According to Wikipedia:

“Structural genomics seeks to describe the three-dimensional structure of every protein encoded by a given genome.”

But what does this mean?

The first time I heard about structural genomics it had a much better name, and a more limited scope: it was being called the ‘human protein structure project’. It was 1996 and the human genome project was well underway and it had really caught the public’s imagination. Looking at the proteins encoded by these genes seemed the obvious next step.

I was a PhD student attending a summer school course and we were celebrating the end of the week with a formal meal. David Blow, a renowned scientist who was in the same lab in Cambridge as James Watson and Francis Crick when they published the structure of DNA, was the guest speaker. His view was that it was an extraordinarily exciting time to be in science, and that to really understand human biology we needed a human protein structure project.

So the initial idea was to establish the molecular shape, the three dimensional structure, of every protein in the body. This was a big ask, especially considering at that point we didn’t know how many protein-coding genes there were in the human genome, although the working estimate at the time was 100,000. (We still don’t really know the answer to this, but it looks to be between 20-40,000.)  And if that wasn’t a big enough problem, it didn’t take into account how difficult it can be to solve a protein structure. Years can be lost in the lab trying to produce protein that is suitable to work with.

Around 1997 various pilot projects started, notably in Japan. Along the line the aim of the project grew and grew. Why limit ourselves to one genome when there are so many others?

On a practical level this makes sense. You can spend years struggling with a human proten only to find that a virtually identical one from a pig works like magic. Plus, the human genome was practically the beginning for the field of genomics, now 1000s of genomes have been sequenced. And if we’re hoping to use this information to treat disease, then we’ll need to know what the protein structures of micro-organisms look like and, importantly,  what proteins these bacteria have that we haven’t so that we can make drugs that disable only bacterial ones and not our own.

To solve all the structures of every genome is a Herculean task, partly because of the sheer scale of the task and partly because it is never-ending because we are discovering new organisms and thus new genomes.

In practice, the idea is to solve enough structures, which means thousands of structures, to know what’s out there.  In an ideal world, we’d reach a point that for each new genome that is sequenced, we could say:  ‘Ah, that new gene is very similar to one we’ve seen before in budding yeast, so we can confidently predict that the protein structure will look like this…’

P. Michael Conn “Sourcebook of Models for Biomedical Research”
Humana Press | 2007-12-11 | ISBN:1588299333 | 920 pages | PDF | 14,8 Mb

BOOK DESCRIPTION

The collection of systems represented in the Sourcebook of Models for Biomedical Research reflect the diversity and utility of models that are used in biomedicine. That utility is based on the consideration that observations made in particular organisms will provide insight into the workings of other, more complex systems. Some models have the advantage that the reproductive, mitotic, development or aging cycles are rapid compared with those in humans; others are utilized because individual proteins may be studied in an advantageous way and have human homologs. Other organisms are facile to grow in laboratory settings, lend themselves to convenient analyses, have defined genomes or present especially good human models of human or animal disease. The Sourcebook of Models for Biomedical Research is a comprehensive and extensive collection of these important medical parallels. While the entire book is not devoted to the remarkable success of the genomic programs, this work is well represented and indexed within these pages. This volume will be an invaluable resource for pharmaceutical and academic researchers across a wide range of biological fields.

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It’s the Phenome and Not the Genome: Put Your Money on Mortal Flesh

by Abraham Verghese

Strong is your hold O mortal flesh . . .

From The Last Invocation, Walt Whitman

Is it just me, or are you also getting a bit tired of all the hype about the genome? Don’t get me wrong– it’s pretty incredible that in my lifetime we have mapped out the 25,000 plus genes in our DNA. What’s even more amazing is that the price for that chart of the human genome has gone from millions to less than $50,000 and now it takes only a few weeks. I bet by next year it might be a few hundred dollars and take a day! Companies like 23andMe (an innovative venture with a great marketing plan) offer to check you for genetic markers that predict your risk for certain diseases for just a few hundred dollars.

But the fact remains that for most of us, the genotype is much less relevant than the phenotype. What is phenotype? It is the things we can see, the outward or observable physical or biochemical characteristics and they are determined by both your genetic makeup and environmental influences. Your blond hair, your weight, your strange nose, green eyes and that funky shaped little toe of yours –all examples of phenotype.

So what do I mean when I say phenotype is more relevant than genotype? Well, let’s say a new patient, a male, walks into my office and he is in his fifties. Let’s say he happens to have the outline of a pack of cigarettes showing in his front pocket. As a male he already has one risk factor for coronary artery disease–just being male, alas. The cigarettes tell me that he is four times more likely to have a heart attack than his peers who don’t smoke. His risk of sudden death is at least doubled. Let’s say I notice he happens to be carrying more than 30 pounds of extra poundage above the belt line: that allows me to predict he has a higher chance of being at risk for diabetes, if he is not already frankly diabetic. Let’s say that I notice too the pale outline of a recently-removed wedding ring (I can’t help it, my eyes are always looking at the body as text–even when I am out of the hospital), then I know that his risk of death as a  recently divorced man can be double that of his married peers.

At this point, before he has even said a word or before I have examined him, I already know so much about his risk of death and disease. Once we talk and I learn more about his job, his stress, his heredity, his habits, his past illnesses, then my predictions get more accurate. Once he disrobes and I examine him, I might find other phenotypic markers that predict risk (such as yellow plaques related to high cholesterol on his eyelids or elbows; high blood pressure; skin tags and velvety darkened areas of skin that predict diabetes; narrowed blood vessels when I look into the back of his eye . . . the list could go on for pages). In short, I’ll have an excellent sense of my patient’s risk for death or disease. At that point, mapping his whole genome, sexy as it might seem, won’t tell me much more than I know and will probably matter much less than getting him to quit smoking, exercise and lose weight.

The famous Whitehall Study of British Civil Servants ranging in ages from 20 to 64 found that the lower grades of civil service had higher mortality rates from heart disease and from all causes than did people in higher grades, even after accounting for risk factors like obesity and smoking. (Yes, it was counterintuitive and that is why we do studies).  Stress was thought to be the factor responsible for this disparity.

The Whitehall studies are ongoing and one of the latest reports from that study made me think of Walt Whitman and reminded me that the phenotype is so relevant. In their report (titled, “Utility of genetic and non-genetic risk factors in prediction of type 2 diabetes: Whitehall II prospective cohort study” and appearing in the British Medical Journal, 2010 Jan 14;340:b4838), the scientists compared a panel of genetic tests for diabetes (common single nucleotide polymorphisms) with non-genetic or phenotypic findings like age, sex, drug treatment, family history of type 2 diabetes, body mass index, smoking status, HDL, triglycerides, fasting glucose.

What they found was that the phenotypic tests did better. Indeed the gene tests added little to the risk already determined by phenotypes. In their own words, “the addition of genotypes to phenotype based risk models produced only minimal improvement in accuracy of risk estimation  . . .”  Translation: use your eyes, take a good history, weight the patient and get a few simple blood tests, and you can predict risk far better than a panel of genetic tests. 

I am not a Luddite (I find I say that a lot) and indeed, I do think the genome studies will help us eventually understand more about causes of disease, and perhaps even point to particular treatments. But utill then the message for us in the trenches is: Strong is your hold O mortal flesh and that’s where the money (speaking diagnostically) is.

Horizontal and vertical: The evolution of evolution – life – 26 January 2010 – New Scientist
UST suppose that Darwin’s ideas were only a part of the story of evolution. Suppose that a process he never wrote about, and never even imagined, has been controlling the evolution of life throughout most of the Earth’s history. It may sound preposterous, but this is exactly what microbiologist Carl Woese and physicist Nigel Goldenfeld, both at the University of Illinois at Urbana-Champaign, believe. Darwin’s explanation of evolution, they argue, even in its sophisticated modern form, applies only to a recent phase of life on Earth.

At the root of this idea is overwhelming recent evidence for horizontal gene transfer – in which organisms acquire genetic material “horizontally” from other organisms around them, rather than vertically from their parents or ancestors. The donor organisms may not even be the same species. This mechanism is already known to play a huge role in the evolution of microbial genomes, but its consequences have hardly been explored. According to Woese and Goldenfeld, they are profound, and horizontal gene transfer alters the evolutionary process itself. Since micro-organisms represented most of life on Earth for most of the time that life has existed – billions of years, in fact – the most ancient and prevalent form of evolution probably wasn’t Darwinian at all, Woese and Goldenfeld say.

Strong claims, but others are taking them seriously. “Their arguments make sense and their conclusion is very important,” says biologist Jan Sapp of York University in Toronto, Canada. “The process of evolution just isn’t what most evolutionary biologists think it is.”

Vertical hegemony

How could modern biology have gone so badly off track? According to Woese, it is a simple tale of scientific complacency. Evolutionary biology took its modern form in the early 20th century with the establishment of the genetic basis of inheritance: Mendel’s genetics combined with Darwin’s theory of evolution by natural selection. Biologists refer to this as the “modern synthesis”, and it has been the basis for all subsequent developments in molecular biology and genetics. Woese believes that along the way biologists were seduced by their own success into thinking they had found the final truth about all evolution. “Biology built up a facade of mathematics around the juxtaposition of Mendelian genetics with Darwinism,” he says. “And as a result it neglected to study the most important problem in science – the nature of the evolutionary process.”

In particular, he argues, nothing in the modern synthesis explains the most fundamental steps in early life: how evolution could have produced the genetic code and the basic genetic machinery used by all organisms, especially the enzymes and structures involved in translating genetic information into proteins. Most biologists, following Francis Crick, simply supposed that these were uninformative “accidents of history”. That was a big mistake, says Woese, who has made his academic reputation proving the point.

In 1977, Woese stunned biologists when his analysis of the genetic machinery involved in gene expression revealed an entirely new limb of the tree of life. Biologists knew of two major domains: eukaryotes – organisms with cell nuclei, such as animals and plants – and bacteria, which lack cell nuclei. Woese documented a third major domain, the Archaea. These are microbes too, but as distinct from bacteria genetically as both Archaea and bacteria are from eukaryotes. “This was a enormous discovery,” says biologist Norman Pace of the University of Colorado in Boulder. Woese himself sees it as a first step in getting evolutionary biology back on track. Coming to terms with horizontal gene transfer is the next big step.

In the past few years, a host of genome studies have demonstrated that DNA flows readily between the chromosomes of microbes and the external world. Typically around 10 per cent of the genes in many bacterial genomes seem to have been acquired from other organisms in this way, though the proportion can be several times that (New Scientist, 24 January 2009, p 34). So an individual microbe may have access to the genes found in the entire microbial population around it, including those of other microbe species. “It’s natural to wonder if the very concept of an organism in isolation is still valid at this level,” says Goldenfeld.

READ MORE HERE….

Horizontal and vertical: The evolution of evolution – life – 26 January 2010 – New Scientist

The hottest bit of research in breeding today centers on the use of DNA as a tool in evaluating horses and in planning matings. Earlier this month, I wrote about the company created by Emmeline Hill and parters called Equinome. It has already launched a product claiming to decipher genetic information about muscle development that determines whether a racer would be a sprinter, miler, or stayer.

The press release for this new business brought sufficient excitement to the bloodstock ‘net that Hill is the subject of an interview in the new issue of The Thoroughbred Times by John Sparkman. He also has a new post on the subject.

Such is the interest in the research on DNA that bloodstock researcher and technology innovator Les Brinsfield brought an article to my attention from New Zealand. There a group of researchers from China and New Zealand led by Allan Davie are working to find the genetic markers in mitochondrial DNA that would explain the Thoroughbred’s outstanding aerobic capacity for utilizing oxygen.

If they could find differences in mtDNA between racehorses who had high aerobic function and those with lower aerobic function, then they could develop tests to select those horses with high aerobic function before they raced or even if they were unraced.

The researchers are trying to find these markers as a preliminary to a commercial venture because the efficient use of oxygen is the “physiological foundation for elite racing performance in both humans and horses.”

We all want to know which horses are going to be the fastest, and this research could be one way to do that, if the teams from China and New Zealand are successful.

The twist to all the products and plans is that they haven’t actually proven anything in concrete terms. None of them have been used to produce successful racehorses who then have greater predictability for producing more good athletes.

Will that sort of progressive improvement ever result from DNA research? Well, it might. But given what we currently understand about genetic information and its recombination, chance and the vast statistical probabilities of the many different factors that all work in accord suggest that day could be a long way off.

“A Silicon Valley start-up is making the bold claim that it can help eradicate that disease and more than 100 others by alerting parents-to-be who have the carrier genes.” This test is now available for about $700 per couple, a sign that genetic evaluation is coming to the masses.

A productive week of international collaborations leading to new drugs or targets…

Genetic Map of Yeast: A large-scale, genome-wide interaction map of yeast genes was constructed in an international study.  The extensive network of genetic interactions lays out a functional map of the cell where similar biological processes can be grouped together. Yeast has been studied in the past and present because their molecular signaling is similar to human cells and is easy to manipulate.  The detailed “genetic atlas” in this project, a first for any organism, provides important information to better understand genetic functions in relation to diseases.  Their technique also allowed the scientists to map interactions between genes and chemicals, which will aid in choosing drug targets by predicting the extent of the interaction with other genes and how it may affect the cell.  The multi-national project was led by University of Toronto researchers Drs. Brenda Andrews and Charles Boone.  Details of the yeast map study appear in the prestigious journal, Science.

Mutations in Lymphomas: The identity of new mutations associated with specific types of lymphomas is described in this latest Nature Genetics article.  Sequencing of genes involved in the NF-kappaB signalling pathway led to the identification of recurrent mutations affecting the EZH2 histone methyltransferase enzyme.  The oncogene is the second member of this enzyme group found to be mutated in different types of cancer.  Mutations were found in over 21% of a lymphoma subtype, affecting amino acid Tyrosine 641 that renders the enzyme with lower activity.  Dr. Marco Marra at the Michael Smith Genome Sciences Centre (BC Cancer Agency) conducted the sequencing project.

Stopping Alzheimer’s Disease: Inhibition of ACAT1, an enzyme directly involved in cholesterol metabolism, significantly decreases the accumulation of amyloid plaques when tested in a mouse model of Alzheimer.  To gain deeper knowledge of how this works, researchers deleted the ACAT1 gene in mice predisposed to develop Alzheimer’s disease.  The brains of these mice had fewer amyloid plaques with improved cognitive function.  The key finding is that without ACAT1 function, cholesterol accumulates in a subcellular compartment of the cell where it is converted and no longer available to be involved in amyloid plaque formation.  These data supports the use of ACAT1 inhibitors in the battle against Alzheimer’s disease and lends insight into future improvement.  Dr. Nabil Seidah at the Institut de Recherches Cliniques de Montréal collaborated with researchers in the U.S. and published the study in the Proceedings of the National Academy of Sciences.

New Treatment to Stop Malaria: Two enzymes important to the survival of Plasmodium falciparum, the parasite causing malaria, have been discovered in an international collaboration aimed at stopping the drug-resistant parasite.  Malaria parasites invade red blood cells and digest the proteins for fuel to grow and divide until they burst out of the red blood cell and repeat the process again.  The discovery of the parasitic enzymes, PfA-M1 and PfA-M17, which are keys to the digestive process in red blood cells, was the first step in designing therapeutic drugs.  Building three-dimensional structures of the enzymes was the next step in determining how best to target and inhibit the enzyme.  The study suggests that blocking PfA-M1 and Pfa-M17 would prevent the parasite from feasting on the red blood cell and represents a new wave of promising anti-malarial drugs.  McGill University’s Dr. John Dalton led the international research project and is reported in this week’s The Proceedings of the National Academy of Sciences.

Vitamin D fights Crohn’s Disease: Vitamin D deficiency in individuals may contribute to the development of Crohn’s disease, as suggested in this new research report.  Mismanagement of intestinal bacteria triggers an inflammatory response that develops into the autoimmune disorder.  The action of Vitamin D, as the study suggests, is to directly promote the expression of NOD2, which signals to the body of a microbial invasion.  NOD2 then activates NF-kappaB to induce expression of DEFB2 (defensin beta2), an anti-microbial peptide.  To further support Vitamin D’s role, both DEFB2 and NOD2 have been linked to Crohn’s disease in earlier studies.  This is significant to the management of the disease because Vitamin D deficiency is easy to test for through a simple blood test and Vitamin D supplements (and sunlight!) are readily available.  Dr. John White and his team at McGill University and the Université de Montréal published their study in the Journal of Biological Chemistry.

As we approach the topics of DNA and genetics,I would like to suggest a book that would allow our classroom discussions to penetrate even further into the ever so exciting human genome. Written by Matt Ridley, Genome: The Autobiography of a Species in 23 Chapters, offers an in-depth but simplistic look at each of the 23 pairs of chromosomes that make up every Homo sapien.

You will uncover how an Ape’s 24 pairs of chromosomes gave rise to our 23 pair, when two fused together, resulting in our being ninety-eight percent genetically identical. You will follow history as the race to discover the structure of DNA ensued. Each chromosome will be presented in its entirety as it should work, as well as what happens when there is a slight mutation. For example, on chromosome 4 an extra three letters, CAG, will result in Huntington’s disease, an extremely debilitating and fatal disease.

All in all this is a fantastic book with an immense amount of scientific and interesting information. These next couple of months are going to be filled with mind-boggling information about what makes you different from the person next to you. Reading this book will only make it better!

“There are twenty-three chapters, called CHROMOSOMES.

Each chapter contains several thousand stories, called GENES.

Each story is made up of paragraphs, called EXONS, which are interrupted by advertisements called INTRONS.

Each paragraph is made up of words, called CODONS.

Each word is written in letters called BASES.”¹

¹Ridley, Matt. Genome: The Autobiography of a Species in 23 Chapters. Great Britain: Fourth Estate, 1999. pg. 7

Television is just corporate and government propaganda.

**

**

It may be possible to reintegrate television and other centralized (that is non-internet) media into a non-propagandistic model.  One could see it as a study in cultural detritus, little floating fragments of meaning quite separate from the “forms”—shows, commercials, lead-ins etc.  Detached from their original contexts and sources, these bits would have almost no weight or substance at all, or only in a vague sense.  Then an entire nomenclature of these free floating particles of sense could be devised.  Isn’t this what marketing research analysts have been at work on for decades now? 

**

**

Only by first changing the culture, by deepening and calming it, can we hope to change the medium that still dominates it.  Of course, in a quieter, more intelligent culture, there is every reason to believe that television would not adapt—it would simply vanish through lack of interest.

**

**

The internet, which relies on the principle of maximum participation, requiring the active engagement of many users to function, is far superior to television or radio.  And if the aspect of intertextuality were developed to its fullest extent, it might someday surpass mere printed text, too.  Of course there is an intertextual element to print as well, but it has remained untouched and unused for centuries.

**

**

The seemingly endless discussion amongst the monastics on the inner reflections and counter-reflections of the aspect of the soul—like mirrors shining light off each other so as to keep intensifying it—was the last time the true capacity of the written word was hinted at.  This went on throughout the Middle Ages, with the sonorous voices of the monks echoing to each other, and was succeeded by the individual and its lone voice calling out for its own aggrandizement, beating its breast in the wilderness of self-referentiality.  How pathetic.

**

**

We are all existentialists, no matter what.

**

**

Upon closer inspection, the texts of the monks yield innumerable errors made through restatement and reinterpretation, a situation that we should not seek to correct by untangling the coils, but rather by adding more material to the original, and then snipping off useful bits to employ as separate fragments.  The same method works well with classical authors.

**

**

One can hope that the discovery of the human genome, a single complex object of study around which many minds can record their thoughts and onto which many hands can accrete further data-streams, might yield something similar in scope to the accomplishment of the monks.  Too many scientific discoveries give birth to a form of commentary that begins in a common place, but then goes off in divergent directions, never to re-converge.  This results in some new discoveries, but it also makes one wonder how many more have been missed.  There is far less internal reciprocity to science than most people imagine.

**

** 

Lucretius was an atomist, and a brilliant theorist, but in his own time he was rejected and his fellow Epicureans were labeled heretics and degenerates by “good, decent” Romans.  Look at what a short distance we’ve come since then.  We should give up, the suicide whispers, and we are strongly tempted.

**

**

Austerity, detachment, equanimity of spirit—all are expressed here:

                                                  nam quodcumque suis mutatum finibus exit

                                                  continuo hoc mors est illius quod fuit ante.*

Wonderful. 

**

**

The idea of the persistence of substance is the essence of essentialism, so to speak.  One needn’t fear the words “essence” or “substance” so long as they are not accompanied by this meaning.  The real threat from “essence” today is its reconstitution through the corporation.  It has come around to meet us from the opposite direction. 

**

**

We are not only existentialists, we are better existentialists than we realize.

**

**

Death matures us.  We graduate to adulthood through loss.

______________

* for whatever in changing leaves the bounds of its own nature/this is immediately the death of what was before (De Rerum Natura).

Marine invertebrates are some of the most bizarre and beautiful animals on the planet, and thrive in the toughest parts of the oceans.
Divers swim into a shoal of predatory Humboldt squid as they emerge from the ocean depths to hunt in packs. When cuttlefish gather to mate, their bodies flash in stroboscopic colours. Time-lapse photography reveals thousands of starfish gathering under the Arctic ice to devour a seal carcass.
A giant octopus commits suicide for her young. A camera follows her into a cave which she walls up, then she protects her eggs until she starves.
The greatest living structures on earth, coral reefs, are created by tiny animals in some of the world’s most inhospitable waters.
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A few months ago, I wrote about a press release:

Using the Google Phone’s built-in bar code reader, Dr. Pellionisz demonstrated how personal genome computing can detect genome-friendly and genome-supportive products from foods to cosmetics to building materials and beyond.

You upload data from personal health record system such as Microsoft Healthvault or Google Health; genomic data from 23andMe or Navigenics to your smartphone and then by using the bar code reader, you can find products that are probably good for you based on your genomic and health profiles. Though the system has several limitations (e.g. how useful genomic data is right now regarding medical decisions), it sounds quite interesting.

Here is the process on video:

Humans were once an endangered species

Humans were once an endangered species

January 21, 2010 by Lin Edwards <!–

–>

Enlarge

Temporal and Geographical Distribution of Hominid Populations Redrawn from Stringer (2003). From: Genetic Analysis of Lice Supports Direct Contact between Modern and Archaic Humans Reed DL, Smith VS, Hammond SL, Rogers AR, Clayton DH PLoS Biology Vol. 2, No. 11, e340 doi:10.1371/journal.pbio.0020340. Image via Wikipedia.

(PhysOrg.com) — Scientists from the University of Utah in Salt Lake City in the U.S. have calculated that 1.2 million years ago, at a time when our ancestors were spreading through Africa, Europe and Asia, there were probably only around 18,500 individuals capable of breeding (and no more than 26,000). This made them an endangered species with a smaller population than today’s species such as gorillas (approximately 25,000 breeding individuals) and chimpanzees (an estimated 21,000). They remained an endangered species for around one million years.

Modern humans are known to have less genetic variation than other living primates, even though our current population is many orders of magnitude greater. Researchers studying specific genetic lineages have proposed a number of explanations for this, such as recent “bottlenecks”, which are events in which a significant proportion of the population is killed or prevented from reproducing. One such event was the Toba super-volcano in Indonesia that erupted around 70,000 years ago, triggering a nuclear winter. Only an estimated 15,000 humans are thought to have survived. Another explanation is that the numbers of humans and our ancestors were chronically low throughout the last two million years, sometimes with only 10,000 breeding individuals surviving.

The new research is concerned with the entire genome rather than specific genetic lineages studied in the earlier research work. Using a new method of studying genetic markers of DNA in the genome has allowed geneticists to study the genetics not only modern humans, but also our early ancestors such as Homo erectus (thought the most likely to be our direct ancestors), H. ergaster and archaic H. sapiens. Remarkably, they found there was enough information in only two human DNA sequences to estimate the ancient population size.

Human geneticist Lynn B. Jorde and colleagues studied parts of the genome containing mobile elements called Alu sequences, which are sections of DNA around 300 base-pairs long that randomly insert themselves into the genome. This is a rare occurrence, but once inserted, they tend to stay in place over generations, and act as markers, rather like fossils, for ancient parts of the genome. On average, regions containing Alu insertions are older than other regions, and because they are old these regions have been shaped more by the forces that applied to ancient populations than to recent bottlenecks (such as Toba) and expansions.

The researchers studied mutations in the DNA near these Alu markers in two modern human genomes that have been completely sequenced. Older regions containing Alu sequences have more mutations because they have been in existence longer, and the researchers used the nucleotide diversity to estimate the age of the region of the genome. They then compared these regions with the overall diversity in the two genomes to estimate the differences in effective population size, and thus the genetic diversity between modern humans and our ancestors.

From these studies, they calculated there was more genetic diversity in our early ancestors than there is in modern humans. They also came to the conclusion that there had been a catastrophic event around one million years ago that was at least as devastating as the Toba volcanic eruption, and which had almost wiped out the species.

Jorde said that humans and our ancestors have gone through cycles of large population size and also periods when we were endangered. Professor Jorde and his team’s findings were reported online in PNAS, the Proceedings of the National Academy of Sciences on January 19.

More information: Mobile elements reveal small population size in the ancient ancestors of Homo sapiens, PNAS, DOI:10.1073/pnas.0909000107

© 2010 PhysOrg.com

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In 2003 researchers mapped out the first human genome. It led to an explosion of knowledge about why people are different from one another. That meant for the first time doctors could learn more about why one person gets cancer or responds to treatment when another doesn’t. Researchers at Mayo Clinic have mapped out the genome of a woman with multiple myeloma. And the information from her has prompted them to change the way they treat patients with this deadly cancer.

National Geographic Adventure Mag: Genographic, Spencer Wells

	WALKING THROUGH TIME: Spencer Wells, accompanied by a party of Bushmen, treks across a dry watering hole in northern Namibia.

Spencer Wells knows exactly where he wants to go next: the Tibesti mountains. He wants to fly to Libya, now that it’s open to Westerners again, then hail a camel caravan across the Libyan desert to Chad, where the seven inactive volcanoes of the Tibesti rise 11,000 feet (3,353 meters) from the central Sahara: a private world of crags and chasms seldom seen by more than a handful of outsiders. Like any intrepid traveler, he’s unfazed by the prospect of deadly North African windstorms and burning desert heat. The land mines near the border of Libya and Chad do pose a problem, but local guides can thread a path. As for the fierce and isolated Tubu, who’ve ruled the Tibesti long enough for Herodotus to have named them the Troglodytes, they’re the real payoff. Wells wants to learn their oral history, how their ancestors exacted tribute from traders passing to and from the Middle East, and what this crossroads reveals about one of Earth’s earliest cultures on the continent where all human life began. Then he wants to stick a cheek swab into each of their mouths to collect a generous gob of DNA-rich saliva.

Wells, 36, is a population geneticist using science in global pursuit of the greatest story not yet told: the story of how humankind traveled from its origins in Africa to populate the planet. The most telling clues lie with isolated, indigenous tribes like the Tubu, for their DNA remains, in a sense, the purest. Their unique genetic markers, characteristic mutations in a defined sequence of DNA, are like flags waving from the place their ancestors have inhabited for thousands of years—the starting point for ancient migrations. Any venturesome Tubu who crossed the Sahara to see the outlying world, and propagated in the process, passed on one or another of those genetic markers to his or her offspring. Any traveler who came through the Tibesti and intermarried did the same. Wells might take a cheek swab from an investment banker in Boston and find that same genetic marker: proof that one of those Tubu created a family line that leads, in some circuitous way, over continents and generations, from the Tibesti to an oak-paneled office in Back Bay. It’s in the hope of tracing myriad journeys such as this that Wells, a newly named National Geographic Explorer-in-Residence, is undertaking one of the most ambitious and expensive research adventures in the National Geographic Society’s 117-year history: the grandly named Genographic Project.

At a cost of 40 million dollars over five years, the brunt of it borne by National Geographic, IBM, and the Waitt Family Foundation, the Genographic Project under Wells’s direction is establishing 11 DNA-sampling centers around the world, with the goal of collecting 100,000 cheek swabs or blood samples from mostly indigenous peoples like the Tubu. A sense of urgency infuses the project: Year by year, at an ever quickening rate, the outside world is crowding in on, and at the same time absorbing, indigenous peoples. A Tubu who moves to Paris will still have the genetic markers that distinguish him as a Tubu, but the geographical context for his markers will be gone. As for the Tubu who remain in the Tibesti mountains, they may marry more with outsiders as modern technology makes contact more likely. Generation by generation, tracing the last routes of historical migration of such isolated people grows that much harder. Wells wants to map as many routes as he can while their geographical origins are relatively intact.

Wells has a nifty and novel idea to help fund and publicize the project. “We’re taking this directly to the people,” he declares. “Because in addition to doing this work with indigenous populations, we’re going to be offering for sale to the public, in the developed world mostly, the opportunity to do this cheek-swab test to see how they fit into the family tree.” For about a hundred dollars, a contributor gets his or her very own cheek-swab kit along with a map of migratory routes, as Wells has charted them thus far, that is like an explorer’s parchment map of the New World. “Because these participation kits are totally anonymous, there’s no way anyone can find out anything about your history except you,” Wells says. “Once the results are ready, you can access the Web site (www.nationalgeographic.com/genographic) for extensive details about genetics, archaeology, history, and the context for genetic variation. Your sample, if you choose, can be put into our database, so that it adds to this increasing data set about genetic variation all over the world. But when you purchase your cheek-swab kit, you’re also funding research, and part of the money will be channeled back to taking samples from the 100,000 people.”

For a man just weeks from the public announcement of this global gambit, Wells is forgivably a bit tense on an early spring day in his fourth-floor office at National Geographic’s Washington, D.C., headquarters. Ruddy and fit—a whole lot more fit than your typical laboratory-bound scientist—he radiates a steely cool, like a field marshal on the eve of battle. The inevitable layman’s queries about genetics elicit crisp details about mitochondrial DNA and Y chromosomes in gleaming, perfectly formed paragraphs. Most of us talk in analog; Wells is digital. Only a framed picture on the shelf suggests that not all goes according to plan. Wells’s two young daughters are with their mother in Geneva; a divorce is under way. For ten years of fieldwork around the world, Wells is paying a human toll.

To Wells, the Genographic Project is a perfect double helix of history and science, the origins of which trace, for him, to a university science lab in Lubbock, Texas, which became a second home when he was all of nine years old. That was when Wells’s mother, a professor at Texas Tech University’s medical school, took time off to earn a Ph.D. in biology and let her son hang out while she performed her experiments. The same year, 1979, Wells was also strongly influenced by English polymath James Burke’s ten-part television series Connections, with its anecdotal braiding of science and history. After earning a B.S. in biology at 19, Phi Beta Kappa, from the University of Texas at Austin, Wells took his own Ph.D. at Harvard University in evolutionary genetics—the historical side of the science, as he says—and studied fruit flies with world-renowned population geneticist Richard Lewontin.

Fruit flies had served as an ideal test case since the early 20th century, when Thomas Hunt Morgan used them in his Fly Room at Columbia University to show how chromosomes worked, to prove that chromosomes were made up of genes, and to show how genes were passed down. But at the end of the day, Wells says, “I’m not that interested in fruit fly history. But I am interested in human population history. I wanted to apply some of those methods to human history.”

“What I appreciate about Spencer is that he is not the kind of scientist who is only interested in his favorite molecule or DNA mutation,” says fellow geneticist and Genographic Project coordinator Lluis Quintana-Murci of the Pasteur Institute in Paris. “Many scientists tend to be closed off in their little rooms. He always had much broader interests—human biology and history. And he uses genetics as a tool to unravel the past.”

For that, Wells went to Stanford University to work with the “grand old man” of human population genetics, Luca Cavalli-Sforza, who is now a chairman of the Genographic Advisory Board. He wanted to learn what the bold new field of genome sequencing—identifying every gene in a living thing and mapping its relation to every other gene—could do for tracing human history.

For years, scientists had studied blood for genealogical clues. Blood characteristics suggested the different cultures of a family tree. But blood was little help for telling when a Middle Eastern people, say, might have migrated to western Europe and intermarried. What the scientists needed, Wells says, was a clock.

That clock came in the form of DNA. The seemingly endless ribbons of DNA found in human hair, saliva, blood—any cell in the body—are made up of three billion individual units, known as A, C, G, and T. Subtle variations in that sequence are what genetically distinguish one person from another. As incredibly able as the human system is at replicating each unique sequence from one generation to the next, a small number of variations, or mutations, do occasionally crop up. By analyzing specific regions of the DNA, comparing the results to known reference sequences, and identifying differences that are anthropologically significant, geneticists are able to track mutations.

“They’re like spelling mistakes,” Wells says. “Imagine you’re copying a very long document, and occasionally you’ll put an A where there should be a C. And that mistake has been translated down through the generations, and more mistakes have accumulated. So the longer the lineage has been in existence, the more mistakes the sequence is going to have. And if you know the rate at which those mistakes occur, you can actually estimate how long this individual has been evolving since that origin, how long his DNA has been accumulating changes.”

Initially Cavalli-Sforza’s team focused on something called mitochondrial DNA—a good choice because it appears frequently in the cell, so it’s easy to find and track. “It’s effectively the remnant of a bacteria that became engulfed by the cell about a billion years ago,” Wells explains. “And all higher organisms have these structures in their cells.” As Cavalli-Sforza’s group knew, mitochondrial DNA is inherited strictly maternally. A mother passes it to her son, but the son can’t pass it on. Only from mother to daughter does it keep descending, generation to generation. In most African tribes, women did the traveling, mostly to find mates, while the men stayed put. So the story that mitochondrial DNA told was only half of the story. Cavalli-Sforza’s geneticists needed a piece of male DNA they could study to prove their theory of African origins and migration. That was when the team’s researchers began studying variations in the Y chromosome, which is passed down from fathers to sons and had, up until then, been a maddeningly inscrutable bit of DNA.

By studying how mutations had accumulated in both mitochondrial DNA and Y chromosomes and determining the rate at which those mutations occur—like counting tree rings—the geneticists made a dramatic conclusion: The populations with the greatest number of mutations were in sub-Saharan Africa. They had the oldest living lineages, which meant they were, beyond the shadow of a genealogical doubt, directly related to the earliest of our traceable ancestors. Their DNA marked the spot where humankind began.

Archaeology had suggested this, of course. But what the geneticists saw from their DNA sequencing of current-day Africans is that their ancestors appeared to have lived as the only humans on Earth as recently as 60,000 years ago. That was when they started migrating, taking their genetic mutations with them, and passing them down. Why did they leave when they did? Because 10,000 years before that, one of the Pleistocene epoch’s worst cold snaps nearly drove humankind to extinction, and these were the survivors, whose better brains made them more adaptable.

If Steven Spielberg were making the movie, a fur-garbed posse of these plucky migrants—the first adventure travelers!—would set off together at dawn across the savanna, covering miles each day in search of fresh prey. In fact, the “Great Leap Forward,” as anthropologist Jared Diamond puts it (in a facetious borrow from Mao Zedong), probably occurred less than 10,000 years ago. The intellectual leap, Diamond and Wells contend, came first: A few children born with higher intelligence and better communication skills, capable of fashioning better tools, passed their superior genes to offspring who came to dominate their clans.

Smarter humans learned to hunt certain species. As those species migrated a few miles every year or so, or died out on the clan’s home turf, the hunters pursued them. Drought accelerated these trends by causing animals to disperse more widely. Eventually, a few migrants reached the Indian Ocean and adopted a fishing life. Little by little, they migrated north up Africa’s east coast. Some traversed the Red Sea—perhaps on simple log rafts. Others headed farther north to the Mediterranean. By 45,000 years ago, as garbage dumps from the time attest, hunters with relatively sophisticated tools were ensconced on the Mediterranean’s shores, engaged in art and other shows of complex culture, and curious about the unknown lands that lay before them in every direction.

Wells wanted DNA samples to fill in this tantalizingly sketchy picture of humankind’s origins. Where had the first of those migrating Africans gone? What routes had they taken, in just tens of thousands of years, to populate the rest of the world?

For the complete profile on population geneticist Spencer Wells and the Genographic Project, pick up the August 2005 issue of Adventure.

The Genographic Project – Human Migration, Population Genetics, Maps, DNA – National Geographic

A Landmark Study of the Human Journey

Where do you really come from? And how did you get to where you live today? DNA studies suggest that all humans today descend from a group of African ancestors who—about 60,000 years ago—began a remarkable journey.

The Genographic Project is seeking to chart new knowledge about the migratory history of the human species by using sophisticated laboratory and computer analysis of DNA contributed by hundreds of thousands of people from around the world. In this unprecedented and of real-time research effort, the Genographic Project is closing the gaps of what science knows today about humankind’s ancient migration stories.

The Genographic Project is a five-year research partnership led by National Geographic Explorer-in-Residence Dr. Spencer Wells. Dr. Wells and a team of renowned international scientists and IBM researchers, are using cutting-edge genetic and computational technologies to analyze historical patterns in DNA from participants around the world to better understand our human genetic roots. The three components of the project are: to gather field research data in collaboration with indigenous and traditional peoples around the world; to invite the general public to join the project by purchasing a Genographic Project Public Participation Kit; and to use proceeds from Genographic Public Participation Kit sales to further field research and the Genographic Legacy Fund which in turn supports indigenous conservation and revitalization projects. The Project is anonymous, non-medical, non-profit and all results will be placed in the public domain following scientific peer publication.

Mammals’ ability to learn new tricks is the key to survival in the knife-edge world of hunters and hunted. In a TV first, a killer whale off the Falklands does something unique: it sneaks into a pool where elephant seal pups learn to swim and snatches them, saving itself the trouble of hunting in the open sea. Slow-motion cameras reveal the star-nosed mole’s newly-discovered technique for smelling prey underwater: it exhales then inhales a bubble of air ten times per second. Young ibex soon learn the only way to escape a fox – run up an almost vertical cliff face – and young stoats fight mock battles, learning the skills that make them one of the world’s most efficient predators.
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Gliobastoma (astrocytoma) WHO grade IV - MRI coronal view, post contrast. 15 year old boy;Image via Wikipedia

Another Article on Glioblastoma Multiforme that I’ve written on scientificblogging.com!

The most common form of  brain tumor in adults, glioblastoma multiforme (GBM), is not in fact a single disease but appears to be four distinct molecular subtypes, according to a study by The Cancer Genome Atlas (TCGA) Research Network. The researchers in this study also found that response to aggressive chemotherapy and radiation differed by subtype.The research team for TCGA is a collaborative effort funded by the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI), both parts of the National Institutes of Health. The Cancer Genome Atlas (TCGA) aims to catalogue and discover major cancer-causing genome alterations in large cohorts of human tumours through integrated multi-dimensional analyses.(3)The study, published Jan. 19, 2010 in Cancer Cell, provides a solid framework for investigation of targeted therapies that may improve the near uniformly fatal prognosis of this cancer.Although the findings do not affect current clinical practice, the researchers said the results may lead to more personalized approaches to treating groups of GBM patients based on their genomic alterations.Rest of article can be read by following the link below.

http://www.scientificblogging.com/biochem_geek/blog/cancer_genome_atlas_identifies_distinct_subtypes_brain_cancer_glioblastoma_multiforme

Posted by: Audiegrl

Aurochs were immortalized in prehistoric cave paintings and admired for their brute strength and “elephantine” size by Julius Caesar

Aurochs are depicted in ochre and charcoal in paintings found on the walls of cave galleries such as those at Lascaux in France Photo: ALAMY

The huge cattle with sweeping horns which once roamed the forests of Europe have not been seen for nearly 400 years.

Now Italian scientists are hoping to use genetic expertise and selective breeding of modern-day wild cattle to recreate the fearsome beasts which weighed around 2,200lb and stood 6.5 feet at the shoulder.

Breeds of large cattle which most closely resemble Bos primigenius, such as Highland cattle and the white Maremma breed from Italy, are being bred with each other in a technique known as “back-breeding“.

At the same time, scientists say they have for the first time created a map of the auroch’s genome, so that they know precisely what type of animal they are trying to replicate.

“We were able to analyse auroch DNA from preserved bone material and create a rough map of its genome that should allow us to breed animals nearly identical to aurochs,” said team leader Donato Matassino, head of the Consortium for Experimental Biotechnology in Benevento, in the southern Campania region.

“We’ve already made our first round of crosses between three breeds native to Britain, Spain and Italy. Now we just have to wait and see how the calves turn out.”

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The Register reports -

According to the boffins’ analysis, most parts of the human and chimp (Pan troglodytes) genome are very similar, differing by “less than one per cent” in gene number. But the human male’s Y chromosome is hugely more complex than that of our remote arboreal cousins.

Continue reading.

The male sex chromosome, long dismissed as the underachieving runt of the genome, has now been fully sequenced in a common chimpanzee. And comparison with its human counterpart — the only other Y chromosome to have been sequenced in such detail — reveals a rate of change that puts the rest of the genome to shame.

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David Attenborough looks at the extraordinary ends to which animals and plants go in order to survive. Featuring epic spectacles, amazing TV firsts and examples of new wildlife behaviour.

There are 200 million insects for each of us. They are the most successful animal group ever. Their key is an armoured covering that takes on almost any shape. Darwin’s stag beetle fights in the tree tops with huge curved jaws. The camera flies with millions of monarch butterflies which migrate 2000 miles, navigating by the sun. Super-slow motion shows a bombardier beetle firing boiling liquid at enemies through a rotating nozzle. A honey bee army stings a raiding bear into submission. Grass cutter ants march like a Roman army, harvesting grass they cannot actually eat. They cultivate a fungus that breaks the grass down for them. Their giant colony is the closest thing in nature to the complexity of a human city.
Awesome & beautiful!!!!
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The estimated cost of the Human Genome Project that aimed to sequence the human genome was around $350 million. The dream line is around $1000, and now here is a new milestone. Illumina HiSeq 2000 costs $650,000, but it can sequence a genome for $10,000 and generates 200 gigabytes per run. Though even if we cross the $1000 line somewhere in the near future, I don’t think we are ready to implement this huge amont of data into medical decision making effectively. Technology moves faster than our understanding of clinical genomics.

Fellow bloggers’ reports:

• GenomeWeb
• Pathogens
• Genetic Future
• Genomics Law Report
• PolITiGenomics

The race for the $1000 genome is serious. Do you remember the new genome sequencer of Helicos? 1 billion basepairs a day: