The Pith: Natural selection is a quick & dirty operator. When subject to novel environments it can react rapidly, bringing both the good and the bad. The key toward successful adaptation is not perfection, but being better than the alternatives. This may mean that many contemporary diseases are side effects of past evolutionary genetic compromises.
The above is a figure from a recent paper which just came out in Molecular Biology and Evolution, Crohn’s disease and genetic hitchhiking at IBD5. You probably have heard about Crohn’s disease before, there are hundreds of thousands of Americans afflicted with it. It’s an inflammatory bowel ailment, and it can be debilitating even to very young people. The prevalence also varies quite a bit by population. Why? It could be something in the environment (e.g., different diet) or genetic predisposition, or some combination. What the figure above purports to illustrate is the correlation between Crohn’s disease and the expansion of the agricultural lifestyle.
But don’t get overexcited Paleos! There are many moving parts to this story, and I need to back up to the beginning. The tens of thousands of genes which you inherited from your parents are embedded within the genome and aligned in a set of sequences, one after the other. On the one hand for the purposes of conceptualizing evolutionary dynamics, such as natural selection or random genetic drift, focusing on a single gene is useful. It has power to illustrate some basic and elementary principles. But sometimes you need to take a more synoptic view, and look at genes in their broader context. In this post I’ll avoid molecular or statistical epistasis, gene-gene interaction. Rather, let’s just consider the static landscape of the genome, where genes are physical concrete entities which are embedded in a particular spatial relationship to other genes, upstream or downstream in the genetic code. These physical or statistical associations of genes can form a de facto supergene through linkage, and their variants combine to form haplotypes, sequences of markers across small stretches of the genome. But recall that these associations are counter-balanced by genetic recombination, which tears apart physical sequences and sows them to the opposite DNA strand.
Ewen Callaway has a good survey of what’s been going down in ancient human genomics over the past year in Nature, Ancient DNA reveals secrets of human history. It’s not paywalled, so read the whole thing. Most of it won’t be too surprising for close readers of this weblog, but this part is new:
By comparing individual DNA letters in multiple modern human genomes with those in the Neanderthal genome, the date of that interbreeding has now been pinned down to 65,000–90,000 years ago. Montgomery Slatkin and Anna-Sapfo Malaspinas, theoretical geneticists from the University of California, Berkeley, presented the finding at the Society for Molecular Biology and Evolution meeting in Kyoto, Japan, held on 26–30 July.
Slatkin says that their result agrees with another study presented at the meeting that came from the group of David Reich, a geneticist at Harvard Medical School in Boston, Massachusetts, who was involved in sequencing both the Neanderthal and Denisova genomes. The dates also mesh with archaeological finds bookending early human migrations out of Africa to between about 50,000 and 100,000 years ago. Reich’s team is now developing tools to find signs of more recent interbreeding that might have occurred after humans arrived in Asia and Europe.
Remember that the Neandertal admixture seems present in all non-Africans. That pegs the admixture event very early, before the diversification of modern human populations. I wouldn’t put too much stock in any one value presented at a conference with a large confidence interval. From what I hear there will be much more on statistical genetic inferences of admixture timing over the next year, but if there’s one thing that the enormous yield from genomes constructed from ancient DNA has convinced me is that we should be really cautious of results which we can’t cross-check easily because of their time depth. I read a lot of papers by high-powered teams before 2010 on how the genomic evidence implied no admixture between modern human and archaic lineages, and gave them great weight. There’s only so much power in working back to the past from the present.
As some of you know, I have a problem. An addiction that is. For most of the year I stock up on fresh habanero pepper. Usually I try to limit myself to 1-2 peppers per meal…but when not in the company of others who may civilize me I can lose control and eat more than half a dozen in a sitting. After the first few peppers they just don’t taste as spicy, and I suppose psychologically I am under the illusion that enough peppers will bring back the pleasure high of a few moments earlier. I developed this habit not through cultural inculcation. Rather, when I went off to college and no one supervised me I began to eat more and more peppers, and developed an extremely high threshold of tolerance. By the end of college I began to raid my parents’ thai peppers at home to the point where they complained that I always left their stock depleted before going back to school. At this point I can drink tabasco sauce like gatorade.
But the different parts of the gastrointestinal system adapt differently. When I “habanero gorge” I develop extreme pain in my bowels in a few hours, and of course there are issues the next day. Over the years I’ve poked around the literature on possible correlations between pepper consumption and stomach cancer, or the anti-pathogenic properties of peppers. I’m pretty sure I’m well beyond the limit of normal consumption in any of these studies.
My primary motivation in consuming peppers is pure hedonism, as can be attested by the fact that my consumption is constrained by the presence of others. But there are clear social consequences to eating extremely spicy food. People take notice when you pile on crushed read peppers onto pizza, or pull out a habanero at In-N-Out Burger. At nice restaurants you sometimes get well known for being the guy who likes the habanero paste lathered onto his beef, to the point where new servers might drop by to gawk. There can be a clear element of social signalling in consuming very spicy foods. In short, people can think you are a “badass.” Of course actually I’m a cheerful and self-effacing individual! (granted, with a casual tendency to verbally bludgeon people)
Last year some readers forwarded me a strange story about Hitler’s “Jewish genes”. I didn’t think much of it, but enough people asked that I thought I should at least address the story (or lack of one). Today something similar is happening with the Y chromosomal lineage of the boy pharaoh Tutankhamun. A Swiss company is claiming that by examining the set of markers divulged on a BBC special on Tut’s genetics they’ve established a high likelihood that he was of the R1b1a2 haplogroup. The firm making these claims has a history of sensationalism. That should tune our prior expectations a great deal. One of the researchers who did the original genetic analysis rejects the claims out of hand. On the basis of science then that’s where it ends.
But this actually is an interesting story of meta-science, of the media reaction to genetic results (or genetic inferences, tenuous though they may be), and their intersection with politics. One of the more ridiculous headlines I saw was this from CTV: King Tut may have been more European than Egyptian. I can see where they’re coming from, the haplogroup which Tut may have been a member of is present at over ~50% frequency in Western Europe, and ~1% in Egyptians. But this is just a single locus, a marker which traces the paternal lineage of an individual (assuming they’re male). To illustrate the obvious fallacy of this logic, recall that Dr. Daniel MacArthur is of the same haplogroup as I am, R1a1a. Does this imply that I am “more Scottish than Bengali”? Not really. In terms of total genome variation I’m South Asian, and Dr. MacArthur is Northwest European. Our paternal lineage is just one slice. Secondarily, why can’t we formulate it so that Dr. MacArthur is “more Bengali than Scottish”? There are more Bengalis than Scots by about 1 order of magnitude.
Likely presidential candidate Rick Perry’s college transcript at Texas A & AM has been published. Here are the highlights:
…In his freshman and sophomore year, Perry struggled with core science classes, earning D’s in several organic chemistry classes and C’s in general chemistry and physics.
But after Perry switched his major at the beginning of his fall semester in 1970, his grades didn’t improve. Perry got a C in Reproduction in Farm Animals, a C in genetics, a D in Feeds & Feeding, a C in Sheep & Angora Goat Production and two C’s in animal breeding classes.
Many of Perry’s other classes involved military education. Perry has previously credited his time in the A&M Corps of Cadets with giving him the necessary discipline to complete school.
Perry got two C’s in Development of Air Power and took four levels of World Military Systems, earning two C’s, a B and an A. The A was one of only two Perry earned at college — the other was for a class called Improv. of Learning.
The future governor only took one political science class while he was in school — American National Government, for which he earned a B. Other classes outside of Perry’s major included Shakespeare and Writing for Professional Men, which earned him two D’s.
Perry took two summer sessions before his senior year but still needed two more after the rest of his class graduated to complete a degree. He graduated in August of 1972.
Early in his career the famed evolutionary biologist William D. Hamilton had a strong interest in eugenics. In his autobiographical collection of papers Hamilton admits that he suspects these tendencies were the reason for the suspicion he aroused in some of the more senior scientists in Britain after World War II. But Hamilton later also admits that his earlier enthusiasms for social engineering through selection for “good traits” may have been wrong-headed, insofar as the selection pressures of evolution are protean, and what may be adaptive perfection in one age may be doom in another (or, in the world of international migration, you can substitute place for time). This does not mean that Hamilton abandoned his worry about increased “genetic load” in the human population (deleterious mutations accumulating in the human gene pool because the “unfit” now live and breed thanks to modern medicine). It is simply that such ideas and concerns can’t be easily reduced into simple formulas and maxims, because evolutionary processes can vary in their implications over time and place.
Over at Genetic Future Dr. Daniel MacArthur has a measured response to a Nature commentary by David Goldstein, Growth of genome screening needs debate. As Dr. MacArthur notes an excessive portion of Goldstein’s piece is taken up with inferences derived from assuming that the model of rare variants causing most diseases is correct, when that is an issue currently in scientific contention (and this is a debate where Goldstein is a primary player on one side). But the last two paragraphs of the piece is where the real action is, no matter the details of genetic architecture of diseases:
One potential problem with this is that numerous genetic risk factors will have diverse and unexpected effects — sometimes causing disease, sometimes being harmless and sometimes perhaps being associated with behaviours or characteristics that society deems positive. Even for simpler Mendelian diseases, up to 30% of the mutations originally termed pathogenic have turned out to be apparently harmless…Wholesale elimination of variants associated with disease could end up influencing unexpected traits — increasing the vulnerability of populations to infectious diseases, for instance, or depleting people’s creativity.
There are no clear-cut answers to the questions of what should be screened for and to what end, but we must at least begin the debate.
Carl pointed me to this really strange interview in New Scientist, Susan Greenfield: Living online is changing our brains. If you removed it from the New Scientist website and put it on the The Onion it wouldn’t really need much editing. Some of the things Susan Greenfield says make you scratch your head. First paragraph:
You think that digital technology is having an impact on our brains. How do you respond to those who say there’s no evidence for this?
When people say there is no evidence, you can turn that back and say, what kind of evidence would you imagine there would be? Are we going to have to wait for 20 years and see that people are different from previous generations? Sometimes you can’t just go into a lab and get the evidence overnight. I think there are enough pointers that we should be talking about this rather than stressing about not being able to replicate things in a lab instantly.
Happy-slapping? Seriously? That was so mid-2000s. It’s going to be really hard to escape the oncoming rush of the “wall of information” in the near future. If it drives our world insane, there are always the residents of North Sentinel Island.
I was alerted to Samuel’s Arbesman’s new paper, The Life-Spans of Empires, by the fact that he pointed to his research on his weblog. Interestingly I’m not the only one who was interested, as after I pointed to it on my link round up a few people asked if they could get a copy of the paper (yes, I almost always send papers if I have access). Luckily it’s a nicely elegant piece of work, basically quantifying what we’ve already probably known qualitatively. There isn’t that great of a value-add to quantification as such, but with a mathematical understanding of a topic one can engage in an algebra of mental manipulations so as to construct models with which one can project other facts. Quantitative information is often an excellent way to generate “free information” from theoretical models. The figure above is the primary result of the paper. Basically Arbesman took a data set which was laying around which measured the lengths of various empires (N = 41), and showed that the rise and fall of these political entities tends to follow an exponential distribution: e−λt . This is an incredibly elegant summation of what we know qualitatively: some empires last a long time, but most do not.
A few years ago the president of Iran, Mahmoud Ahmadinejad, asserted that his nation did not have gays as they did in the West. What Ahmadinejad seems to have meant is that a public gay identity does not exist in Iran. He has to be aware that homosexual behavior is not unknown in his nation. More generally Ahmadinejad’s comments brought up the issue of men having sex with men throughout the Middle East before marriage. This is a taboo topic in much of the region, so getting good quantitative data seems pretty much impossible. But today PLoS Medicine came out with a paper with a result which suggests that the anecdotes of relatively widespread homosexual behavior in the Middle East are not totally unfounded or unrepresentative (the journalist Hugh Pope has indicated that Middle Eastern men have sometimes assumed he would naturally be open to sexual propositions because he was a Westerner. He grew a mustache to discourage such inquiries) . The paper is about HIV, Are HIV Epidemics among Men Who Have Sex with Men Emerging in the Middle East and North Africa?: A Systematic Review and Data Synthesis. Here’s the figure which jumped out at me:
A few readers reminded me of the recent Rachel Caspari article in Scientific American, The Evolution of Grandparents. It’s actually based on her earlier research, published in PNAS in 2004, Older age becomes common late in human evolution. I was already pointed to this paper by Milford Wolpoff, who seems to be of the opinion this is a very underappreciated dynamic in our species’ history (note: he’s married to Caspari). And Wolpoff sent me a copy of the Scientific American article too, so it’s been in my “to read” folder for a bit.
Honestly it’s a lot more persuasive than the scientific paper because it’s so non-technical. It really makes me appreciate the power of science communication. I don’t know anything about the analysis of dental remains, so I really hummed along through a lot of the paper with minimal comprehension. With the article Caspari could present her results and interpretation more cleanly.
The major finding in the PNAS finding, which is reported in the Scientific American article, is the ratio of parents to grandparents in a total sample of ~750 remains separated by population class varies a great deal. Parents here means those who are 15-30 years old in age, and grandparents are those who are 30+ years in age. The major qualifier here is obviously potential, but that’s a side issue. What the authors found in their sample was quite striking: notice the huge qualitative shift when you move to a population set of Upper Paleolithic behaviorally modern humans (less than 50,000 years before the present). In contrast, the European Neandertals much more resemble the larger collection of archaic Homo (most of which would presumably have been termed “archaic H. sapiens” in the past because they span 50 to 150,000 years B.P.). This still leaves the question of whether this is nature or nurture is left hanging.
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A few people have pointed me to the recent paper in Science, Tenfold Population Increase in Western Europe at the Neandertal–to–Modern Human Transition. The basic result is obvious, and not totally revolutionary: anatomically modern humans may simply have demographically absorbed the Neandertals (the word “absorbed” has many connotations here obviously). The results are clear in this figure:
This is not surprising, even though I have only a glancing familiarity with the guts of paleontology I was aware that there’s a lot of inferential evidence that Neandertals were not as efficient at extracting resources from any given piece of territory as modern humans. In The Dawn of Human Culture the paleoanthropologist Richard Klein offered a straightforward biological explanation for why and how the neo-African populations so rapidly marginalized Neandertals: some sort of macromutation which allowed for language and so the protean flexibility of human culture.
Last week I begged for a Malagasy genotype. I didn’t quite get that, but I got the second best thing: a part Malagasy-genotype. I decided to take it for a spin.
But first some preliminaries. Here’s what we know about this individual (or what this individual knows):
- 25% French (paternal grandfather)
- 18.75% West African? 6.25% French? (paternal grandmother French Antilles)
- 19% Indian Muslim Bohras from Bombay + 6.25% Malagas, Sakalava tribe, royal family of Mahajanga (maternal grand -father)
- 25% Malagasy (Sakalava, maternal grandmother mtDNA haplogroup M23)
This is a very mixed individual in terms of ancestry. As for the Malagasy people, we know both a lot and a little about them. They’re a hybrid population, more or less, of Austronesians with a very close connection to the to the Dayaks of southern Borneo. I have hypothesized that these Austronesians were part of a circum-Indian ocean trading network which was marginalized by the rise of Islam in the second half of the first millennium. Such an early date would explain why the Malagasy seem to have been only lightly touched by Indic cultural influences, let alone Islamic ones. There is also the African component to their ancestry, which is more prominent in the lowland populations to the west of the island of Madagascar. The Sakalava are a somewhat more African group (as opposed to the Merina of the eastern highlands, who are more Austronesian).
Below are some results from ADMIXTURE and PCA generated with EIGENSOFT. Most of the PCA plots were not too useful, because I didn’t fine-tune the populations ahead of time too much (this is a first pass), so I didn’t post them. The ADMIXTURE runs are those which seem highly informative to me. There were three data sets into which I merged the part-Malagasy individual:
- #1, A Southeast Asian focused one, using mostly the Pan-Asian Consortium populations
- #2, An Asian focused data set which used the HGDP
- #3, An African focused data set which used the Henn et al. populations as well as some HGDP ones
A 5 star rating is good. The sample size is not too large in relation to previous books, but I think we can conclude that this is more in keeping with the perception of relative mediocrity of book 4, than the epic virtuosity of the first three in the series. I have also now read A Dance with Dragons, and here are my impressions (no specific spoilers, though I’m going to talk about the general tenor)….