Were Neandertals the Original Redheaded Strangers?

Were Neandertals the Original Redheaded Strangers?

Analysis of a pigmentation gene in Neandertals suggests that the extinct hominids had humanlike skin color patterns

	FRECKLED CAVE DWELLERS:  Hot on the tail of a study showing Neandertals may have been able to speak, a new report reveals that some of the extinct hominids may have been redheads.

When you think of Neandertals, freckles probably aren't the first facial features that come to mind.

But, a new analysis of genetic material from the remains of two Neandertals indicates that some members of the ancient hominid population may well have been pale-skinned redheads. An international team of researchers reached that conclusion after studying a segment of the gene MC1R that controls melanin, which is responsible for skin and hair color. 

"In modern humans, this gene is under a strong selective constraint in Africa, but has experienced a relaxation of this constraint in European populations coming out from Africa 40,000 years ago and, therefore, it has accumulated quite a lot of variation on it," says Carles Lalueza-Fox, an associate professor of animal biology at Spain's University of Barcelona and a co-author of the new study appearing in Science. "I thought that Neandertal's ancestors, having experienced something similar, but half a million years ago, would have accumulated lots of variation in this gene also. But, of course, the mutations were going to be at different places of the gene."

The two Neandertal samples the researchers examined were found in separate locations: Monti Lessini, Italy, and El Sidrón Cave in northern Spain. A 128–base pair fragment of MC1R was isolated from the Italian sample. (For reference, there are estimated to be 250,000,000 base pairs in the entire Neandertal genome.) The researchers found a single base substitution that was unique when compared with the same section of DNA from 3,700 people (indicating that it was not contaminated by human DNA); the Spanish Neandertal sample contained the same mutation.

To determine the skin and hair color this mutation would have caused, the scientists created a copy of the human version of gene with the Neandertal substitution in it and then injected it into a culture of pigment cells. They were particularly interested in observing how the MC1R protein expressed by the altered gene interacted with a second protein—α-MSH—which triggers melanin production.

When the two substances mixed, the researchers say, they had a relatively low level of interaction, indicating that low levels of melanin would be produced—a reaction that mirrors the results in genes of humans with red hair and fair complexions. Pale skin allows those living at higher latitudes and exposed to less frequent and weaker sunlight to more efficiently synthesize vitamin D. (This vitamin helps the body absorb calcium to keep bones strong and healthy; deficiencies can lead to bone disorders such as the childhood disease rickets, which softens bones.)

"Chances are that the gene was full of functional variants in the Neandertal populations that provoked quite a high prevalence of red-haired people," Lalueza-Fox says. "But of course, it still depends on if you are heterozygous [(have two different versions of the gene)] or homozygous for these variants [(like Neandertals and modern Europeans)], so I guess that we should expect the whole range of hair color variation [that is] observed in northern modern Europeans."

Lalueza-Fox says he and his team plan to examine other Neandertal genes to learn more about the species, with eye color, behavior, metabolism, immunity and physiology being of particular interest. As for the findings surrounding MC1R, "It was a big opportunity to have an inference of a trait," he says, "that will never be found in the fossil record." 

Fact or Fiction?: Stress Causes Gray Hair

Fact or Fiction?: Stress Causes Gray Hair

Scientists have a hunch that the gray hairs we dread (or welcome) may arrive sooner with stress

	STRESS AGES:  While no clear link has been found, scientists believe that stress can lead to more gray in your hair.

Legend has it that Marie Antoinette's hair turned white the night before she was guillotined. Presumably the stress of impending decapitation caused her locks to lose color within hours. Extremely unlikely, scientists say, but stress may play a role in a more gradual graying process. 

 The first silvery strands usually pop up around age 30 for men and age 35 for women, but graying can begin as early as high school for some and as late as the 50s for others.  

Graying begins inside the sunken pits in the scalp called follicles. A typical human head has about 100,000 of these teardrop-shaped cavities, each capable of sprouting several hairs in a lifetime. At the bottom of each follicle is a hair-growing factory where cells work together to assemble colored hair. Keratinocytes (epidermal cells) build the hair from the bottom up, stacking atop one another and eventually dying, leaving behind mostly keratin, a colorless protein that gives hair its texture and strength. (Keratin is also a primary component of nails, the outer layer of skin, animal hooves and claws?even rhinoceros horns.)  

As keratinocytes construct hairs, neighboring melanocytes manufacture a pigment called melanin, which is delivered to the keratinocytes in little packages called melanosomes.

Hair melanin comes in two shades—eumelanin (dark brown or black) and pheomelanin (yellow or red)—that combine in different proportions to create a vast array of human hair colors. Hair that has lost most of its melanin is gray; hair that has lost all of this pigment is white.  

At any given time, around 80 to 90 percent of the hairs on a person's head are in an active growth phase, which may last anywhere from two to seven years. At the end of this stage, the follicle shrivels, the keratinocytes and melanocytes undergo programmed cell death (apoptosis), and the follicle enters a resting phase, during which the hair falls out.  

To begin building a new hair, the follicle factory must be rebuilt. Fresh keratinocytes and melanocytes are recruited from progenitor cells, also called "stem cells," residing at the bottom of the follicle. For unknown reasons, keratinocyte stem cells have a much greater longevity than the melanocyte stem cells, says David Fisher, professor of pediatrics at Harvard Medical School. "It's the gradual depletion of [melanocyte] stem cells that leads to the loss of pigment," he says.  

Does stress accelerate this demise of the melanocyte population? "It is not so simple," Fisher says, noting that the process of graying is a multivariable equation. Stress hormones may impact the survival and / or activity of melanocytes, but no clear link has been found between stress and gray hair.  

Suspicions—and hypotheses—abound, however. "Graying could be a result of chronic free radical damage," says Ralf Paus, professor of dermatology at the University Hospital Schleswig-Holstein in L・eck, Germany. Stress hormones produced either systemically or locally (by cells in the follicle) could produce inflammation that drives the production of free radicals—unstable molecules that damage cells—and "it is possible that these free radicals could influence melanin production or induce bleaching of melanin," Paus says.  

"There is evidence that local expression of stress hormones mediate the signals instructing melanocytes to deliver melanin to keratinocytes," notes Jennifer Lin, a dermatologist who conducts molecular biology research at the Dana-Farber / Harvard Cancer Center in Boston. "Conceivably, if that signal is disrupted, melanin will not deliver pigment to your hair."  

And general practice physicians have observed accelerated graying among patients under stress, says Tyler Cymet, head of family medicine at Sinai Hospital in Baltimore, who conducted a small retrospective study on hair graying among patients at Sinai. "We've seen that people who are stressed two to three years report that they turn gray sooner," he says. 

Cymet suspects that going gray is "genetically outlined, but stress and lifestyle give you variation of plus or minus five to 10 years." Blonds often appear to go gray later in life because white strands easily hide in a sea of light hair when in fact those who are likely to have the darkest hair (people of African and Asian ancestry) seem to retain their color longer.

In short, scientists are beginning to gather clues that stress can hasten the graying process, but there is no scientific evidence demonstrating a cause-and-effect relationship.  

So what happened to Marie Antoinette? There are at least three possible explanations: She may have suffered from sudden onset of the rare autoimmune disease alopecia areata, which attacks pigmented hairs, causing them to fall out, leaving the white (nonpigmented) strands behind. Or the stress of the situation could have generated a swarm of free radicals in her hair follicles, which traveled along the hair shafts, destroying pigment and creating a bleaching effect. Or maybe she just stopped wearing her wigs—revealing she had gray hair all along. 

Climate Change's Uncertainty Principle

Climate Change's Uncertainty Principle

Scientists say they can never be sure exactly how extreme global warming might become, but that's no excuse for delaying action  

	UNCERTAIN FUTURE:  Because small changes in things like snow cover or greenhouse gas concentrations lead to big climate effects, scientists will never be certain how bad global warming could be.

The Intergovernmental Panel on Climate Change in its first report in 1990 predicted that temperatures would warm by 0.5 degree Fahrenheit (0.3 degree Celsius) per decade if no efforts were made to restrain greenhouse gas emissions. But the panel of scientists and other experts was wrong: By 2001, the group estimated that average temperatures would increase by 2.7 to 8.1 degrees F (1.5 to 4.5 degrees C) in the 21st century, and they raised the lower end to 3.6 degrees F (2 degrees C) this year in their most recent report. In essence, neither this international team of experts nor any other can say with any certainty just how bad global warming may get.

There is a simple explanation for this, says atmospheric physicist Gerard Roe of the University of Washington (U.W.) in Seattle: Earth's climate is extremely sensitive. In other words, small changes in various physical processes that control climate lead to big results. "If nothing else changed by [warming], a doubling of carbon dioxide would ultimately lead to a temperature change of about 1.2 [degrees] C," [(2.1 degrees F)] Roe says. "In fact, because of internal processes within the climate system, such as changing snow cover, clouds and water vapor in the atmosphere, our best estimate is that the actual warming would be two to four times larger than that."

Some of these feedback processes are poorly understood—like how climate change affects clouds—and many are difficult to model, therefore the climate's propensity to amplify any small change makes predicting how much and how fast the climate will change inherently difficult. "Uncertainty and sensitivity are inextricably linked," Roe says. "Some warming is a virtual certainty, but the amount of that warming is much less certain."

 

Roe and his U.W. co-author, atmospheric physicist Marcia Baker, argue in Science that, because of this inherent climate effect, certainty is a near impossibility, no matter what kind of improvements are made in understanding physical processes or the timescale of observations.

"Once the world has warmed 4 degrees C [(7.2 degrees F)] conditions will be so different from anything we can observe today (and still more different from the last ice age) that it is inherently hard to say when the warming will stop," physicists Myles Allen and David Frame of the University of Oxford wrote in an editorial accompanying the article. "If the true climate sensitivity really is as high as 5 degrees C [(9 degrees F)], the only way our descendants will find that out is if they stubbornly hold greenhouse gas concentrations constant for centuries at our target stabilization level."

Therefore, waiting for more scientific certainty before acting is a mistake, Roe says. "People are comfortable with the idea that stock markets, housing prices and the weather are uncertain, and they are used to making decisions on that basis," he notes.

But this also means that targets such as stabilizing atmospheric concentrations of CO₂ at 450 parts per million (nearly double preindustrial levels) to avoid more than a 3.6 degree F (2 degree C) temperature rise are nearly impossible as well. There is no guarantee that such a target would achieve its stated goal. "Policymakers are always going to be faced with uncertainty and so the only sensible way forward to minimize risk is to adopt an adaptive policy," argues climatologist Gavin Schmidt of the NASA Goddard Institute of Space Studies, "which adjusts emissions targets and incentives based on how well, or badly, things are going."

It also means that scientists and other experts are going to have to monitor measures other than just atmospheric concentration of greenhouse gases to catch catastrophic climate change developing. "It is essential that we designate the harbingers of abrupt and significant changes or, perhaps more importantly, the triggers and thresholds that could commit the planet to these changes well before their tell-tale signs appear," says economist and IPCC author Gary Yohe of Wesleyan University in Middletown, Conn. "We cannot accept the adaptive design completely without having confidence in our abilities to determine exactly what to monitor."

The IPCC has taken a crack at that, identifying 26 "key vulnerabilities" in its most recent assessment, ranging from declines in agricultural productivity to the melting of ice sheets and polar ice cover as well as determining how to judge if they are spiraling out of control. Disappearing Arctic ice is already helping to amplify global warming beyond what the IPCC had predicted in the past. "We already know about as much as we are going to about climate system's response to greenhouse gases," Roe says. "We already have the basis for making the decisions we need to make."

 

Mass Extinctions Tied to Past Climate Changes

Mass Extinctions Tied to Past Climate Changes

Fossil and temperature records over the past 520 million years show a correlation between extinctions and climate change

	FOSSIL RECORD:  Analyzing the fossil record and past temperatures shows that a warming world is bad for the number of different plants and animals on Earth.

Roughly 251 million years ago, an estimated 70 percent of land plants and animals died, along with 84 percent of ocean organisms—an event known as the end Permian extinction. The cause is unknown but it is known that this period was also an extremely warm one. A new analysis of the temperature and fossil records over the past 520 million years reveals that the end of the Permian is not alone in this association: global warming is consistently associated with planetwide die-offs.

"There have been three major greenhouse phases in the time period we analyzed and the peaks in temperature of each coincide with mass extinctions," says ecologist Peter Mayhew of the University of York in England, who led the research examining the fossil and temperature records. "The fossil record and temperature data sets already existed but nobody had looked at the relationships between them."

Pairing these data—the relative number of different shallow sea organisms extant during a given time period and the record of temperature encased in the varying levels of oxygen isotopes in their shells over 10 million year intervals—reveals that eras with relatively high concentrations of greenhouse gases bode ill for the number of species on Earth. "The rule appears to be that greenhouse worlds adversely affect biodiversity," Mayhew says. 

That also bodes ill for the fate of species currently on Earth as the global temperatures continue to rise to levels similar to those seen during the Permian. "The risk of future extinction through rapid global warming is primarily expected to occur through mismatches between the climates to which organisms are adapted in their current range and the future distribution of those climates," Mayhew and his colleagues write in Proceedings of the Royal Society B: Biological Sciences, though it may also be that warmer temperatures lead to less hospitable seas, he adds.

That is not to say that global warming was the cause of this Permian wipeout or that all mass extinctions are associated with warmer worlds—witness the disappearance of 60 percent of different groups of marine organisms during the cooling at the end of the Ordovician period roughly 430 million years ago. But these scientists argue that the evidence of a link between climate change and mass extinctions gives reason to be concerned for the future. "We need to know the mechanism behind the associations and we need to know if associations of this sort also occur in shorter-term climatic fluctuations," Mayhew says. "That will help us decide if this is really a worry for the next generation or if the threat is merely a distant future threat."

Troubling Meaty 'Estrogen'

Troubling Meaty 'Estrogen'

High temperature cooking can imbue meats with a chemical that acts like a hormone

Women take note. Researchers find that a chemical that forms in overcooked meat, especially charred portions, is a potent mimic of estrogen, the primary female sex hormone. That's anything but appetizing, since studies have linked a higher lifetime cumulative exposure to estrogen in women with an elevated risk of breast cancer.  

HORMONAL HAMBURGER? Depending on the temperature at which this burger was grilled—especially how hot its outer surface got—it may have hosted chemical reactions that created PhIP, a carcinogen that has a potent hormonal alter-ego. It can mimic the biological activity of estrogen, the primary female sex hormone.

Indeed, the new finding offers a "biologically plausible" explanation for why diets rich in red meats might elevate breast-cancer risk, notes Nigel J. Gooderham of Imperial College London.

At the very high temperatures reached during frying and charbroiling, natural constituents of meats can undergo chemical reactions that generate carcinogens known as heterocyclic amines. Because these compounds all have very long, unwieldy chemical monikers, most scientists refer to them by their abbreviations, such as IQ, MeIQ, MeIQx, and PhIP.

Of the nearly two dozen different heterocyclic amines that can form, PhIP dominates. It sometimes accumulates in amounts 10 to 50 times higher than that of any other member of this toxic chemical family, Gooderham says. Moreover, he adds, although heterocyclic amines normally cause liver tumors in exposed animals, PhIP is different: "It causes breast cancer in female rats, prostate cancer in male rats, and colon cancer in both." These are the same cancers that in people are associated with eating a lot of cooked meats.

However, the means by which such foods might induce cancer has remained somewhat elusive. So, building on his team's earlier work, Gooderham decided to probe what the heterocyclic amine did in rat pituitary cells. These cells make prolactin—another female sex hormone—but only when triggered by the presence of estrogen. Prolactin, like estrogen, fuels the growth of many breast cancers.

In their new test-tube study, Gooderham and coauthor Saundra N. Lauber show that upon exposure to PhIP, pituitary cells not only make progesterone, but also secrete it. If these cells do the same thing when they're part of the body, those secretions would circulate to other organs—including the breast.

But "what was startling," Gooderham told Science News Online, is that it took just trace quantities of the heterocyclic amine to spur prolactin production. "PhIP was incredibly potent," he says, able to trigger progesterone production at concentrations comparable to what might be found circulating in the blood of people who had eaten a couple of well-done burgers.

The toxicologist cautions that there's a big gap between observing an effect in isolated cells growing in a test-tube and showing that the same holds true in people.

However, even if PhIP does operate similarly in people, he says that's no reason to give up grilled meat. Certain cooking techniques, such as flipping hamburgers frequently, can limit the formation of heterocyclic amines. Moreover, earlier work by the Imperial College team showed that dining on certain members of the mustard family appear to detoxify much of the PhIP that might have inadvertently been consumed as part of a meal.

The human link

Three recent epidemiological studies support concerns about the consumption of grilled meats.

In the first, Harvard Medical School researchers compared the diets of more than 90,000 premenopausal U.S. nurses. Over a 12-year period, 1,021 of the relatively young women developed invasive breast cancers. The more red meat a woman ate, the higher was her risk of developing invasive breast cancer, Eunyoung Cho and her colleagues reported in the Archives of Internal Medicine last November. The increased risk was restricted, however, only to those types of breast cancers that are fueled by estrogen or progesterone.

Overall, women who ate the most red meat—typically 1.5 servings or more per day—faced nearly double the invasive breast-cancer risk of those eating little red meat each week.

Related findings emerged in the April 10 British Journal of Cancer. There, researchers at the University of Leeds reported data from a long-running study of more than 35,000 women in the United Kingdom who ranged in age from roughly 35 to 70. Regardless of the volunteers' age, Janet E. Cade's team found, those who consumed the most meat had the highest risk of breast cancer.

Shortly thereafter, Susan E. Steck of the University of South Carolina's school of public health and her colleagues linked meat consumption yet again with increased cancer risk, but only in the older segment of the women they investigated. By comparing the diets of 1,500 women with breast cancer to those of 1,550 cancerfree women, the scientists showed that postmenopausal women consuming the most grilled, barbecued, and smoked meats faced the highest breast-cancer risk.

These data support accumulating evidence that a penchant for well-done meats can hike a woman's breast-cancer risk, Steck and her colleagues concluded in the May Epidemiology.

PhIP fighters

Such findings have been percolating out of the epidemiology community for years. Nearly a decade ago, for instance, National Cancer Institute scientists reported finding that women who consistently ate their meat very well done—with a crispy, blackened crust—faced a substantially elevated breast-cancer risk when compared to those who routinely ate rare- or medium-cooked meats.

However, even well-done meats without char can contain heterocyclic amines, chemical analyses by others later showed. The compounds' presence appears to correlate best with how meat is cooked, not merely with how brown its interior ended up.

At high temperatures, the simple sugar glucose, together with creatinine—a muscle-breakdown product, and additional free amino acids, can all interact within beef, chicken, and other meats to form heterocyclic amines. In contrast, low-temperature cooking or a quick searing may generate none of the carcinogens.

Because there's no way to tell visually, by taste, or by smell whether PhIP and its toxic kin lace cooked meat, food chemists have been lobbying commercial and home chefs to reduce the heat they use to cook meats—or to turn meats frequently to keep the surfaces closest to the heat source from getting too hot.

The significance of this was driven home to Gooderham several years ago when just such tactics spoiled an experiment he was launching to test whether Brussels sprouts and broccoli could help detoxify PhIP. "I bought 30 kilograms of prime Aberdeen angus lean beef," he recalls. "Then we ground it up and I gave it to a professional cook to turn into burgers and cook." Professional cooks tend to move meats around quite a bit, he found. The result: His expensive, chef-prepared meat contained almost no PhIP.

In the end, he says, "I sacked the cook, bought another 30 kilos of meat and prepared the burgers myself. It was a costly lesson."

Once restarted, however, that study yielded encouraging data.

One way the body detoxifies and sheds toxic chemicals is to link them to what amounts to a sugar molecule. Consumption of certain members of the mustard (Brassica) family, such as broccoli and Brussels sprouts (both members of the B. oleracea species)—can encourage this process. So Gooderham's team fed 250 grams (roughly half a pound) each of broccoli and Brussels sprouts each day to 20 men for almost 2 weeks. On the 12th day, the men each got a cooked-meat meal containing 4.9 micrograms of PhIP.

Compared to similar trial periods when their diets had been Brassica-free, the volunteers excreted up to 40 percent more PhIP in urine, the researchers reported in Carcinogenesis.

Experimental data suggest that two brews may also help detoxify heterocyclic amines. In test-tube studies, white tea largely prevented DNA damage from the heterocyclic amine IQ (SN: 4/15/00, p. 251), and in mice, extracts of beer tackled MeIQx and Trp-P-2.

The best strategy of all, most toxicologists say, is to prevent formation of heterocyclic amines in the first place. In addition to frequently turning meat on the grill or fry pan, partially cooking meats in a microwave prior to grilling will limit the toxic chemicals' formation. So will mixing in a little potato starch to ground beef before grilling or marinating meats with a heavily sugared oil-and-vinegar sauce.