases. One way you can remove the option of cousin marriage is by shrinking the pool of potential cousins you may marry. In a Malthusian world the average family has only two children who manage to survive to adulthood and reproduce. The variance around this expectation means that many families will disappear within two or three generations simply due to stochastic forces. This is why Augustus attempted to use moral suasion and coercion to have the Roman Senatorial class reproduce at a higher rate. The aristocracy was going extinct as clans which were defined by a legitimate male line succession would routinely have a generation without a male heir (this explains the popularity of adoption in Roman society, with adoptees often being younger sons of related lineages). Later in imperial history Marcus Aurelius and his maternal cousin, Faustina the Younger, had thirteen children, but only four survived to adulthood. The modern world is very different, and great clans can rise in just a few generations if one has the will. A second reason I believe that cousin marriage is popular in the Arab world is economics. Specifically, commodity/resource driven economic growth doesn’t require great median human capital investment, so there isn’t an incentive to shift toward a less familial social structure. In plain English going to university, moving regularly for your career, etc., are going to weaken the bonds of affinity you may have with your family. This is not necessary for many Gulf Arabs, who have a guaranteed a minimum income because of resource revenue. Not only has this allowed them to preserve a relatively archaic set of social norms, but I believe it’s also allowed for the baroque elaboration of their customary traditions. I don’t find the second explanation persuasive for most Muslim nations though, as they aren’t as reliant on resource driven revenue, and have had to make more accommodations with the exigencies of the modern world. I believe that in all likelihood large families are probably responsible for the resurgence or persistence of the practice in societies where it has been the preferred pairing.

This post was inspired by a recent Channel 4 special, When Cousins Marry: Reporter Feature. If you live in Britain you can probably watch it online (I can not). But it highlights that the issue is going to be salient in the United Kingdom for a generation or so at a minimum. As I said, in the United States inbreeding is a way to make fun of poor, uneducated, and isolated whites. The photo to the right is from a blog entry mocking anti-Obama activists who were protesting his address to the children of the nation as “racist, inbred hicks.” The American perception of inbred people is not particularly positive, and the accusations of being inbred are used to mock and humiliate. But when it comes to the issue in Britain it is different, because consanguineous marriage is a feature of the Muslim community, and there are issues of race, religion and class which are operative. It isn’t just custom and tradition which are driving people to marry their cousins in Britain (perhaps more accurately, parents are demanding their children marry their cousins). Marrying one’s cousin is a rather convenient way in which to allow more of your relatives to immigrate. In a subculture where arranged marriage is the norm the marrying a cousin abroad seems eminently rational for the clan’s prospects. But there are other forces at work in the community which perpetuate and encourage it as well, and those forces can not be frankly addressed because of the tensions which are normal in many multicultural societies. From the summary of the program:

‘An attack on Pakistani culture’

However I also spoke to some people in cousin marriages who felt there were great benefits and questioned if it was yet another aspect of their culture that was coming under attack.

This sentiment has been echoed several times during the making of this Dispatches programme. It’s a subject that has provoked a defensive and sometimes hostile reaction every time we’ve touched upon it. We spoke to dozens of families who refused to talk about it on camera and we were told frequently that even to discuss the issue was an attack on Pakistani culture or worse still, Islam.

Since Britain has the NHS this is a going to be a major public health issue. On the one hand, there is individual freedom of choice. This is a core Western value. On the other hand, there is the fact that health care costs are a long term structural issue for the fiscal health of any society. Ethnic Pakistanis are only a few percent of Britain’s population, so it is manageable right now, but their proportion will slowly rise because of higher fertility and continued immigration. If cousin marriage continues to remain popular in the community the later generations are going to have even greater health problems because of higher inbreeding coefficients (due to repeated cousin marriages across the generations within the family).

But why should we limited these sorts of social utilitarian considerations to cousin marriage? How about the increased debilities associated with the children of older mothers? Mothers who make recourse to assisted reproductive technology such as in vitro fertilization? Lines have to be drawn. Costs and benefits have to be evaluated. With the passage of health care reform in the United States in 2010 the issue is now explicitly socialized in all developed nations. I began the post with a social-cultural narrative, and I end it with a reiteration of the importance of a social-cultural context.

Image Credits: Wikimedia, Consang.net, youoffendmeyouoffendmyfamily

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Mike the Mad Biologist, whose bailiwick is the domain of the small, asks in the comments:

I don’t mean to bring up a tangential point to the post, but why does the field of human genetics use PCA to visualize relationships? When I see plots like those shown here that have a ‘geometric pattern’ to them (the sharp right angles; another common pattern is a Y-shape), that tells me that there are lots of samples with zeros for many of the Y-variables (i.e., alleles that are unique to certain populations). Thus, the spatial arrangement of the points is largely an artifact of an inappropriate method: how does one calculate a correlation matrix when many of things one is correlating have values of zero?

If one really was keen on using PCA, one could calculate a pairwise distance matrix and then use that instead of the correlation matrix (Principal Coordinates Analysis).

Since I know some human geneticists do read this weblog, I thought it was worth throwing the question out there.

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Last week I took an intellectual road trip back nearly a century and explored the historical context and scientific logic by which R. A. Fisher definitively fused Mendelian genetics with quantitative evolutionary biology. In the process he helped birth the field of population genetics. While the genetics which we today are more familiar with begins at the biophysical substrate, the DNA molecule, and the phenomena which emerge from its concrete structure, population genetics starts with the abstract concept of the gene. This abstraction and its variants are construed as algebraic quantities from which one can infer a host of dynamics. These are the processes which are the foundations of evolutionary change, as population genetics flows into evolutionary genetics, and ultimately the raw material of natural history.

Fisher’s accomplishments were a function of both his abilities and his passions. He was a mathematical prodigy, with the ability to distill natural processes down to highly general abstractions. And like many English gentlemen of his age he had a passion for evolutionary biology, and cherished his copy of The Origin Of Species. His ultimate aim was to transform evolutionary biology into a discipline with the same analytical rigor as physical chemistry. But he wasn’t the only major figure on the scene in his era.

Sewall Wright was an American physiological geneticist with a background in animal breeding. While Fisher was a mathematician who sought to apply his skills to evolutionary biology, Wright was a biologist who taught himself mathematics to further his own understanding of evolutionary processes. The two were in many ways the Yin and the Yang of early population genetics, with their conflicts and disagreements being termed the Wright-Fisher controversies, and the common formal framework which they converged upon becoming the ubiquitous Wright-Fisher model. Wright’s life spanned 99 years, from 1889 to 1988. His biography, both personal and scientific, are explored in rich detail in Will Provine’s Sewall Wright and Evolutionary Biology. Because of the length and breadth of his influence in evolution it’s worth reading just to get a sense of how Wright shaped the Modern Neo-Darwinian Synthesis behind the scenes. Provine seems to indicate that Wright was the primary theoretical influence on Theodosius Dobzhansky,* who mentored a whole generation of evolutionary biologists to come (e.g., Dobzhansky → Lewontin → Coyne).

If I may make recourse to analogy, if R. A. Fisher was the Alfred Marshall of evolution, Sewall Wright’s mentality seems more characteristic of Thorstein Veblen’s work. Fisher’s aim was to formulate elegant and simple general principles which would explain evolutionary process top to bottom. His fundamental theorem of natural selection, “The rate of increase in fitness of any organism at any time is equal to its genetic variance in fitness at that time,” was perhaps the best example of Fisher’s grand general ambitions. Wright, by origin an experimental biologist, certainly aimed for grandeur, but I can not perceive in him the yearning for a clean concise elegance which discards the sloppiness he saw in evolution as it played out in the laboratory. This inability to ignore the detail was a “bug” which he in some ways turned into a feature when it came to his theorization of evolutionary process.

Many of the ideas which would be the focus of Wright’s career, and later shape the outlook of his acolytes, can be found in a 1932 paper The roles of mutation, inbreeding, crossbreeding and selection in evolution. In this paper Wright introduces concepts which are still with us today, and reviews the state of knowledge at the time. Some of his observations are almost amusing now 80 years later. He suggests that multicellular organisms likely have more than 1,000 genes. Wright also alludes to concepts such as allopatric speciation and postzygotic reproductive isolation which have spawned an enormous literature, and are the stuff of careers..

But the core of the paper seem to be the adaptive landscape and the shifting balance. What is the adaptive landscape? If you follow Will Provine’s reading no one really knows! OK, to be fair, the landscapes usually describe a topography where fitness is on the vertical y-axis, and x and z are frequencies of genes, or perhaps phenotypes. But are they frequencies within a whole population? Or do they represent genotypic combinations within individuals? Over the decades of the utilization of the metaphor Provine indicates that Wright and his students had different ideas of what the metaphor was in the specifics, suggesting its Rashomon-like aspects. The idea of landscapes across which evolution traverses over time is a very easy to visualize, but making use of the framework in a concrete sense is more difficult. This was especially so in the days before computer programs which could produce beautiful multi-dimensional visualizations.

To the right you see a primitive representation of a fitness landscape from Wright’s paper. The y & x axis are different genes, and at their intersection you have a gene-gene combination. There are several ideas at work in these evolutionary landscapes. The first of them are gene-gene interactions, epistasis. It is often asserted that Wright and Fisher disagreed on the importance of epistasis in evolution, with Wright arguing that these interactions were critical, and Fisher dismissing their long term importance. There are other interpretations, and much of the disagreement may actually have been more about fine weights than the basic thrust of their positions. But the general sketch is that biologists in the Fisherian tradition emphasize gradual continuous evolution through selection on additive genetic variance across genes of small effect through natural selection (I understand that this is somewhat a caricature of Fisher’s own views, and most of his intellectual descendants view this description as the creation of their critics, but that’s the perception). The Wrightian tradition is more pluralistic, and frankly somewhat confused because different thinkers have different spins (e.g., epistasis vs. drift). But in general it suggests that factors such as population substructure, gene-gene interaction, and random genetic drift, all play crucial roles in evolution. The partisans of contingency in evolutionary process and the importance of specific genetic architecture in constraining and shaping the arc of change would likely get more sympathy from Wright.

For Sewall Wright the specific nature of the fitness topography is critical in shaping how evolution plays out on the genetic level. If the topography is “rugged” so that there are many fitness peaks and valleys of disparate values along the y-axis, then populations may become “trapped” on a lower peak which is separated from the higher one by a valley. The movement of a population along the adaptive landscape clearly has a temporal interpretation, and so one can see how contingency and history are critical. Where you start out from may constrain where you can end up. At least, if you rely on conventional deterministic processes such as natural selection on a single locus. This is where Wright suggests that populations structured so that their effective sizes are smaller can evolve much faster, and leap across the valley’s so to speak, through the action of random genetic drift. It may be that to attain a given gene-gene combination (or gene-gene-gene-gene, etc.) is nearly an impossible proposition in a deterministic framework where one has to proceed on a step-by-step basis, but through the luck of random genetic drift one can envisage the odds being reduced by a few chance deviations in allele frequency.

Because Wright posits that much of evolution occurs by scaling a sequence of distinct and disparate adaptive peaks, he implicitly rejects gradualism and embraces discontinuity and rapid bursts of evolution. This sort of process occurs in a situation with moderate population substructure, so that effective population size is reduced within demes which then can “peak shift” more frequently, but, with enough population-to-population interaction that inbreeding does not drive mutational meltdown or pedigree collapse.  When a subpopulation reaches a particularly fortuitous adaptive peak, then it enters a phase of demographic expansion, and it can replace all the other demes of conspecifics (or at least genetically assimilate them to a great degree). This is where Sewall Wright introduces intergroup selection, or more colloquially group selection. Here Wright and Fisher part company again, naturally. Fisher believed that individual level selection was sufficient to explain evolutionary process, while Wright clearly did not. The debate between those who believe that group selection is a significant force in evolution, and those who do not, continues to this day (group selectionists now have a more general model, multilevel selection theory).

Epistasis. Drift. Moderate population structure and migration. Add to the mix mutation and selection, as well as the fact that the adaptive topography itself is in constant flux, and Wright already has the beginnings of a strong brew in The roles of mutation, inbreeding, crossbreeding and selection in evolution. I’ve only glanced over a few of the points. In other sections Wright touches upon what would one day become mutational meltdown, as well as the nature of speciation. There are many disparate threads here which would eventually lead into a range of disparate research programs.

So with that I want to get to my “human obsession.” Near the end of the paper Sewall Wright seems to offer that the emergence of our own species could be well characterized by a shifting balance model. I suspect that Wright may be right on this. The movement out of Africa was a great pulse, where one human lineage seems to have rapidly replaced or genetically assimilated all the others. Human populations do have substructure, but they also exchange genes, and leapfrog each other. Our cultures may be the perfect vehicles for intergroup selection on the memetic, if not genetic, level (between group variance in memes can be much greater than on genes). I suspect this is not going to be age where elegant one-size-fits-all theories are going to be of particular use, so we might want to dig back into Wright’s diverse set of ideas.

* More directly though he came out of the Morgan lab.

Citation: Sewall Wright (1932). The roles of mutation, inbreeding, crossbreeding and selection in evolution Proceedings of The Sixth International Congress of Genetics, 1

Related:

Notes on Sewall Wright: The Shifting Balance Theory – Part 1

Notes on Sewall Wright: The Shifting Balance Theory (Part 2)

R. A. Fisher and the Adaptive Landscape

R. A. Fisher and Epistasis

Notes on Sewall Wright: the Adaptive Landscape

Notes on Sewall Wright: Migration

Notes on Sewall Wright: Population Size

Notes on Sewall Wright: Wright’s F-statistics

Notes on Sewall Wright: Genetic Drift

Notes on Sewall Wright: the Measurement of Kinship

Notes on Sewall Wright: Path Analysis

Wright, Fisher, Haldane, and odds and ends

Image Credits: Evolutionary Systems Biology, Wikimedia, Scholarpedia, Science

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Last year a paper came out in Science which made a rather large splash, The Genetic Structure and History of Africans and African Americans by Tishkoff et al. Since it’s more than a year old I recommend that those of you curious about the details of the paper and don’t have academic access go through the free registration, as you can then read it in full. Unlike Reich et al. the Science paper didn’t unveil a new method of analysis. It was the standard bread & butter, with PCA’s & STRUCTURE plots & phylogenetic trees. But the coverage of populations within Africa was massive. They had a lot of results and relationships to cover, and ended up with a 100 page supplement.

I commend the whole paper to you. But there are two elements I want to highlight. First, a three dimensional PCA plot. It has the first, second and third principal components of variation. In other words, the three largest independent dimensions in terms of explanatory power of genetic variation. Panel A includes all world populations, and panel B just Africans.

For panel A, PC1 = 20% of the variance, PC2 = 5%, and PC3 = 3.5%. For panel B the PCs didn’t drop off quite so much, PC1 = 11%, PC2 = 6%, PC3 = 5% and PC4 = 4%. In case you don’t know, the Hazda are Africa’s last obligate hunter-gatherers, and speak a language with clicks in it, just as the Bushmen do. The big division highlighted in this paper is that between the “indigenous” relict populations, the Hazda, Sandawe, Bushmen and Pygmies, and those who belong to the more widespread agriculturalist and pastoralist societies of Africa. Implicit within the paper is the model of a Bantu Expansion of farmers, as well as a possible later Nilotic expansion (which brought the Tutsi and Masaai) of herders, in a north-south direction. In the process they assimilated/and or/displaced the indigenous populations, of whom the aforementioned peoples are relict islands persisting in ecologically isolated or unfavorable domains.

The map to the left shows the population coverage within this paper of African groups. The pie graphs simply show ancestral quanta as inferred by STRUCTURE. You can read the paper for the blow-by-blow. But ultimately it seems there will be need for a finer-grained coverage to the south of the equator. If the Bantu expansion is as recent as archaeologists and linguists assume, on the order of ~2,000 years ago, then the gradients of genetic signals should persist. From what I can tell it is assumed on both genetic and phenotypic grounds that the Xhosa have a higher load of Khoisan ancestry than the Zulu or Tswana. The Bantu Expansion is recent enough that the semi-legendary Phoenician circumnavigation of Africa would have encountered many Khoisan peoples along the eastern coast.

Below are a selection of figures from the above paper. After selecting an image it is probably best to hit F11 for “Full Screen” if you aren’t a on a very big monitor (you can copy image location and view it in a separate window as well).

[View with PicLens]

Genetic Variation by Distance

Unrooted Tree Africa

Unrooted Tree

Genetic Distance Tree 1

Genetic Distance Tree 2

Genetic Distance Tree 3

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