history

Bray and colleagues [1] report on genotyping of 471 people of Ashkenazi Jewish descent. This is one of the largest samples of a single human population, and is therefore very interesting for studies of population history and recent natural selection.

There's a lot in the paper. One of the key findings in the paper is that the Ashkenazi population doesn't look bottlenecked -- in fact, it looks outbred compared to Europeans generally. The paper also documents a high amount of admixture with non-Ashkenazi Europeans, ranging from 35% to 55%. Figuring out the actual history of the population -- when and where its ancestors lived and how they interacted with other people -- is beyond the scope of this kind of analysis. But I expect that somebody can put together a really compelling historical account using these data.

I turned quickly to the issue of selection. They are able to substantiate evidence of positive selection on several disease-causing alleles in the Ashkenazi population, including the Tay-Sachs allele. The lack of evidence for bottlenecks or founder effects pretty much takes away the alternative explanation. Yet they were unable to show statistical evidence of selection on some other disease-causing alleles in Ashkenazi populations:

To explore whether regions of selection in the AJ population included any loci of known Ashkenazi diseases, we examined 21 disease- and cancer-susceptibility loci with known mutations found at higher frequency in the Ashkenazi population. Only 6 of the 21 genes fell in or near (within 500 kb) the top 5% of the AJ iHS windows (Table 2). Among these is the Tay-Sachs disease gene, HEXA, whose selection has been widely debated (4, 5, 14–16) and was found ~400 kb downstream of a window on chromosome 15 identified in the top 1% of the AJ iHS hits. Although none of the SNPs interrogated immediately adjacent to the HEXA locus showed elevated iHS signals, it is possible that the nearby region may contain regulatory elements under selection that affect HEXA expression. Cochran et al. (14) speculated that selection of many of the AJ- prevalent disease loci, especially the lysosomal diseases, conferred an increase in intelligence that was necessary historically for the AJ economic survival. Our data shows evidence of strong selection at or near only six disease loci, including only one out of the four AJ- prevalent lysosomal storage diseases, thus arguing that most AJ disease loci are not under strong positive selection, but rather rose to their current frequency through genetic drift after a bottleneck. However, we cannot exclude the possibility that selection of some AJ disease loci are outside the limits of detection by the extended haplotype tests, which are known to have less power to detect se- lection of lower frequency alleles (38, 41).

It seems to me that this passage probably wasn't written by the same author who showed the lack of evidence for founder effects a few pages before. In this case, the confusion probably comes from the fact that the "detection of positive selection" is actually a refutation of the hypothesis of genetic drift. With a larger sample it will be possible to test the hypothesis with greater power.

Ddisease-causing alleles are at low frequencies currently, making them unlikely to rise to the top percentages of the statistics. It would be interesting to control for current frequency, but I haven't seen a test that uses frequency information in this way.

It's quite remarkable to reflect on the idea that positive selection has now been demonstrated on six disease-causing alleles in the Ashkenazi population. Every one of these is a case of overdominance -- where the heterozygote carrying an allele has some selective advantage, while the homozygote carrying two copies has a disorder. I was having a conversation with a very prominent geneticist a few months ago, who claimed that no case of overdominance in humans had ever been demonstrated except sickle cell. Now, that was obviously false even at the time -- as I pointed out, the many hemoglobinopathies are fairly clear examples. But we've come an awfully long way.

From data like these, we're going to learn a huge amount about low-frequency selected alleles. The Tay-Sachs-causing allele is one of the most common recessive lethal genes in any human population, but like all genes subject to strong selection in homozygotes, it remains rare. Finding selection on these kinds of alleles is very hard unless sample sizes increase to several hundred individuals. Here we are seeing evidence of selection in historic populations -- within the last 2000 years. More will be coming.

References

An interesting study has shown how people in the samurai class of Edo period Japan were poisoning their children with lead. The results are reported in a current paper in the Journal of Archaeological Science by Tamiji Nakashima and colleagues [1]. They applied forensic techniques to skeletal remains from the period.

Lead poisoning has long been suspected as a factor affecting the aristocracy of late imperial Rome. There, the causes were mainly in the plumbing, made as it was from plumbum. But in Japan, the guilty party was makeup:

In view of the higher contamination in female bone than male, we assumed that facial cosmetics (white lead) were one of the main sources of lead exposure. During the Edo period, cosmetics became popular and the vogue was usually introduced by Kabuki actors, courtesans and geisha through ukiyoe prints and popular literature, and by beauticians who helped establish fashions. The white face powders used in those days were keifun (mercury chloride) and empaku (white lead). Mercury chloride was imported mainly from China, and white lead was popular in Japan, although the toxic nature of lead cosmetics was not recognized. Ikutarou Hirai, the first professor of the Department of Pediatrics at Kyoto University, revealed in 1923 that “so-called tentative meningitis” of infants was actually caused by lead-containing face powder used by mothers (Horiguchi, 2006).

They haven't been explicit about how the lead was transferred from mother to infant, it may just have been incidental contact and consumption. The consequences were in a few cases severe:

From the anatomical point of view, there were five cases in which anomalies of bone were seen (Fig. 1). These were hypertrophy of the long bones and a few lead lines or lead bands. These roentgenographic pictures of dense metaphyseal bands seen in the growing long bones of children with lead poisoning are familiar to radiologists (Leone, 1968). These anomalies were seen in all the long bones of the upper and lower extremities in the five cases. Sachs (1981) reported that the appearance of a lead line required a minimum blood lead concentration (PbB) of 70-80 μg / dL.

They also speculate as to possible psychopathology resulting from the lead exposure.

I think it's interesting to find these cases where technology, adopted first by the elites, ends up biting them with unanticipated side effects. Usually they don't even know what hit them.

References

I'm always skeptical when pathologists attempt to diagnose the ills of historical figures. Even if there are medical records or abundant attestations of symptoms from contemporary sources, people in the past had different ways of describing the observations that doctors today collect.

But that doesn't stop people from trying. Last month, John Hayman published a paper in the British Medical Journal that claims a new diagnosis for the lifelong malady that Darwin described in his own journals and correspondence:

Darwin’s symptoms are those of cyclical vomiting syndrome. Although this is primarily a disease of children it may persist into adulthood or may appear for the first time in adulthood. The disease is related to classic migraine and abdominal migraine but is also linked to abnormalities of mitochondrial DNA, with mutations in the MTTL1 gene. This disease is neither well known nor well recognised, particularly in adults, although it was first described in the English literature in 1882.

People with cyclical vomiting syndrome experience abdominal, circulatory, and cerebral symptoms, including headaches and anxiety. Symptoms overlap with those of classic and abdominal migraine, except for a lack of aura. Affected people may experience some or all of these symptoms, with each individual having similar symptoms with each episode. Over time, however, progression or change may occur in the most prominent feature, and episodes may coalesce. Many people report severe motion sickness, and this may be associated with a full episode.

It seems plausible enough, as much so as any retrospective diagnosis could probably be. It bears all the drawbacks of other attempts to diagnose historical figures.

A test of the hypothesis: mtDNA is maternally inherited and haploid, so symptoms are very likely to be shared by maternal relatives:

Darwin’s mother Susannah died with abdominal pain when he was 8. As a child she had vomiting and boils, experienced motion sickness, had excessive sickness during pregnancies, and "was never quite well." Her younger brother Tom had similar symptoms, with headaches, abdominal pains, and motion sickness. A sister, Sarah, considered that Charles and his uncle Tom had the same illness. Evidence of a matrilineal inheritance pattern is good, consistent with an abnormality of mitochondrial DNA.

It's a sad thing to affect a family.

Mitochondrial disorders are increasingly recognized as causes of chronic disease -- just the other day, a new study implicated defective mitochondria as causes of Parkinson's Disease. I think it's hilarious because there is a cadre of geneticists who depend on the notion that mtDNA is a neutral marker of population history.

Darwin's DNA has nothing to say about whether it was neutral on an evolutionary timescale, but every famous mtDNA functional mutation reminds us that there is biological function there, which is a target of selection under some circumstances.

(via Why Evolution Is True)

References:

Hayman JA. 2009. Darwin's illness revisited. Br Med J 339:b4968. doi:10.1136/bmj.b4968

I've intermittently been reading through William Provine's The Origins of Theoretical Population Genetics. It's related to a project simmering on my back burner.

Meanwhile, last week I was talking with some students about the recent papers at the AAPA meetings about natural selection as assessed by quantitative traits. The students thought that some of these papers had omitted some basic details that seemed obvious from the point of view of quantitative genetics. Also, George Armelagos had mentioned Raymond Pearl, so I figured as long as I'm reading about Pearl, William Castle, R. A. Fisher and their attitudes toward quantitative genetics, I might as well note a few passages from Provine's account.

Provine:

Fisher's express purpose in the paper was to interpret the well-established results of biometry in terms of Mendelian inheritance by ascertaining the biometrical properties of a Mendelian population.

I'll just pause to note that Fisher's formulation begins almost all textbooks in quantitative genetics and many in population genetics. The model that relates quantitative variation and genotypic variation is essential to all genetic analysis.

In particular, he wanted to show that Pearson was mistaken in concluding that the correlations between relatives in man contradicted the Mendelian scheme of inheritance. He began by defining a measure of the variability of a character in a population.

This is an essential step for any introduction to genetics also. I spend some time in all my courses talking about the relationship between genetic and phenotypic variation, using the measures of each as ways to talk about the ways they differ. We can analogize genetic variation to a digital readout -- you have a genotype, or a set of genotypes, and the population's variation has to do with the frequencies of those genotypes or the alleles that comprise them. So the variation is something that emerges from counting genes. You have heterozygosity (expected frequency of heterozygous genotypes), or number of alleles. At the sequence level, you count both alleles and the number of mutations that separate them -- average pairwise difference, number of segregating sites.

Back to Provine:

Often the standard deviation σ was used for this purpose. But Fisher noted that

Now Provine gives a direct quote from Fisher 1918:

when there are two independent sources of variability capable of producing in an otherwise uniform population distributions with standard deviations σ₁ and σ₂, it is found that the distribution, when both causes act together, has a standard deviation σ₁² + σ₂². It is therefore desirable in analysing the causes of variability to deal with the square of the standard deviation as the measure of variability. We shall term this quantity the Variance of the normal population to which it refers, and we may now ascribe to the constituent causes fractions or percentages of the total variance which they together produce (Fisher 1918:399).

I have always thought that this was a work of magic by Fisher. The additive quality of variance is such a useful characteristic for a measure of variation, it's hard to imagine using anything else. Fisher continues:

For stature the coefficient of correlation between brothers is about .54, which we may interpret by saying that 54 per cent of their variance is accounted for by ancestry alone, and that 46 per cent must have some other explanation.

It is not sufficient to ascribe this last residue to the effects of environment. Numerous investigations by Galton and Pearson have shown that all measurable environment has much less effect on such measurements as stature. Further, the facts collected by Galton respecting identical twins show that in this case, where the essential nature is the same, the variance is far less. The simplest hypothesis, and the one which we shall examine, is that such features as stature are determined by a large number of Mendelian factors, and that the large variance among children of the same parents is due to the segregation of those factors in respect to which the parents are heterozygous. Upon this hypothesis we will attempt to determine how much more of the variance, in different measurable features, beyond that which is indicated by the fraternal correlation, is due to innate and heritable factors (Fisher 1918:400).

And that, in a nutshell, is why the correlation between relatives is not a measure of heritability. Fisher attempted to show that the segregation of Mendelian factors could account for a large fraction of the variance of stature, and substantially succeeded in showing that the environment had much less impact than had been assumed from the correlation between relatives.

Provine's discussion continues along a different line, but he includes the characteristic line:

Fisher's 1918 paper was well received by the few geneticists who could understand his mathematics (147).

I think that this NY Times story by Noam Cohen, titled "In Douglass Tribute, Slave Folklore and Fact Collide," is just fascinating. It's an old story (from early 2007), but I was pointed to it this morning.

At the northwest corner of Central Park, construction is under way on Frederick Douglass Circle, a $15.5 million project honoring the escaped slave who became a world-renowned orator and abolitionist.

Beneath an eight-foot-tall sculpture of Douglass, the plans call for a huge quilt in granite, an array of squares, a symbol in each, supposedly part of a secret code sewn into family quilts and used along the Underground Railroad to aid slaves. Two plaques would explain this.

The only problem: According to many prominent historians, the secret code — the subject of a popular book that has been featured on no less a cultural touchstone than “The Oprah Winfrey Show” — never existed. And now the city is reconsidering the inclusion of the plaques, so as not to “publicize spurious history,” Kate D. Levin, the city’s commissioner of cultural affairs, said yesterday.

Read the story if you're interested. I really have no opinion, other than to point out that Oprah's programs have often promoted pseudoscience and myths. In this case, the story comes from a 1999 book, Hidden in Plain View. According to Cohen's article, the authors do not currently claim that the secret codes really existed at the time of the Underground Railroad or were widespread; they say that this was one family's story.

What I think is interesting is that the story has developed such a following among educators and otherwise knowledgeable people:

There are currently 207,000 copies in print, she said. The codes are frequently taught in elementary schools (teachers have been eager to take up the quilting-codes theory because of its useful pedagogic elements — a secret code, artwork and a story of triumph), and the patterns represent a small industry within quiltmaking.

I suppose many historians find this maddening -- sure, there's no documentary evidence, a believer would say, because the codes were secret! But then, that's the defense for most conspiracy theories, from UFOs to the Illuminati.

Oprah aired the story along with the Jefferson DNA descendants, in the news at the same time:

On Ms. Winfrey’s show, Dr. Dobard appeared with the black descendants of Thomas Jefferson. That relationship was preserved in oral history across the centuries, even as historians of the past generally dismissed the claim. DNA tests published in 1998 are considered to have confirmed Jefferson’s paternity.

So, Oprah helped make an anthropology link for me to hang the story on. A family story, doubted by the historical establishment, yet proved with DNA. Well, maybe at least -- in the DNA case, there are other paternal Jefferson relatives who might have been the ancestor.

No doubt a good historian could test this hypothesis too. I would look at the question as an opportunity to study a lot of interesting quilts and other folk art. Do a phylogenetic analysis on elements included in early quilts. Few of these will date to the pre-Emancipation period, but if the elements of the story -- a star, zig-zags, monkey-wrenches -- were sufficiently common and co-associated in later quilts, say, from the 1930's, it would be an argument in favor of the widespread existence of the pattern at an earlier time.

Ancient DNA technology may make it possible to test some very interesting hypotheses about recent evolutionary change in human populations.

Meanwhile, several people are reporting the potential of DNA from museum specimens for testing hypotheses about ancient or extinct populations. Today's news includes a story introducing the term "museomics" -- otherwise known as the metagenomics of museum specimens, including the DNA of taxidermed specimens and their pathogens and commensal bacterial populations:

[Webb] Miller and his team used state-of-the-art DNA sequencing technology to analyze the hair of two preserved specimens: a female thylacine that died at the London Zoo in 1893, and a male brought to the National Zoo in 1902 that died three years later.

Although the two thylacines were continents apart, their mitochondrial DNA — a portion of the genome passed on via the maternal line — was nearly identical, illustrating the species' ultra-low genetic diversity around the turn of the 20th century.

Brandom Keim of Wired blogs that medieval parchment preserves enough DNA for analysis:

Initial tests showed that the animal skin pages contained enough intact DNA to make analysis worthwhile. So [Tim] Stinson and his brother Mike Stinson, a biologist at Southside Virginia Community College, skin samples taken from five pages of a 15th century French prayer book. Preserved mitochondrial DNA revealed that the pages came from two closely related calves.

Those results, said Stinson, are a proof of principle that it's possible to create a DNA database from manuscripts of known age and origin. Monastic paperwork tended to be dated, so DNA from those works could be cross-indexed with that of literary works from tomes of unknown provenance, producing a taxonomy of manuscript manufacture.

Sourcing manuscripts is pretty exciting to historians, no doubt, who must otherwise rely on indicators such as handwriting style and dialect.

But the results may be equally useful for understanding the processes of animal breeding in medieval Europe. Today's domesticated breeds are a remnant of a much larger diversity of local breeds that once existed. People bred animals both locally by selection and across large regions by introducing favored animals from long distances. Sometimes they favored diversity -- and considering the revival of interest in legacy breeds like Highland cattle.

As an example, today's European swine include a blend of genes from ancient European domesticates, and hogs introduced from China during the 18th and 19th centuries (Giuffra et al. 2000). That introgression probably caused some substantial improvements in the hog population, but has helped to reduce genetic variation and move the population from its medieval structure to a more homogenized gene pool.

Gregory Cochran and I gave a short description of the history of cattle domestication and ongoing gene flow in our 2006 paper about introgression (Hawks and Cochran 2006). With four original cattle species in different parts of Eurasia, and the possibility of continued gene flow among imported breeds as well as the original progenitor species of European cattle, the aurochs (still known in early medieval times), the population history of European breeds may harbor a lot of complexity during the last 1000 years. Finding the medieval distribution of today's genes -- even if the only result is a mitochondrial DNA distribution -- might help us understand the distribution in which favored traits originated and were selected.

References:

Giuffra E, Kijas JMH, Amarger V, Carlborg Ö, Jeon J-T, Andersson L. 2000. The origin of the domestic pig: Independent domestication and subsequent introgression. Genetics 154:1785-1791.

Hawks J, Cochran G. 2006. Dynamics of adaptive introgression from archaic to modern humans. PaleoAnthropology 2006:101-115.

OK, so they've identified the body of Copernicus.

So, in the next stage, Swedish genetics expert Marie Allen analyzed DNA from a vertebrae, a tooth and femur bone and matched and compared it to that taken from two hairs retrieved from a book that the 16th-century Polish astronomer owned, which is kept at a library of Sweden's Uppsala University where Allen works.

"We collected four hairs and two of them are from the same individual as the bones," Allen said.

Which sort of makes you wonder about the other two hairs...

Anyway, naturally if we're going to start cloning extinct creatures, naturally we'll want to recreate the League of Extraordinary Scientists. Now, I don't know if Copernicus is going to be up to your standards; maybe you go for Newton, Einstein and Galileo first. But maybe if you want additional reinforcement that we aren't the center of the universe, you might build your Neandertal clone using a Copernican template. Although "Copernithal" sounds kind of like a pharmaceutical product of some kind.

I picked up a copy of Julian Huxley's Evolution: The Modern Synthesis this week at a book sale. It's funny -- the book was a review copy and bears the following bookplate:

To The Literary Editor:

Direct quotation in reviews is limited to 500 words or less unless special permission is given.

Well, I hope that the statute of limitations on the bookplate has passed, because I'm going to quote a lot more than 500 words out of this over the next few weeks.

I'll start with a passage from the first chapter. It brings to mind Mayr's famous comment about "bean bag genetics," but I find Huxley's approach at once more sympathetic and insightful about the nature of inheritance opposed to the way scientists describe inheritance:

In the early days of Mendelian research, phrases such as "in fowls, the character rose-comb is inherited as a Mendelian dominant" were current. So long as such phrases are recognized as mere convenient shorthand, they are harmless; but when they are taken to imply the actual genetic transmission of the characters, they are wholly incorrect.

Even as shorthand, they may mislead. To say that rose-comb is inherited as a dominant, even if we know that we mean the genetic factor for rose-comb, is likely to lead to what I may call the one-to-one or billiard-ball view of genetics. There are assumed to be a large number of characters in the organism, each one represented in a more or less invariable way by a particular factor or gene, or a combination of a few factors. This crude particulate view is a mere restatement of the preformation theory of development: granted the rose-comb factor, the rose-comb character, nice and clear-cut, will always appear. The rose-comb factor, it is true, is not regarded as a sub-microscopic replica of the actual rose-comb, but is taken to represent it by some form of unanalysed but inevitable correspondence.

The fallacy in this view is again revealed by the use of the difference method. In asserting that rose-comb is a dominant character, we are merely stating in a too abbreviated form the results of experiments to determine what constitutes the difference between fowls with rose-combs and fowls with single combs. In reality what is inherited as a Mendelian dominant is the gene in the rose-combed stock which differentiates it from the single-combed stock: we have no right to assert anything more as a result of our experiments than the existence of such a differential factor (Huxley 1943:19).

I try to emphasize this point whenever I introduce genetics: we know about inheritance because of our observations on organisms, not because we have traced the molecular effects of every gene. As when we interpret sounds into language, we depend on contrasts to see the effects of alleles. I am always amazed when we learn something new about these molecular mechanisms underlying observable phenotypes, because they manifest in so many different ways.

P. S. Yes, after all that, you deserve a picture of a rose-comb. But although Flickr has many, all are copyrighted, none Creative Commons. So, I won't republish, but here's a link to my favorite.

This is one doofy story:

Remains of rotten fish entrails have helped establish the precise dating of Pompeii's destruction, according to Italian researchers who have analyzed the town's last batch of garum, a pungent, fish-based seasoning.

OK, so far so good. But wait a minute! We have a perfectly good historical date from Pliny the Younger! August 24, 79 AD. There's not any chance that some kind of radiometric date is going to improve on that. So what's the deal?

Doubts about the date of the eruption emerged a couple of years ago when archaeologists discovered a coin which seemed to refer to the 15th imperiatorial acclamation of Titus, believed to have occurred on Sept. 7, 79 A.D.

OK, so the coin supposedly was later than the eruption, even though it was in the site. But wouldn't the simple explanation be that they struck the coins in advance of the event? Well, I guess there's also this:

"Unfortunately, that coin can't be taken as a dating evidence, since it is hardly readable. I myself agree with Ciarallo's dating of the eruption, even though I think that a bit of mystery remains. However, it is not so important whether the eruption occurred in August or in October," Teresa Giove, a coin expert at Naples' Archaeological Museum, told Discovery News.

So where does the fish sauce fit in?

"Pompeii's last batch of garum [fish sauce] was made with bougues, a fish that was cheap and easy to find on the market in those summer months. Still today, people living in this region make a modern version of garum, called "colatura di alici" or anchovy juice, in July when this fish abounds on the markets," Ciarallo said.

The eruption froze the sauce right at the moment when the fish was left to macerate. No batches of finished garum were found, since the liquid evaporated in the heat from the eruption.

"Since bogues abounded in July and early August and ancient Roman recipes recommend leaving the fish to macerate for no longer than a month, we can say that the eruption occurred in late August-early September, a date which is totally compatible with Pliny's account," Ciarallo said.

OK, so they don't keep the sauce macerating for more than a month. And September 7 is...less than a month after early August. Uhh...what was the story here? Why were we doubting Pliny again? I mean, I admire the knowledge that goes into this, and it's pretty cool to analyze ancient fish sauce, but this story just wasted my time!

Until this summer, I had only a vague idea of who Nikolai Vavilov was. I knew he had been Dobzhansky's mentor, and that like all Russian biologists, he had suffered at the hands of Lysenko. Otherwise, I had heard of Vavilov only in connection to an obscure quote from the introduction of Maynard Smith's Evolution and the Theory of Games:

Suppose for example, that only two kinds of wings could ever develop -- rectangular and triangular. Natural selection would probably favor the former in vultures and the latter in falcons. But if one asked 'Why are birds' wings the shapes they are?', the answer would have to be couched primarily in terms of developmental constraints. If, on the other hand, almost any shape of wing can develop, then the actual shape, down to its finest details, may be explicable in selective terms.

Biologists differ about which of these pictures is nearer the truth. My own position is intermediate. Clearly, not all variations are equally likely for a given species. This fact was well understood by Darwin, and was familiar to me when I was an undergraduate under the term 'Vavilov's law of homologous variation' (Maynard Smith 1982:7).

Well, so much the more for mystery. A historical footnote to be remembered in an argument with Stephen Jay Gould. So I filed it in the back of my mind, since this kind of developmental constraint hypothesis has become more and more important in human evolution during the past few years. It turns out that the traits that differentiate some hominid species are in many cases the same traits that have the most variation within species.

Anyway, it was enough to get my interest when Peter Pringle's new book, The Murder of Nikolai Vavilov, showed up in the local bookstore.