Dienekes has a report on some new studies of DNA in British skeletons dating from the first millennium A.D. I’m not sure what it all means, or how it relates to previous DNA studies, but I mention it in view of my previous post on Celts and Anglo-Saxons.

” “There’s just no correlation,” said Duke’s Wray, calling education and other environmental factors more important for intelligence than DNA anyway.”

Rikurzhen: Source

There is a new BRCA1 haplotype with a geographical distribution reminiscent of that seen in microcephalin and ASPM: the new variant is about 30k years old and considerably more common outside of sub-Saharan Africa (~55%) than inside (~20%) . BRCA1 has also been evolving unusually rapidly in the hominid lineage (like ASPM and microcephalin). It is suspected of having something to do with brain development, since it is highly expressed in neural stem cells and is functionally linked with microcephalin. Also, the high incident of BRCA1 mutations among the Ashkenazi Jews – as part of a complex of DNA-repair mutations – suggests that tweaking BRCA1 can affect cognition.

[Crossposted from GeneticFuture.org]

Scientists at Newcastle University have been given approval for new research aimed at combating a particular set of inherited human diseases: those that are passed on via mitochondrial DNA instead of the nuclear DNA most folks are familiar with. The trick? They’ll be creating human embryos that are the product of two mothers and one father. Here’s the background:

Nuclear DNA includes thousands of genes, and is given credit for making you who you are, and is in fact the only DNA considered when discussing the human “genome”. Mitochondrial DNA (MtDNA) only has 37 genes and doesn’t change much from individual to individual. However, that doesn’t mean that MtDNA isn’t capable of expressing diseases of its own.

So if you’re a mom who suffers from a mitochondrial disease, how do you keep from passing it on to your baby? According to the Newcastle researchers, here’s what you do: extract healthy ooplasm (including MtDNA) from a different mom’s egg cell and insert it into one of your own egg cells. Then fertilize it with the father’s sperm in the usual way (with glass rods and tubes and such) and presto! Healthy baby.

Trigger-finger ethics watchdogs suggest that you’ve just broken a new taboo — making an embryo that has two moms and one dad. Supporters would respond by saying that the nuclear DNA is the only “important” DNA, so who cares if the mitochondrial DNA comes from someone else?

Myself, I’m on the fence with this one. Most people would agree that there’s something ethically suspicious about making better babies by combining nuclear DNA from two moms. And while mitochondrial DNA doesn’t obviously code for things like blue eyes or long limbs, it does interact with nuclear DNA, working together for the expression and use of certain proteins. Will we discover some day that the rare and small differences found in MtDNA somehow have subtle (or profound) effects on the human phenotype — who we are and how we behave? If so, then mixing one mom’s DNA with the another mom’s MtDNA could lead us into ethically uncertain waters.

On the other hand, why not go for broke? Let’s use a surrogate mother for the womb too. Then we’ll have three mothers involved in the production of a newborn! Just imagine the positive impact such practices could have on profits on Mother’s Day… 🙂

[ Reference: BBC News ]

Researchers Say Human Brain Is Still Evolving. The crest of articles already seems enormous on Google News as I write. The papers are in the current issue of Science. I gotta run, but I assume other people on this blog will have comments, so I figured I’d act as the thin edge of the wedge….

Abstract:
Microcephalin, a Gene Regulating Brain Size, Continues to Evolve Adaptively in Humans Patrick D. Evans,1,2 Sandra L. Gilbert,1 Nitzan Mekel-Bobrov,1,2 Eric J. Vallender,1,2 Jeffrey R. Anderson,1 Leila M. Vaez-Azizi,1 Sarah A. Tishkoff,4 Richard R. Hudson,3 Bruce T. Lahn1* The gene Microcephalin (MCPH1) regulates brain size and has evolved under strong positive selection in the human evolutionary lineage. We show that one genetic variant of Microcephalin in modern humans, which arose 37,000 years ago, increased in frequency too rapidly to be compatible with neutral drift. This indicates that it has spread under strong positive selection, although the exact nature of the selection is unknown. The finding that an important brain gene has continued to evolve adaptively in anatomically modern humans suggests the ongoing evolutionary plasticity of the human brain. It also makes Microcephalin an attractive candidate locus for studying the genetics of human variation in brain-related phenotypes.

Abstract:
Ongoing Adaptive Evolution of ASPM, a Brain Size Determinant in Homo sapiens Nitzan Mekel-Bobrov,1,2 Sandra L. Gilbert,1 Patrick D. Evans,1,2 Eric J. Vallender,1,2 Jeffrey R. Anderson,1 Richard R. Hudson,3 Sarah A. Tishkoff,4 Bruce T. Lahn1* The gene ASPM (abnormal spindle-like microcephaly associated) is a specific regulator of brain size, and its evolution in the lineage leading to Homo sapiens was driven by strong positive selection. Here, we show that one genetic variant of ASPM in humans arose merely about 5800 years ago and has since swept to high frequency under strong positive selection. These findings, especially the remarkably young age of the positively selected variant, suggest that the human brain is still undergoing rapid adaptive evolution.

Addendum, Rikurzhen:

Q: are there phenotypes (e.g. brain size or IQ) associated with these alleles?
A: no, these alleles have not been tested; but loss of function alleles of these genes affect brain size

Also note that there are almost certainly hundreds of QTLs for IQ, and previous attempts to find linkage or assocation have been not especially fruitful — largely because of low statistical power. However, because there is such a strong selective signature on these alleles, there is likely to be a pheotypic effect, albeit likely a small one. From the Microcephalin paper:

The specific function of Microcephalin in brain development makes it likely that selection has operated on the brain. Yet, it remains formally possible that an unrecognized function of Microcephalin outside of the brain is actually the substrate of selection. If selection indeed acted on a brain-related phenotype, there could be several possibilities, including brain size, cognition, personality, motor control, or susceptibility to neurological and/or psychiatric diseases. We hypothesize that D and non-D haplotypes have different effects on the proliferation of neural progenitor cells, which in turn leads to different phenotypic outcomes of the brain visible to selection.

Jason M. adds: The files have been added to the GNXP files section. Not to be missed! Also here’s my thread over on MetaFilter.

Update from Razib: Of course you should read what John Hawks has to say. Andrew advises caution. Slasdhot has a thread (I don’t see anything below a mod score of 4 but there still isn’t much to see…though John popped up in there). Here is a technorati query you might want to keep track of.

TangoMan adds: Maps below the fold.

Click on maps for the larger versions.

Does anyone know, statistically speaking, what sort of product the public schools are producing… according to their own advocates… after excluding 8% of the student body from testing for various reasons?

Here are the actual numbers. To some degree they speak for themselves, but here are the highlights. The top 10% of 4th grade students equal or outperform the bottom 25% (really over 45% after accounting for children excluded from the test and children who dropped out of high school) of 12th grade students, and the top 25% of students outperform the bottom 10% (really over 30% for reasons given above)! For your reference, roughly 25% of the US population gets a college degree, so the average person who will get a college degree has better math ability and reading comprehension in 4th grade than the bottom 4th of the population will have after 8 more years of schooling supposedly teaches them these subjects!

This is all the more remarkable in light of the antiquated concept of IQ as a quotient. Around the mean, this concept is predictively accurate for the most part. From the quotient definition of IQ we can infer that there are many cognitive tasks which are not taught in school in which the 10th percentile 14 year old substantially outperforms the 90th percentile 9 year old. In other words, performance in the subjects which are “taught” improves less than would be expected simply from mental maturation, or at least less than performance in subjects that are not taught.

Straight from Sweden to a computer near you: The Human Protein Atlas. For all of you people out there who are into proteins and stuff.

The Human Protein Atlas

Sex-contingent face after-effects suggest distinct neural populations code male and female faces. Well, the link was titled “Human brain favors familiar faces.” Not ground-breaking research, but I’ve put it in the files.

The Scientist recently did an interview with Bruce Lahn. I got it out of the google cache (it is premium now) so I cut & pasted it below in case something happens to that….

Rebel with a Lab

For Bruce Lahn, an interest in human genetics has roots in Chinese protests

By Karen Hopkin

Bruce Lahn has always been something of a rebel. As an undergraduate at Beijing University in the late-1980s, Lahn was a ringleader in the first wave of student prodemocracy protests. “I was fiercely opposed to the communist ideology,” he says. “I just didn’t want to be told what to do, especially if it didn’t come with a reason.” These early rallies set the stage for the huge demonstrations that would culminate in the infamous crackdown in Tiananmen Square.

Although Lahn had transferred to Harvard University by the time the government sent in the tanks, his disgust with the system helped shape his scientific career. “I had this idea that the problems with China, in addition to being social, might also have a genetic root.” Indeed, all human behavior – our tendency toward violence as well as our capacity for kindness – must, to some extent, be encoded in our DNA. So Lahn decided to study human genetics. “I was attracted by the idea of understanding human behavior, especially how it relates to society, in a deeper way.”

In that effort to understand human behavior, Lahn, now a Howard Hughes Medical Institute (HHMI) investigator at the University of Chicago, is searching for the genes that make the human brain unique. By scanning the sequences of some 200 brain-related genes from mice, rats, macaques, and humans, Lahn and his colleagues have turned up a handful of genes that appear to have evolved very rapidly in the human lineage. Most are involved in brain development, suggesting that bigger, better-wired brains might have given our ancestors a selective advantage. These genes, Lahn hopes, might give us a handle on what makes us human.

“Not many people start out their careers saying they’re going to study the molecular basis of humanness,” says Ajit Varki of the University of California, San Diego. “That’s what I find interesting about Bruce: he’s decided to go for it. We need more people like him in the field.”

MEN IN GENES

Before pouncing on what makes humans human, Lahn focused his attention on what makes men men. As a graduate student in HHMI investigator David Page’s lab at MIT, Lahn characterized a couple of dozen genes that were unique to the Y chromosome. “One day he just decided he was going to clone all the genes on the Y chromosome,” says Karin Jegalian, a former labmate who is now a freelance writer. “He realized that with a little bit of PCR and a few sequencing machines, he could do it. And he went ahead and got it done.” The feat provided insight into the evolution of the Y, which started life as a standard-issue chromosome that shrunk and became specialized to govern sperm production and the development of other male-related traits.

The experience gave Lahn an entrée into human genetics and whetted his appetite for combining molecular biology with an appreciation of evolution. “I wanted to bring evolution to bear on molecular biology and I hoped that a synergy of the two would allow me to do things that people in either camp couldn’t do,” he says. Take, for example, his work on the potential “humanness genes.” Now that Lahn and his lab have identified genes that have undergone accelerated evolution in humans, they’ll investigate how the variants unique to humans contribute to building better brains.

“We’re getting to the point where we can start taking the next step to look at function — to find out how these changes do what they do,” says grad student Nitzan Mekel-Bobrov.

“Tying molecular evolution to function is a big goal,” says Steve Dorus of the University of Bath, Lahn’s first PhD student. “But Bruce is a go-getter with boundless energy. He’s very tenacious and not afraid of tackling any kind of project.” Even ones that involve probing the evolutionary changes that might have helped shape human behavior.

“Bruce is very careful to stick to the science, stick to the facts,” says Mekel-Bobrov, because not everyone is comfortable with comparisons between humans and other primates, particularly comparisons that involve gene sequences. “When you align the chimp sequence and the human sequence you’re immediately struck by the similarity between the two: base after base, the sequences are the same. It can be very jarring,” he says. “If we’re so similar, what is it that makes us special?”

IT’S IN OUR MINDS

To Lahn’s mind, the brain seemed a good place to start. At the time, says Lahn, “the human was sequenced, the mouse was being sequenced, the rat was beginning to be sequenced, and monkey wasn’t even on the drawing board. Given that we were just one small lab, we couldn’t sequence the whole genome of any species.” So he targeted the brain; a move Varki likens to the outlaw Willie Sutton saying that he robbed banks because “that’s where the money is.”

i”Bruce is going for the brain; he’s going where the action is and finding things out. And that’s great,” says Varki. But Varki cautions that evolutionary changes don’t occur in isolation and that a narrow focus on the brain, perhaps the most complex and difficult organ to probe, might cause the researchers to overlook clues to our humanness that are more accessible. For example, Varki notes, the tissue that shows the most obvious difference between humans and chimps actually falls just below the shoulders: the breast. In female chimps the breasts do not become very noticeable until the animal is pregnant. “It may be that the genes that are involved in that difference in the breast are the same ones that are responsible for some of the differences in brain development,” he postulates.

So far, Lahn’s approach appears to be paying off. Over the past year, he and his team have described their findings on human brain evolution in a flurry of papers in Human Molecular Genetics, Cell, and Science. The author list for each publication bears the names of a good percentage of the people in Lahn’s lab.

“These projects are large: no single person could do any of them,” says Jerry Wyckoff of the University of Missouri, Kansas City, a former postdoc. Most require the expertise of molecular biologists, geneticists, bioinformaticists, and even anthropologists. Fortunately, Lahn has been able to gather this variety of talents under one roof. “The thing that Bruce is really good at – his special talent, his mutant skill – is finding good people,” says Wyckoff. “Bruce has great ideas. But without the people to play out those ideas, he wouldn’t get very far. He’s able to assemble the resources and people to take his ideas and run with them. It’s why he’s a successful scientist.”

OTHER ‘CRAZY’ IDEAS

Chasing down candidate humanness genes is not Lahn’s only big idea. He also maintains an active research program on stem cell biology. Just as Lahn wishes to understand what makes humans human, he also hopes to unravel why stem cells are stem cells. “Why are they capable of many different fates, whereas differentiated cells are stuck with their particular characteristics?” he muses. Lahn is conducting some of this research in China, in a stem cell center that he founded at Sun Yat-sen University. “There, it’s easier to access materials, eggs, embryos, and fetal tissue. And we can do certain manipulations that would be hard to do here,” he says. “The idea is to leverage the advantages, both in terms
of social permissiveness and the cost of certain reagents.”

At Sun Yat-sen University’s Center for Stem Cell Biology and Tissue Engineering, Lahn and his colleagues are working to derive human and primate stem cell lines from embryos and fetuses with a variety of genetic backgrounds. Like many researchers, Lahn hopes to learn how to coax stem cells to differentiate into specific cell types, perhaps for eventual use therapeutically to replenish or repair tissues in patients with blood disorders or neurodegenerative disease.

For Lahn, returning to China is more than a convenience. It’s his way of doing something to make China a better place — more like the place he was thinking about when he hung those first rally posters in the halls of Beijing University. “I believe the way to develop China is not to overthrow the communist government. The costs of that, in terms of violence and the ensuing chaos, may actually be too high a price to pay,” he says. “Instead I want to help China develop scientifically, by promoting the exchange of information, the exchange of people, the flow of ideas. And I’d like to pursue research directions that will put China on the map [and] make China a leader in the world instead of having the country play a me-too, catch-up role,” Lahn explains.

“I also have a number of more crazy ideas,” he adds: growing human organs in monkeys, for example. “People talk of stem cell biology as if someday we’ll be able to grow organs in a Petri dish,” notes Lahn. “That’s never going to happen. Certainly not in my lifetime.” The way he sees it, the best way to grow an organ, particularly a complex organ such as heart or liver, would be to implant stem cells into a suitable host and then allow those cells to form the desired tissue in vivo, in the animal. For instance, to produce a liver that’s suitable for transplant, Lahn imagines first generating a transgenic monkey whose own liver development fails early on. Researchers could then seed that animal with human stem cells that could take root and give rise to a liver that’s almost entirely human. Lahn and his colleagues are currently investigating whether stem cells from one type of rodent can survive and differentiate in another.

“He’s been talking about this stuff since graduate school,” says Jegalian: stem cell biology and what makes us human. “At the time it sounded pretty kooky. But it’s cool that he’s still thinking about it, has published papers on it, and is even going back to China to do it.”

Of course Lahn hasn’t entirely abandoned the rebellious ways he first expressed in China. “I will probably continue to work on problems that are off the beaten path [and] approach science in a way that’s less conventional in the hopes of finding something that’s a little more exciting, that might bring major insights or upset conventions,” he says. “I guess I still have a little bit of revolutionary spirit in me — even though now I’m more of an evolutionary guy.”

Genes in Conflict is a book coming out this November by Robert Trivers and Austin Burt. You can read a full text of a paper titled Theory of genomic imprinting conflict in social insects that Trivers and Burt coauthored, I suspect it gives one a flavor of what is to come. Classic “logic with fractions.”