Researchers at the University of California, Davis, have just reported a small but significant accomplishment: catching the replication of a single DNA molecule on video for the first time. And the footage has revealed some surprising details about this structure on which all life depends.

DNA is composed of two strands bound together in a helical shape, like a twisting ladder. These strands are made of four basesadenine, guanine, cytosine and thymine, abbreviated as A, G, C and T, respectivelystrung together in various patterns and paired in specific ways across the rungs of the ladders. A always pairs with T, and C always pairs with G. Sugar and phosphate molecules help provide architectural support to the ladder-like structure. Human DNA contains about 3 billion bases. Discrete, repeated sequences of bases form the individual genes that encode the instructions for all our working parts. And every time a cell divides, which happens incredibly often, DNA replicates so that each new cell contains a complete copy of our entire genome, or genetic blueprint.

A digital representation of the human genome. Scientists at UC Davis have discovered that DNA replication is not as smooth as they thought. Mario Tama/Getty Images

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The process of DNA replication isa tremendous source of wonder and focus forresearch. The helix must unwind and have each strand copied smoothly and quickly. An enzyme called helicase triggers the unwinding and another called primase initiates the replication process. Athird, called polymerase, travels the length of a strand, adding the requisite base pairs along the way, leaving behind a new strand. Imagine splitting a ladder down the middle and assembling matching halves so that where there was once one ladder now there are two. That is DNA replication, only in place of saws, nails, wood and glue, there are enzymes and many microscopic and complex processes. Mysteries aboundwhen it comes to thishereditary material.

To better probe those mysteries, geneticist and microbiologist Stephen Kowalcyzkowski and colleagues watched DNA from bacteria replicate. They wanted to see exactly how fast the enzymes worked on each strand.

This first-ever view, shown in the video above, revealed a surprise: replication stopped unpredictably and moved at a varying pace. "The speed can vary about 10-fold," Kowalczykowski said in a statement. The two strands also replicated at different speeds.Sometimes the copying stalled on one strand while proceeding on the other. "We've shown that there is no coordination between the strands," said Kowalczykowski. "They are completely autonomous." The process, the researchers report in their study, published in Cell, is much more random than previously suspected.

The three enzymeshelicase, primase and polymeraseare also not alwys in sync. Even if polymerase stops its replication work, helicase can keep unzipping the helix. That lack of coordination leaves the half-helix of DNA exposed and vulnerable to damage. Such exposure is known to trigger repair mechanisms within the cell. Errors in replicating DNA, while often corrected, can also result ingenetic abnormalities that in turn lead to diseases.

This new look at DNA transforms the scientific understanding about replication. "It's a real paradigm shift," saidKowalcyzkowski, "and undermines a great deal of what's in the textbooks."

Continued here:
DNA Replication Filmed for First Time Shows How Awkward and Random Genetics Is - Newsweek

June 20, 2017 by Silke Schmidt Megan McClean and Cameron Stewart have built a novel optogenetic system that monitors light-controlled yeast gene expression. This optostat regulates cellular processes, similar to how a thermostat controls room temperature. Credit: Stephanie Precourt

A user-friendly switch for controlling room temperature, the thermostat is a classic example of the kind of tools engineers build.

For biological systems research, Megan McClean and Cameron Stewart have taken the idea of a thermostat several steps furtherand using their invention, which combines the power of light, computers and genetics, researchers can now build an "optostat" that is remarkably similar to the thermostat in our homes.

"All you need is three ingredients," says McClean, an assistant professor of biomedical engineering at the University of Wisconsin-Madison. "An organism that grows well in cell culture, the ability to insert a light-sensitive switch into its genome, and a computer-controlled microscope that images what you want the organism to produce."

The optostat is a fully automated system that connects these three ingredients with electronics and freely available software. Using the light-responsive part of a plant protein to control the expression of a single gene in baker's yeast, the researchers were able to record images of the fluorescent protein produced by that gene continuously for up to 10 days, capturing how the cells responded to the amount of light they received. While light controlled the expression of the gene of interest, it did not affect the transcription of thousands of other yeast genes.

The system contains everything the cells need to grow in excess, except for one limiting nutrient that is provided through controlled release. Like a thermostat, the optostat can automatically adjust the amount of light needed to obtain a desired protein concentration.

Stewart and McClean recently described their optogenetic system in the Journal of Visualized Experiments, allowing other researchersespecially biologists without an engineering backgroundto set it up in their own labs.

Stewart compares their invention to a car's cruise control system. "Cars, throttles, and speedometers already existed, but cruise control combined them with a feedback system," he explains. "In our case, growing cells in a 'chemostat' to maintain a constant growth rate has been possible since the 1950s. But our novel contribution is to connect this chemostat to a light bulb to administer inputs, and to a microscope to measure outputs."

The new optostat is the only system of its kind that can sample and monitor the same cell culture continuously over a long period of time. This allows researchers to study any biological pathway of interest by tuning a single parameter and keeping everything else, including the cells' growth rate, the same.

Optogeneticsthe use of light-sensitive proteins as regulators of a variety of cellular processeshas been a growing research field for the last ten years, McClean says. Since the response of plants to light has been studied extensively, plant-derived proteins make ideal optogenetic tools.

One application of optogenetic systems that McClean is particularly interested in involves Candida albicans, the most common of more than 20 species of yeast-like fungi that live in our intestinal tract. They are usually harmless, but their overgrowth can trigger infections in certain body parts, such as the mouth or throat (thrust) and the vagina (yeast infection). When the fungus enters the bloodstream and spreads through the body, it may cause dangerous invasive infections.

Some Candida species have recently caused severe illness in hospitalized patients and are now considered a global health threat. "Our drug arsenal for fungi is very limited because these organisms are so similar to our own cells," McClean says. "That makes their emerging resistance to antifungal drugs especially disconcerting."

Candida species are a threat to hospitalized patients because they tend to form a thin mat, or biofilm, on hip or knee implants and intravenous catheters. By controlling different regulators of C. albicans growth with a light-sensitive switch, McClean hopes to learn what makes the organism change from its stable form in a biofilmlong and skinnyto its less stable, round form that may pop off the biofilm and disperse into the bloodstream. In the future, that knowledge may help inhibit fungal infections in humans without causing toxic side effects.

"One of the unique aspects of fungal biology is its potential to disperse into the bloodstream," McClean says. "In order to study the factors that cause it, we need a controllable system that allows time for a biofilm to form and then make light-induced perturbations. With several modifications we plan to implement next, we believe our optogenetic system will eventually provide that kind of tool."

Explore further: All yeasts are not created equal

Yeast. Great if you want to make bread or wine. Not so hot if it turns up as Candida albicans in large quantities in your body and makes you sick.

Light can be used as an accurate method to control gene expression, shows groundbreaking optogenetics study by University of Colorado, Duke University and University of Helsinki researchers.

Researchers at the University of Alberta have developed a new method of controlling biology at the cellular level using light.

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A team of researchers at Cincinnati Children's Hospital Medical Center has developed an antibody that could prevent Candida infections that often afflict hospitalized patients who receive central lines.

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A user-friendly switch for controlling room temperature, the thermostat is a classic example of the kind of tools engineers build.

Chimpanzees adapt their behaviour to match the group, just as humans do, according to new research led by the University of St Andrews.

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Building a biological control switch with light, genetics, and engineering ingenuity - Phys.Org

Ron (Rupert Grint), Hermione (Emma Watson), Harry (Daniel Radcliffe) and Ginny (Bonnie Wright) gather at platform 9 and 3/4 to send the next generation of witches and wizards to Hogwarts, in "The Deathly Hallows: Part 2" (Warner Bros. Pictures, 2011).

WASHINGTON In the world of "Harry Potter," magical ability runs in the family. Witches and wizards have parents who are witches or wizards, and they are typically born into families that have already produced generations of wand-wielders.

There are exceptions to this rule Hermione Granger was born to a pair of Muggles (people without magical powers), and Harry's roommate, Seamus Finnigan, was the son of a Muggle father and an Irish witch.

And sometimes, a witch and wizard couple will produce a non-magical person known as a squib such as the cranky Hogwarts caretaker Argus Filch, or Harry's Privet Drive neighbor and childhood babysitter, Arabella Figg. Magic appears to follow some of the same rules as other traits that are inherited, but what could be the genetic factors that explain why someone is born a witch or a wizard or without any magical ability at all? [Science Fact or Fiction: The Plausibility of 10 Sci-Fi Concepts]

A roomful of people here at Future Con got a crash course in wizarding DNA and the basic workings of genetics on June 17, at a talk hosted by Eric Spana, an assistant professor in the Department of Biology at Duke University, in North Carolina.

Genetics can explain more in the "Potterverse" than just magical ability like the Weasley family's signature hair color, for example. Red hair is caused by a mutation in the MC1R gene; but it's a recessive trait, which means it crops up only when the mutation is present in both sets of DNA that a child inherits. Arthur and Molly Weasley are both redheads, thereby ensuring that their offspring would inherit two copies of the gene mutation, and would be born with red hair, Spana explained.

However, in the very last scene of the final movie, "The Deathly Hallows: Part 2" (Warner Bros. 2011), we see that Harry and Ginny's young daughter Lily has red hair, even though Harry's hair is brown. In that case, the gene mutation came from Harry's copy of his mother's DNA. His mother had red hair, so he inherited the mutation but it couldn't do anything until it encountered a second copy of the mutated gene in Ginny Weasley's DNA, Spana said.

Eric Spana, an assistant professor in the Department of Biology at Duke University, describes wizard DNA at the Future Con panel, "Harry Potter and the Genetics of Wizarding."

Is the wizarding gene recessive, like the gene for red hair? Hagrid, the half-giant-half-wizard groundskeeper at Hogwarts, proves that it isn't, according to Spana. Giants have no magical ability, and Hagrid was born to a giant mother and a wizard father. For him to be born a wizard with only one copy of the wizard gene in his DNA, magical ability would have to be a dominant trait, Spana said.

This example seems to hint that magic is linked to the Y chromosome, which means the gene would have to come from the father's DNA (females have two X chromosomes, while males have one X and one Y chromosome). However, Seamus Finnigan had a Muggle father and a witch mother, which suggests it can't be the Y chromosome that carries the gene. That would make wizarding ability something called an autosome a trait that isn't linked to sex characteristics, Spana said. [Unraveling the Human Genome: 6 Molecular Milestones]

"It's an autosomal, dominant trait," he concluded.

But if it's a dominant trait, then where did Hermione's magic come from, as the first witch to be born in her family? Hermione is an example of a "de novo" mutation a genetic mutation that appears in a lineage for the first time, due to a mutation in the egg or sperm, or within the embryo itself following fertilization. And this type of mutation occurs quite frequently in real life, Spana said.

A random mutation could also explain how a non-magical squib could be born to two magical parents, he added.

If the wizarding gene is working correctly, it makes a certain type of protein. The phenotype, or observable characteristics resulting from that activity, is magical ability. But if there's a mutation in that gene Spana suggested calling it the "SQUIB" mutation a different type of protein turns the magic gene off. If one parent's DNA carries a copy of the SQUIB mutation, it can turn off the wizarding protein, which cancels a child's ability to do magic.

"We do this in fruit flies all the time," Spana said, referring to manipulation of hereditable traits in general and not of genes for magic.

And then there are individual variations in wizarding ability, with some witches and wizards recognized to be more powerful than their fellows. Could genetics explain that as well? Not entirely, Spana said.

"I come from the 'basketball school' genetics makes you 6-foot-8, but it doesn't give you skill. Working at it gives you skill," Spana said. Hermione's power, as well as the varying degrees of expertise demonstrated by the Weasley children, suggests that one's magical ability is not completely reliant on genetics, he said.

As the discussion drew to a close, an audience member asked Spana the one question that must accompany any serious conversation about the Potterverse: Which Hogwarts house would the Sorting Hat have placed him into?

"I'm 100 percent Slytherin or as I like to call it, 'Management,'" Spana said.

Original article on Live Science.

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Genetics of Wizardry: Were Harry Potter's Magical Powers Written in His DNA? - Live Science

Roche Holdings(NASDAQOTH:RHHBY)surprisinglycut ties with NewLink Genetics (NASDAQ:NLNK)on GDC-0919 last week, and that decision puts NewLink Genetics further back behindIncyte Corporationin theraceto develop a new class of cancer-fighting drugs called IDO inhibitors.

Roche Holdings' decision is particularly disappointing because industry watchers had thought GDC-0919 would be NewLink Genetics most competitive IDO-ihibitor. Now that GDC-0919's future is in flux,investors are right to wonder what's up next for NewLink Genetics.

Indoleamine 2,3-dioxygenase (IDO) is a protein that has immunosuppressive effects, and because cancer cells can hijack it to evade detection by the immune system, drug developers think inhibiting its activity could help other cancer medications work better.

IMAGE SOURCE: GETTY IMAGES.

At the forefront of this research are NewLink Genetics and Incyte. Until now, NewLink Genetics has been developing indoximod and GDC-0919, while Incyte Corporation has been developing epacadostat.

In April,NewLink Genetics reported that the objective response rate in a 60-person phase 2 study evaluating indoximod alongside Merck & Co.'s (NYSE:MRK) Keytruda in advanced melanoma was 52%. If you include patients with stable disease, the rate increases to 72%.

Similarly, Incyte Corporation reported data from its own melanoma trial earlier this year showing patient's objective response rate to epacadostat plus Keytruda was 58%. A total of 74% had a complete response, partial response, or stable disease.

In both cases, the findings suggest each of these drugs could win FDA approval someday. Especially since theFDA approved Keytruda for use as a monotherapy in advanced melanoma patients after it delivered a 33% objective response rate.

However, it's Incyte's drug that's closer to FDA review, and that first-mover advantage, plus the similarity in results from these trials,could make it difficult for indoximod to win away market share.

Because of Incyte's lead over indoximod, industry watchers' had hoped trials evaluating GDC-0919 wouldshow it works better than epacadostat in cancers other than melanoma.Unfortunately, that doesn't appear to be the case. Last week, Roche presented data onGDC-0919 at the American Society of Clinical Oncology (ASCO) conference that was lackluster, and it appears those results were a big reason why Roche has decided to walk away from developing it any further.

Specifically, adding GDC-0919 to Roche's Tecentriq (a drug that works similarly to Keytruda) resulted in anobjective response rate of just 9% across a variety of cancers. For comparison, adding epacadostat to Keytruda resulted in objective response rates of between 30% to 35% in a variety of cancers, including non-small cell lung cancer.

NewLink Genetics hasn't licensed indoximod to anyone yet, and now that it's getting the rights to GDC-0919 back, it's got a decision to make. Developing both of these drugs concurrently would be costly, and the company probably can't afford it.

As of March 31, it has $118 million in cash on its books, but it's burning through that cash at a rate of $12 million per quarter. Cash burn is likely to increase from here given plans to start a registration ready trial of indoximod in melanoma this year. Currently, management expects it will finish 2017 with $75 million in cash, and that suggests to me that a cash crunch could be coming in 2018.

Ideally, NewLink Genetics probably wants to convince another company to share in development costs by out-licensing GDC-0919 again. However, that seems less likely given Roche's data at ASCO.

It's also possible thatNewLink Genetics would consider selling itself lock, stock, and barrel. However, finding a buyer could be unlikely too. The most logical suitors would be companies marketing PD-1 checkpoint inhibitors that they could pair up with NewLink Genetics drugs, but the two leaders in this class areBristol-Myers Squibb and Merck & Co., and they're already working with Incyte.

If licensing and M&A is off the table, then NewLink Genetics next option could be tapping equity investors for more money. However,that's not going to be easy given its crumbling share price.

NLNK data by YCharts

In the end, NewLink Genetics might have to focus on indoximod trials and hold-off on developing GDC-0919 -- at least until new data emerges that reignites its share price.

Potentially, trials evaluatingindoximod plus Abraxane and gemcitabine in pancreatic cancer could make that happen. Data from aphase 1/2 trial evaluating indoximod alongside these treatments are expected soon. Fortunately, the bar for success is set pretty low. The ojective response rate for Abraxane plus gemcitabine alone is only 23% in trials, and an interim look at adding indoximod to these drugs produced an objective response rate of 45%.

Having said that, investors might want to keep their optimism in check. Pancreatic cancer is notoriously hard to treat, and there's no guarantee that interim trial results will be confirmed.

Overall,the risks facing NewLink Genetics are big, and the stakes for its survival are higher now than they were before Roche's decision. Therefore, investors should approach this company with a big dose of caution, at least until we know for sure if indoximod's pancreatic cancer trial is a success.

Todd Campbell has no position in any stocks mentioned. His clients may have positions in the companies mentioned. The Motley Fool has no position in any of the stocks mentioned. The Motley Fool has a disclosure policy.

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A Surprising Disappointment Derails NewLink Genetics -- What's ... - Motley Fool

Seattle Genetics Inc. SGEN, +0.61% said Monday that it is discontinuing the Phase 3 clinical trial of its acute myeloid leukemia treatment, SGN-CD33A, after data indicated a higher rate of deaths, including fatal infections. The company said it will suspend patient enrollment and treatment, and will closely review the data and consult with the Food and Drug Administration to determine future plans. "This is a disappointing and unexpected result for the CASCADE trial. Patient safety is our highest priority, and we will closely review the data and evaluate next steps," said Chief Executive Clay Siegall. The stock, which is still inactive in premarket trade, has rallied 22% year to date through Friday, while the iShares Nasdaq Biotechnology ETF IBB, +2.10% has climbed 10% and the S&P 500 SPX, -0.52% has gained 8.7%.

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Seattle Genetics suspends trial of leukemia treatment after data showed higher rate of death - MarketWatch

More than half of American adults drink coffee daily. But how does that caffeine affect us, biologically? It depends on genetics.

Is morning just not morning without a steaming mug of coffee in your hand? Youre not alone, as a little more than half of American adults drink coffee daily, for the taste, the aroma, the pick-me-up or all of the above. I suspect that numbers even higher in Seattle. As an added bonus, moderate coffee consumption is linked to a number of health benefits, including reduced risk of developing type 2 diabetes. But for some people, the caffeine in even moderate amounts of coffee could have a downside.

The safe caffeine limit for healthy nonpregnant adults is 400 milligrams (mg) per day, the amount in four average 8-ounce cups of brewed coffee. The average caffeine intake in this country is about 180 mg per day, but those averages are just that average. Some people get less caffeine than that, and others get more, sometimes much more, because not all coffee is average.

For example, a 12-ounce medium roast at Starbucks has about 235 mg. Get a refill and youve exceeded your limit. Then theres the growing trend of super-high-octane coffee, with brands like Black Insomnia and Death Wish competing for the title of worlds strongest coffee and clocking in at about 700 mg of caffeine for a 12-ounce cup. While thats not optimal for anyone, for some people it might be risky the collision of genetic differences in how we metabolize caffeine with the latest generation of high-caffeine beverages may have unintended consequences.

How caffeine makes you feel is partly due to your tolerance level, but its largely due to genetics. Of greatest concern is one gene CYP1A2 that alters how caffeine affects us, but in ways we dont actually feel. Depending on which version of the CYP1A2 gene you inherited, you metabolize (break down) caffeine slow or fast. Lets look at why that matters.

For a long time, drinking more than a few cups of coffee was linked to an increased risk of heart attack. But when researchers looked closer several years ago, they found that risk was only increased among people who were slow caffeine metabolizers. For slow metabolizers, one cup per day wasnt a problem, but after that, the risk started to rise. Slow metabolizers under the age of 50 who drink four cups per day or more had quadruple the risk of having a heart attack. By contrast, fast metabolizers especially those under age 59 actually saw reduced risk of heart attack with a moderate one to three cups per day.

Four cups of coffee for one person might be the biological equivalent of one cup for someone else, just depending on how much of that caffeine sticks around in their system, said Ahmed El-Sohemy, PhD, one of the studys authors, at the 2017 Nutrition & Health conference in Phoenix in May. He said more recent studies have found similar effects for risk of pre-diabetes, hypertension and kidney disease in slow metabolizers.

El-Sohemy said that slow metabolizers dont self-regulate caffeine because they dont feel the difference. So what does this mean for you? You could get tested for the CYP1A2 gene, but insurance might not cover it. Or, you could play it safe and enjoy a moderately sized cup or two and leave it at that. You could go decaf or half-caf decaffeinated coffee contains the same health-promoting compounds, including phytonutrients, found in regular coffee. Finally, if you find you rely on coffee to get through the day, maybe its time to cultivate a more beneficial source of energy sleep!

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Is coffee your friend or foe? Genetics makes a difference - Seattle Times

Seattle Genetics said it is discontinuing a Phase 3 clinical trial after data showed a higher rate of deaths, including fatal infections in acute myeloid leukemia patients receiving its drug than in the studys other patients.

By Seattle Times business staff

Seattle Genetics said it is discontinuing a Phase 3 clinical trial after data showed a higher rate of deaths, including fatal infections in acute myeloid leukemia (AML) patients receiving its drug than in the studys other patients.

As a result of data it received June 16, the company said Monday, Seattle Genetics is suspending patient enrollment and treatment in all of its clinical trials on the drug, called vadastuximab talirine or SGN-CD33A. The drug was also being used in a Phase 1/2 clinical trial in myelodysplastic syndrome (MDS).

Both studies were testing the drug as a so-called front-line treatment, meaning it would be an early therapy rather than a second or third choice for patients who dont respond to initial treatment. It is pursuing similar studies in various cancers for its leading approved drug, Adcetris.

The Bothell-based company did not disclose the number of patient deaths or other details in its statement early Monday. It said it will review the data and consult with the federal Food and Drug Administration (FDA) to determine future plans for the drugs development program.

Three early-stage studies SGN-CD33A in AML patients receiving stem-cell transplants were placed on a clinical hold by the FDA in December, after what the company reported were four fatal events, but the hold was lifted in March. The study discontinued Monday was already in progress at that time.

Seattle Genetics said in December that more than 300 patients had been treated with SGN-CD33A in various clinical trials.

The Phase 3 trial discontinued Monday was a double-blind study of SGN-CD33A in combination with either of two hypomethylating agents, compared with those agents alone, in older patients with newly diagnosed AML.

Seattle Genetics has spent more than $100 million over the past five years on developing the drug, making it the companys second most expensive development program after Adcetris, it said in a regulatory filing last month.

This is a disappointing and unexpected result, said Clay Siegall, president and chief executive officer at Seattle Genetics. Patient safety is our highest priority, and we will closely review the data and evaluate next steps. AML is a devastating disease with a poor prognosis in most patients, and there is a great need for therapeutics against this disease.

Shares of Seattle Genetics opened the day down 8 percent but recovered somewhat, closing at $61.88, down $2.64 or 4.1 percent.

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Seattle Genetics ends clinical trial of leukemia drug after 'a higher rate of deaths' - The Seattle Times

Writing in The Hindu, Tony Joseph has claimed that genetics has very sure-footedly resolved the debate about whether there was a migration of Indo-European people (Aryans) into the subcontinent around 2000-1500 BCE apparently, the unambiguous answer is yes. To anyone with a nodding acquaintance with the literature in the area, such an assertion is unfounded. Given the sheer importance of this topic to Indian history, it is necessary to challenge Josephs one-sided presentation of facts. There also seems to be much that is questionable in his very approach, and this deserves scrutiny.

Conclusions decided upon in advance?

Ironically, after saying that the dominant narrative so far that genetics had disproved Aryan immigration had not been nuanced, he abandons nuance himself.

Noting the clear slant in his article, and his quoting of Razib Khan, who was sacked as a columnist by the New York Times apparently for racist views, I got in touch with Dr Gyaneshwer Chaubey, senior scientist at the Estonian Biocentre, Tartu, and a widely-published scholar in the area. Indeed, Chaubey is a co-author with Peter Underhill (whom Joseph quotes) of the 2015 study on the R1a haplogroup that Joseph cites in his article.

To my surprise, it turned out that that Joseph had contacted Chaubey and sought his opinion for his article. Chaubey further told me he was shocked by the drift of the article that appeared eventually, and was extremely disappointed at the spin Joseph had placed on his work, and that his opinions seemed to have been selectively omitted by Joseph a fact he let Joseph know immediately after the article was published, but to no avail.

Having known Chaubeys views for some time now especially that the origin of the R1a is far from settled I was not surprised to hear this. This in itself gives the lie to Josephs claims of the unambiguous conclusions of genetics about the hypothetical Aryan immigration.

Mitochondrial DNA vs Y-chromosomal DNA

Joseph claims that we only had mitochondrial (mt-) DNA (which is inherited from the mother) analysis till recently, which failed to capture the fact that it may have been mostly Aryan males who migrated first to the subcontinent and intermarried with the native women. This, apparently, has been conclusively established by a recent avalanche of Y-chromosomal DNA (which is inherited exclusively by sons from their fathers) data, which shows a Bronze Age gene flow into the subcontinent. This remark seems to suggest an embarrassing lack of familiarity with the literature.

Also, does Joseph seriously imagine geneticists would not have envisaged the possibility of males spearheading a migration all along? The first suggestion that Y-chromosomal DNA analysis may be making a case for Indo-European immigration, and the proposal that the R1a haplogroup (M17) may be a marker for this migration, was made as early as 2001.

This was subsequently contradicted in 2006 in a seminal Y-chromosomal DNA study by a group that included Richard Villems, Toomas Kivisild and Mait Metspalu, also of the Estonian Biocentre, and among the leading authorities in this area (Kivisild has since moved to Cambridge, but Villems and Metspalu are Chaubeys current colleagues at Tartu). Villems and Kivisild were, in fact, co-authors in the 2001 paper I just mentioned, but revised their view about a migration after a fresh analysis of more extensive data.

This paper, concluded, It is not necessary, based on the current evidence, to look beyond South Asia for the origins of the paternal heritage of the majority of Indians at the time of the onset of settled agriculture. The perennial concept of people, language, and agriculture arriving to India together through the northwest corridor does not hold up to close scrutiny. Recent claims for a linkage of haplogroups J2, L, R1a, and R2 with a contemporaneous origin for the majority of the Indian castes paternal lineages from outside the subcontinent are rejected...

The dominant narrative that Joseph talks about actually stems from this study, and Im not sure he is qualified to dismiss it as a bit of a stretch. This study, which has never really been contradicted, is, in fact, published in a much more respected journal than BMC Evolutionary Biology from where Joseph cites Martin Richards paper. This is significant, as good studies in this area have generally found a place in highly-ranked journals, even if they have arrived at diverging conclusions.

Indeed, this itself would suggest there are very eminent geneticists who do not regard it as settled that the R1a may have entered the subcontinent from outside. Chaubey himself is one such, and is not very pleased that Joseph has not accurately presented the divergent views of scholars on the question, choosing, instead to present it as done and dusted.

The R1a haplogroup

There are some inherent issues in regarding the R1a as a marker for any hypothetical Indo-European migration.

Firstly, Iranian populations, who are also speakers of the Indo-Iranian family of languages like most North Indians, have very little R1a. Also, tribal groups like the Chenchus of Andhra Pradesh and the Saharias of Madhya Pradesh show anomalously high proportions of R1a. The Chenchus speak a Dravidian language, and the Saharias an Austro-Asiatic one (though they have recently adopted Indo-European languages).

They are hunter-gatherer peoples who remained stunningly isolated without admixing much with other population groups, and consequently, their lifestyles have remained startlingly unchanged for millennia, as they would have been before the start of settled agriculture.

The best that studies which argued that the R1a could be used as a marker for the hypothetical Indo-European migration could do was to simply ignore these groups as aberrations. But is that very convincing? Note that it is possible no, almost certainly the case there were many tribal communities with high proportions of R1a that, unlike the Chenchus and Saharias, were assimilated into the caste matrix over the millennia. So how correct is it to link the R1a with an Indo-European migration?

Significantly, Richards et al acknowledge Chaubeys critical advice with their manuscript. That seems like a euphemism for saying that Chaubey (and, by extension, the Tartu school) had reservations about their conclusions, which is probably why he is not a co-author. So what should one make of Josephs claim that geneticists have converged on an answer?

If Underhill expressly stated to Joseph that he has now reversed his published position that there has been no significant genetic influx to Asia from Europe, indeed specifically that he is now convinced the R1a entered the subcontinent from outside, Joseph bafflingly does not reproduce this statement in his article.

The statement Joseph actually quotes merely points out that we have better data now, but that is not the same thing. Joseph also cites his 2015 paper, in which Chaubey is a co-author, but this paper actually underscores the limits of current technology, and says their data is too preliminary to jump to conclusions about migrations and culture shifts.

The genetic data at present resolution shows that the R1a branch present in India is a cousin clade of branches present in Europe, Central Asia, Middle East and the Caucasus; it had a common ancestry with these regions which is more than 6000 years old, but to argue that the Indian R1a branch has resulted from a migration from Central Asia, it should be derived from the Central Asian branch, which is not the case, as Chaubey pointed out.

In other words, contrary to what Joseph claims, as the Y-chromosomal DNA data stands today, there is no support for a recent migration into the subcontinent.

Ancestral North Indians (ANI) and Ancestral South Indians (ASI)

Joseph continues to tilt at windmills when talking about the ANI / ASI construct of David Reich et al., who used analysis autosomal DNA, which is different from mt- and Y-chromosomal DNA.

Joseph writes, ...this theoretical structure was stretched beyond reason and was used to argue that these two groups came to India tens of thousands of years ago, long before the migration of Indo-European language speakers that is supposed to have happened only about 4,000 to 3,500 years ago.

One doesnt know what to make of this. It was geneticists including Lalji Singh and K Thangaraj who were Reichs co-authors in the paper which proposed the ANI/ASI construct who argued that the ANI and ASI are considerably more than 12,500 years old, and not the result of any recent migration.

He then goes on to quote David Reich arguing in favour of a migration from the Steppe around 2500 BCE. Once again, Joseph presents this view as the last word on the subject, although not all geneticists agree.

For instance, Partha Majumdar and co-workers have very recently come up with quite different conclusions in the journal, Human Genetics: In contrast to the more ancient ancestry in the South than in the North that has been claimed, we detected very similar coalescence times within Northern and Southern non-tribal Indian populations. A closest neighbour analysis in the phylogeny showed that Indian populations have an affinity towards Southern European populations and that the time of divergence from these populations substantially predated the Indo-European migration into India, probably reflecting ancient shared ancestry rather than the Indo-European migration, which had little effect on Indian male lineages (emphasis mine).

The Evidence From Archaeology

Since Joseph believed he was shocking those who believed genetic analysis had disproved Aryan immigration theories, I shall return the favour.

Hypotheses of migrations of Bronze Age populations into the subcontinent fall afoul of archaeological evidence. Paradoxically, as I have described earlier, bronze itself goes missing from the archaeological record for several centuries that are supposed to correspond to the settling of the Bronze Age Indo-Europeans into the subcontinent. As one of the foremost authorities in the archaeology of the Indus Valley Civilisation, Professor Jonathan Mark Kenoyer of the University of Wisconsin points out, this actually reflects a prolonged lack of contact of the subcontinent with the regions the Aryans are supposed to have entered from.

Also, geological evidence shows that the Ghaggar-Hakra river, along whose channels numerous Harappan sites have been discovered, was the River Saraswati described in the Vedas and other ancient literature; indeed, the team of geologists led by Peter D Clift which carried out the geological studies asserted that the descriptions of the Saraswati in those texts was remarkably accurate, as I wrote in an earlier article.

Such findings negate the Aryan immigration model, establish the overlap (if not identity) of the Indus Valley and Vedic cultures, and push back the dates for the composition of the Vedic and other literature considerably.

Agriculture In Subcontinent Indigenous, Autochthonous

There is clear evidence of continuous inhabitation of the Gangetic plain from the Pleistocene. It is also abundantly clear that agriculture was developed indigenously, autochthonously, based on exploiting local resources, at multiple centres on the subcontinent the Saraswati-Indus region, the Gangetic plain, Eastern, Central and Peninsular India in a natural progression from a hunting-gathering lifestyle to a sedentary one, with no external stimulus, but with strong interaction between various regions of the subcontinent themselves right from the earliest Neolithic.

The myth that the founding of agriculture, whether in the Indus Valley or elsewhere in the subcontinent, is owed to migrations from West Asia (the so-called Fertile Crescent) is not supported by archaeological evidence.

Based on current evidence, whether genetic or archaeological, Josephs conclusion that, ...we are a multi-source civilization, not a single-source one, drawing its cultural impulses, its tradition and practices from a variety of lineages and migration histories, is quite simply totally wrong.

One cannot impressed by Josephs quoting of a blogger with a very questionable history like Razib Khan, while selectively omitting the comments of a known scholar in the area like Dr Gyaneshwer Chaubey after having sought them himself.

Can one be sure he has not interviewed other scholars, but left out their views from his article as they didnt suit his pre-determined agenda or just didnt interview scholars he felt held such views?

Joseph and others like him are welcome to write on any topic they please, and are even free to take sides in line with their prejudices. Indeed, all he has done is to paint a very recent paper in a not particularly highly-ranked journal as the final word in the debate, while coolly ignoring well-regarded studies which arrive at differing conclusions in significantly higher-ranked journals.

All one asks is, when writing on a much-debated topic like this one, they should at least show the intellectual sincerity to mention divergent points of view, and not try to create a false impression for the lay reader that they have been conclusively addressed. That is neither very honest nor commendable.

Read more:
Genetics Might Be Settling The Aryan Migration Debate, But Not How Left-Liberals Believe - Swarajya

NEW YORK (AP) Stocks that moved substantially or traded heavily Monday:

PerkinElmer Inc., up $4.16 to $67.73

The company, which sells testing equipment and scientific instruments, agreed to buy Euroimmun Medical Laboratory Diagnostics of Germany.

EQT Corp., down $5.26 to $53.51

The energy company agreed to buy Rice Energy for $6.7 billion in cash and stock.

Novodaq Technologies Inc., up $5.70 to $11.70

The maker of surgical technology is being acquired by Stryker Corp.

Valeant Pharmaceuticals International Inc., up 81 cents to $13.47

The company said hedge-fund manager John Paulson, its largest shareholder, will join the companys board.

U.S. Steel Corp., up 64 cents to $20.80

The Wall Street Journal reported that President Donald Trump may announce plans to curb steel imports.

Apple Inc., up $4.07 to $146.34

Technology companies posted some of the biggest gains in the market.

Hain Celestial Group Inc., down 67 cents to $33.24

The Wall Street Journal reported that the organic food company, which hasnt released financial results for more than a year, risks being delisted from the Nasdaq.

Seattle Genetics Inc., down $2.64 to $61.88

The biotechnology company discontinued a clinical trial of vadastuximab talirine in older acute myeloid leukemia patients.

Read the original:
Apple, PerkinElmer rise; EQT, Seattle Genetics fall - Seattle Times

Nazneen Rahman at the day job: head of genetics, Institute of Cancer Research and the Royal Marsden Hospital. Photograph: Wellcome

Ive had an exciting and unusual few weeks. My group published a scientific paper revealing a new genetic cause of a childhood kidney cancer called Wilms tumour. This discovery has been of immediate benefit to families, providing an explanation for why their child got cancer, and information about cancer risks for other family members. During the same period, I also released my second album of original songs, called Answers No Questions. On one day, I found myself singing live on Radio London in the morning and talking genetics to the World Service in the evening.

Over the past few weeks, I have found it increasingly difficult to know quite how to answer the ubiquitous question what do you do?

For most of my adult life, I have replied: Im a scientist and a doctor. It is an accurate description. I am professor of human genetics at the Institute of Cancer Research, London, and head of cancer genetics at the Royal Marsden Hospital. For 20 years, my work has focused on identifying gene mutations that predispose us to getting cancer and then using that information to help patients and their families.

But I am also a singer-songwriter. This is a smaller activity than my science, but far more than hobby. I release music that people pay good money to experience.

As my music has become better known, more and more people have asked me about my unusual career combination. Dubiously, admiringly, wistfully, jealously, but most often simply because they are intrigued by the motivations and the practicalities.

This has forced me to consider how, if at all, these parts of my life are related. At first, I was adamant they were distinct facets of my character. I railed against modern societys pervasive need to simplify and pigeon-hole the human spirit. Most people have multiple passions and drivers. I am fascinated by these subterranean pursuits. One of the joys of sharing my previously secret musical existence (its not been all joy but thats another column) is that many scientists now share their secret passions with me pot throwing, flugel playing, novelty cakemaking, fire eating scientists are as wondrously idiosyncratic in their appetites as the rest of society.

I also rail against the cliche that people are drawn to science and music because they both have a mathematical basis. It may be true for some, but it has no relevance to my passion for music. I was singing complex harmonies to pop songs long before I learned the theory of music. I am an intuitive, emotional, spontaneous songwriter with little idea of the key, notes or time I am composing in until I have to write it down. There is little science in my music, but I have come to believe there may be music in my science. There is a kinship in how I do science and how I make music that flouts the division of science and the arts that our education system promotes.

My branch of science is genetics. Genetics is underpinned by a simple four-letter DNA code (designated by A, C, G, T). This code dictates how our bodies work. And how they can fail. This beautiful code is framed, shaped, constrained and enhanced by a multitudinous orchestra of associates that determine when, how, where, how long and how strong different parts of the code are played in each of our 30tn cells. DNA is also extraordinary in being able to copy itself with unbelievable accuracy while retaining the ability to mutate and evolve. The sophisticated controls and balances are breathtaking in their elegance. Our recent childhood cancer gene discovery revealed some insights into these control mechanisms and how cancer can occur if they go wrong. Studying genetics provides an endless variety of patterns to unravel, problems to solve, questions to answer. Gratifyingly, it also provides endless opportunities to bring benefits to humanity. In a hundred lifetimes I would not run out of genetic questions that excite me.

Music is underpinned by a simple 12-letter note code (designated by C, C#, D, D#, E, F, F#, G, G#, A, A#, B). These notes can be layered in almost infinite ways to produce music. In a hundred lifetimes I would not run out of music to write. My challenge has never been about finding the time to write songs, it has always been about finding the time to not lose songs. Snippets of music and lyrics are my constant companions. Most disappear into the clouds like lost balloons. But every now and again, I reach up, grab a string and tie one down, just before it is lost for ever.

Science and music make me feel like Im swimming in infinity pools of possibility, but within structures that keep me from drowning. The potential and expectation to keep delivering new things can be daunting to scientists and artists. The DNA code in genetics and the note code in music are my lifelines. They let me be audacious and unfettered. They give me confidence to dive in, even when I cant see the shore on the other side.

And the practicalities of delivering science and music are quite similar for me. Science is typically funded as three- to five-year projects. For example, I am currently leading a 4m collaborative programme, called the Transforming Genetic Medicine Initiative, which is building the knowledge base, tools and processes needed to deliver genetic medicine. To get science funding, you need to present, in great detail, a persuasive, innovative concept that seems worthwhile and feasible. But once you receive the funding there is considerable creative licence to alter the project, within the overall concept, because science is fast moving. You cannot predict everything you will do at the cutting-edge of knowledge, five years in advance.

My albums have also had three-year lifespans, though I didnt plan it that way. I dont plan them at all. My songs tend to be stories about the complexities of everyday life, inspired by words, subjects or images that briefly, randomly, ensnare me. I dont know what the songs will be about before I write them. There is no overall concept for the albums, at least not consciously. And yet I see now that each album had a central theme that wasnt apparent to me when I was writing them. Cant Clip My Wings, which I released in 2014, includes songs about how we adapt to loss. Lost loves, lost lives, lost dreams. My new album, Answers No Questions, includes songs about choice the complexities, burdens, excitement, pain and joys of making choices.

As I am writing this, I wonder if I am forcing these connections, if they are a post-hoc construct that allows me to give a more pleasing answer to why I am both scientist and songwriter. But I have truly come to believe that, in me, science and music are different manifestations of the same need. A central deep desire to create new things elegant, beautiful, new things. It doesnt much matter if its a scientific discovery, a clinic protocol that makes things easier for patients or a song that tells a human story from a fresh perspective. When it works it feels amazing. Even when it doesnt work, the journey is always paved with nuggets of enlightenment that feed into future creations.

So what do I do?

I think, at my core, I am a creative, though it would be perplexing to many if I started to describe myself this way. Science and music are the mediums in which I happen to create, undoubtedly an unusual combination. But maybe only because we are relentlessly conditioned, from an early age, to believe we must choose whether we are in the science or the arts camp. People from the arts camp routinely tell me they were hopeless at science, sometimes apologetically, sometimes as a badge of honour, a mark of their creativity. Likewise, scientists worry that any proficiency in creativity might be interpreted as a deficiency in objectivity, the bedrock of science. It seems our society has lapsed into considering activity in the sciences and the arts a zero-sum game. It is not.

What would happen if we stopped constraining ourselves and our children in this way? If we embraced and fostered fluid boundaries between the sciences and the arts? If many more people were able to cross freely in and out of both worlds, successfully and unapologetically?

I believe science, art, individuals and society would reap countless benefits.

Answers No Questions is out now; nazneenrahman.com

See more here:
Nazneen Rahman: 'Science and music are mediums in which I create' - The Guardian