Breadth-first search

When I complain about some egregious piece of research,  particularly those that are in some sense cross-disciplinary, I often feel that that just knowing more would solve the problem. If Roland Fryer or Oded Galor understood genetics, they wouldn’t make these silly mistakes. If Qian and Nix understood genetics or American post-Civil War history, they would never have written that awful paper about massive passing.  Or if paleoanthropologists and population geneticists had learned about mammalian hybrids, they would have been open to the idea of Neanderthal introgression.

But that really amounts to a demand that people learn about five times as much in college and grad school as they actually do.  It’s not going to happen.  Or, perhaps, find a systematic and effective way of collaborating with people outside their discipline without having their heads shaved. That doesn’t sound too likely either.

 

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Dogs and Men

Razib Khan talks about a new article that suggests that dogs were domesticated quite a long time ago, perhaps more than 35,000 years ago, well before the last glacial maximum.

We know that dogs have adapted to life with people, have changed in many ways.

I wonder how humans adapted to dogs.  If they were like modern pariah dogs, hanging around the village and eating garbage, doesn’t seem that they would have been that influential. But if used in hunting, they could have been very important, especially back in the Ice Age – and if they were that important, the partnership might have generated significant selective pressures in humans.

Parenthetically, there was an article a few years back that claimed that dogs had probably been domesticated for ~100,000 years, while most other estimates were around 14,000 years. Obviously there was a simple way to reconcile those two numbers.

 

 

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One more time

One of our local error sources suggested that it would be impossible to rebuild technical civilization, once fallen. Now if every human were dead I’d agree, but in most other scenarios it wouldn’t be particularly difficult, assuming that the survivors were no more silly and fractious than people are today.  So assume a mild disaster, something like the effect of myxomatosis on the rabbits of Australia, or perhaps toe-to-toe nuclear combat with the Russkis – ~90%  casualties worldwide.

Describe the recovery process, why it’s feasible and in fact almost easy. Show your work.

There’s no reason that I should have to explain everything.

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Measles and immunological amnesia

A new paper in Science , by Michael Mina et al,  strongly suggests that measles messes up your immunological defenses for two or three years. This is the likely explanation for the fact that measles inoculation causes much greater decreases in child morbidity and mortality than you’d expect from preventing the deaths directly due to measles infection. The thought is that measles whacks the cells that carry immunological memory, leaving the kid ripe for reinfections.  I think there can be a similar effect with anti-cancer chemotherapy.

If correct, this means that measles is much nastier than previously thought. It must have played a significant role in the demographic collapse of long-isolated peoples (such as the Amerindians). Its advent may have played a role in the population decrease associated with the decline of the Classical world.  Even though it is relatively new (having split off from rinderpest a couple of thousand years ago) strong selection for resistance may have  favored some fairly expensive genetic defenses (something like sickle-cell) in Eurasian populations.

We already know of quite a few complex side effects of infectious disease, such the different kind of immunosuppression we see with AIDs, Burkitt’s lymphoma hitting kids with severe Epstein-Barr infections followed by malaria, acute dengue fever that requires a previous infection by a different strain of dengue, etc: there may well be other important interactions and side effects, news of which has not yet come to Harvard.

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Eugenics, Ready or Not

There is an excellent essay about eugenics, genetic manipulation, and technology by Frank Salter here in the Australian webzine Quadrant and reprinted here. The essay is nearly free of the incessant hand wringing that pervades most journalism about the topic. Instead the treatment is thorough, wide ranging, and sensible—journalism for intelligent adults. Science writers will blush with shame as they read this essay.

The links above are to part one of the article: part two is promised to appear “shortly”.

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SNP confusion

A single nucleotide polymorphism is a nucleotide that is variable – not everyone has the same one at that site.  To be more precise, it’s one that has significant variation – at least a few percent of people (in the population you’re studying) have something other than the most common nucleotide at that site.  Generally, the most common nucleotide is the ancestral one.

You see such a variable site every few hundred nucleotides.  Checking out the SNPs is less informative than sequencing the whole genome, but it’s much easier.

Most of these  SNPs are in neutral parts of the genome and don’t do anything, one way or the other. If you’re investigating ancient population splits and such, this is useful, easier to analyze: neutral means unloaded dice, adaptive evolution means dice loaded in unpredictable ways.

In order to pick a set of SNPs, you look at members of some population and see which sites in the genome are sufficiently variable.  They may still be good SNPs in another population, as  long as that population is sufficiently similar – that is, shares most of the same drift history.

On the other hand, if the two populations have been separated for a long, long time,  they won’t have the same SNPS, at least not entirely: sites that are variable in population 1, the population  you used to pick your SNPS, may be fixed in the second population, while sites that are essentially fixed in the first population may be SNPs in population 2.  The long the separation, the more this happens.

Some years ago, some friends of mine looked at how ancestral (on average) SNPs were in different populations.

chimps

The average degree of ancestralness was almost exactly the same in Eurasian populations, but was noticeably higher in typical farming populations of sub-Saharan Africa such as the Yoruba, and was higher still in African hunter-gatherers such as the Pygmies and Bushmen.

We found this puzzling, and it took a while to figure it out. The root cause turned out to be  that the drift histories of Eurasians were pretty much all the same, but the drift history of the Yoruba was different enough that they had somewhat different SNPs than Eurasians, while the Bushmen & Pygmies had split off even earlier and had an even more different drift history.

This point is technical, even boring once you figure out the answer, but add some misunderstanding&ideology  and the story gets hilarious.

Now this following story I mostly got second hand, so take it with a grain of salt. But I think it’s basically accurate.

You see, somewhat earlier, people working with the same datasets noticed the same phenomenon, and instead of puzzling through it, they panicked.  They thought that those higher levels of ancestrality in Africans meant that Africans were genetically closer to chimpanzees  than other humans – which is not the case.  One of them came up with the memorable phrase ‘chimp index‘ for average ancestrality.

Around the same time, there was a lot of odd activity at NIH, and I strongly suspect that activity was connected to the chimp index crisis. Even at the time, before we looked at this problem, I thought that something strange was going on. They called a special meeting, where those receiving NIH grants in human genetics were told to be careful to make sure that reporters didn’t get the wrong idea about genetic differences between populations.  Marc Feldman proposed organizing ‘flying squads’ to rush out and counteract such misunderstandings – which inspired me to design a shoulder patch for those flying squads:

REDgreenBLACK-3

Eventually someone who knew some theory must have figured it out and explained it, which would have calmed things down.  But for a while, the powers that be at NIH must have been shitting in their pants.  How awful.

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The Old Race

That puzzling variant of PLK4, that increases the miscarriage rate,  is very widespread, moderately common in almost all population – but it’s rare in Bushmen (frequency of 1 in 38 among the  Ju’/hoansi) and Pygmies,  enough to you suspect that it wasn’t there at all before the Bantu recently admixed with both groups.

The Bushmen (and probably African Pygmies as well)  apparently split off earlier than any other human population, something like 200,000 years ago. Some Bushmen among the Ju’/hoansi, show low or even zero admixture with other groups.  How they managed to have so little gene flow with other Africans for such a long time is a mystery to me, but that’s what the stats say.  There is more genetic distance between the Bushmen and Bantu than there is between Bantu and Koreans.

This long separation doesn’t necessarily mean that Bushmen ave the most divergent phenotypes (although thinking about it, they probably are, what with steatopygia , the tablier egyptienne, etc)  – strength and direction of selection are important, not just time.  But all else equal, more time allows greater changes.

This doesn’t mean that the Bushmen are what early homo sap was like – they’ve been evolving too – but we ought to be able to learn quite a bit about changes over the past couple of hundred thousand years by investigating  genetic differences between the Bushmen and everybody else.  For example, 200 k years ago, our ancestors didn’t have what it takes to out-compete Neanderthals and other archaics on their home grounds, judging by the fact that they didn’t manage it back then.  By 40k years ago we could and did – but that isn’t necessarily the case for Bushmen, a separate branch. Although, since Bushmen and Pygmies seem to have picked up a few percent of their genome from some very divergent group of archaic humans, perhaps they too developed the ability to kick archaic ass. But we don’t know if they did it in the same way, and it probably happened in fairly familiar African environments, instead of ice age Eurasia.

By the way, I have a very funny story about Bushman genetics, but there are not enough electrons in this margin.

 

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