Exceptional Evolutionary Divergence of Human Muscle and Brain Metabolomes Parallels Human Cognitive and Physical Uniqueness

Metabolite concentrations reflect the physiological states of tissues and cells. However, the role of metabolic changes in species evolution is currently unknown. Here, we present a study of metabolome evolution conducted in three brain regions and two non-neural tissues from humans, chimpanzees, macaque monkeys, and mice based on over 10,000 hydrophilic compounds. While chimpanzee, macaque, and mouse metabolomes diverge following the genetic distances among species, we detect remarkable acceleration of metabolome evolution in human prefrontal cortex and skeletal muscle affecting neural and energy metabolism pathways. These metabolic changes could not be attributed to environmental conditions and were confirmed against the expression of their corresponding enzymes. We further conducted muscle strength tests in humans, chimpanzees, and macaques. The results suggest that, while humans are characterized by superior cognition, their muscular performance might be markedly inferior to that of chimpanzees and macaque monkeys.

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Did standing up change our brains?

Although lots of animals are smart, humans are even smarter. How and why do we think and act so differently from other species?

A young boy’s efforts while learning to walk have suggested a new explanation, in a new journal paper jointly authored by his father and grandfather, both academics at the University of Sydney.

In the latest issue of the scientific journal, Frontiers in Neuroscience, the son-and-father team Mac and Rick Shine suggest that the big difference between humans and other species may lie in how we use our brains for routine tasks.

They advance the idea that the key to exploiting the awesome processing power of our brain’s most distinctive feature - the cortex - may have been to liberate it from the drudgery of controlling routine activities.

And that’s where young Tyler Shine, now two years old, comes into the story. When Tyler was first learning to walk, his doting father and grandfather noticed that every step took Tyler’s full attention.

But before too long, walking became routine, and Tyler was able to start noticing other things around him. He was better at maintaining his balance, which freed up his attention to focus on more interesting tasks, like trying to get into mischief.

How did Tyler improve? His father and grandfather suggest that he did so by transferring the control of his balance to ‘lower’ parts of the brain, freeing up the powerful cortex to focus on unpredictable challenges, such as a bumpy floor covered in stray toys.

"Any complicated task - like driving a car or playing a musical instrument - starts out consuming all our attention, but eventually becomes routine," Mac Shine says.

"Studies of brain function suggest that we shift the control of these routine tasks down to ‘lower’ areas of the brain, such as the basal ganglia and the cerebellum.

"So, humans are smart because we have automated the routine tasks; and thus, can devote our most potent mental faculties to deal with new, unpredictable challenges.

"What event in the early history of humans made us change the way we use our brains?

Watching Tyler learn to walk suggested that it was the evolutionary shift from walking on all fours, to walking on two legs.

"Suddenly our brains were overwhelmed with the complicated challenge of keeping our balance - and the best kind of brain to have, was one that didn’t waste its most powerful functions on controlling routine tasks."

So, the Shines believe, those first pre-humans who began to stand upright faced a new evolutionary pressure not just on their bodies, but on their brains as well.

"New technologies are allowing us to look inside the brain while it works, and we are learning an enormous amount," Mac Shine says.

"But in order to interpret those results, we need new ideas as well. I’m delighted that my son has played a role in suggesting one of those ideas."

"Hopefully, by the time he is watching his own son learn to walk, we will be much closer to truly understanding the greatest mystery of human existence: how our brains work."

Primates and patience — the evolutionary roots of self control

A chimpanzee will wait more than two minutes to eat six grapes, but a black lemur would rather eat two grapes now than wait any longer than 15 seconds for a bigger serving.

It’s an echo of the dilemma human beings face with a long line at a posh restaurant. How long are they willing to wait for the five-star meal? Or do they head to a greasy spoon to eat sooner?

A paper published today in the scientific journal Proceedings of the Royal Society B explores the evolutionary reasons why some primate species wait for a bigger reward, while others are more likely to grab what they can get immediately.

"Natural selection has shaped levels of patience to deal with the types of problems that animals face in the wild," said author Jeffrey R. Stevens, a comparative psychologist at the University of Nebraska-Lincoln and the study’s lead author. "Those problems are species-specific, so levels of patience are also species-specific."

Studying 13 primate species, from massive gorillas to tiny marmosets, Stevens compared species’ characteristics with their capacity for “intertemporal choice.” That’s a scientific term for what some might call patience, self-control or delayed gratification.

He found the species with bigger body mass, bigger brains, longer lifespans and larger home ranges also tend to wait longer for a bigger reward.

Chimpanzees, which typically weigh about 85 pounds, live nearly 60 years and range about 35 square miles, waited for a reward for about two minutes, the longest of any of the primate species studied. Cotton-top tamarins, which weigh less than a pound and live about 23 years, waited about eight seconds before opting for a smaller, immediate reward.

The findings are based partially on experiments Stevens performed during the past ten years with lemurs, marmosets, tamarins, chimpanzees and bonobos at Harvard’s Department of Psychology and at the Berlin and Leipzig zoos in Germany. In those experiments, individual animals chose between a tray containing two grapes that they could eat immediately and a tray containing six grapes they could eat after waiting. The wait times were gradually increased until the animal reached an “indifference point” when it opted for the smaller, immediate reward instead of waiting.

Stevens combined those results with those of scientists who performed similar experiments with other primates. He scoured primate-research literature to gather data on the biological characteristics of each species.

In addition to characteristics related to body mass, Stevens analyzed but found no correlation with two other hypotheses for patience: cognitive ability and social complexity.

"In humans, the ability to wait for delayed rewards correlates with higher performance in cognitive measures such as IQ, academic success, standardized test scores and working memory capacity," he wrote. "The cognitive ability hypothesis predicts that species with higher levels of cognition should wait longer than those with lower levels."

But Stevens found no correlation between patience levels and an animal’s relative brain size compared to its body size, the measure he used to quantify cognitive ability.

Researchers also have argued that animals in complex social groups have reduced impulsivity and more patience to adapt to the social hierarchies of dominance and submission. But Stevens did not find correlations between species’ social group sizes and their patience levels.

Stevens said he believes metabolic rates may be the driving factor connecting patience with body mass and related physical characteristics. Smaller animals tend to have higher metabolic rates.

"You need fuel and you need it at a certain rate," he said. "The faster you need it, the shorter time you will wait."

Metabolic rates also may factor in human beings’ willingness to wait. Stevens said human decisions about food, their environment, their health care and even their finances all relate to future payoffs. The mental processes behind those decisions have not yet been well identified.

"To me, this offers us interesting avenues to start thinking about what factors might influence human patience," he said. "What does natural selection tell us about decision making? That applies to humans as well as to other animals."

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Neanderthals were not inferior to modern humans

If you think Neanderthals were stupid and primitive, it’s time to think again.

The widely held notion that Neanderthals were dimwitted and that their inferior intelligence allowed them to be driven to extinction by the much brighter ancestors of modern humans is not supported by scientific evidence, according to a researcher at the University of Colorado Boulder. 

Neanderthals thrived in a large swath of Europe and Asia between about 350,000 and 40,000 years ago. They disappeared after our ancestors, a group referred to as “anatomically modern humans,” crossed into Europe from Africa.

In the past, some researchers have tried to explain the demise of the Neanderthals by suggesting that the newcomers were superior to Neanderthals in key ways, including their ability to hunt, communicate, innovate and adapt to different environments.  

But in an extensive review of recent Neanderthal research, CU-Boulder researcher Paola Villa and co-author Wil Roebroeks, an archaeologist at Leiden University in the Netherlands, make the case that the available evidence does not support the opinion that Neanderthals were less advanced than anatomically modern humans. Their paper was published in the journal PLOS ONE.

"The evidence for cognitive inferiority is simply not there,” said Villa, a curator at the University of Colorado Museum of Natural History. “What we are saying is that the conventional view of Neanderthals is not true."

Villa and Roebroeks scrutinized nearly a dozen common explanations for Neanderthal extinction that rely largely on the notion that the Neanderthals were inferior to anatomically modern humans. These include the hypotheses that Neanderthals did not use complex, symbolic communication; that they were less efficient hunters who had inferior weapons; and that they had a narrow diet that put them at a competitive disadvantage to anatomically modern humans, who ate a broad range of things.

The researchers found that none of the hypotheses were supported by the available research. For example, evidence from multiple archaeological sites in Europe suggests that Neanderthals hunted as a group, using the landscape to aid them.

Researchers have shown that Neanderthals likely herded hundreds of bison to their death by steering them into a sinkhole in southwestern France. At another site used by Neanderthals, this one in the Channel Islands, fossilized remains of 18 mammoths and five woolly rhinoceroses were discovered at the base of a deep ravine. These findings imply that Neanderthals could plan ahead, communicate as a group and make efficient use of their surroundings, the authors said.

Other archaeological evidence unearthed at Neanderthal sites provides reason to believe that Neanderthals did in fact have a diverse diet. Microfossils found in Neanderthal teeth and food remains left behind at cooking sites indicate that they may have eaten wild peas, acorns, pistachios, grass seeds, wild olives, pine nuts and date palms depending on what was locally available.

Additionally, researchers have found ochre, a kind of earth pigment, at sites inhabited by Neanderthals, which may have been used for body painting. Ornaments have also been collected at Neanderthal sites. Taken together, these findings suggest that Neanderthals had cultural rituals and symbolic communication.

Villa and Roebroeks say that the past misrepresentation of Neanderthals’ cognitive ability may be linked to the tendency of researchers to compare Neanderthals, who lived in the Middle Paleolithic, to modern humans living during the more recent Upper Paleolithic period, when leaps in technology were being made.

“Researchers were comparing Neanderthals not to their contemporaries on other continents but to their successors,” Villa said. “It would be like comparing the performance of Model T Fords, widely used in America and Europe in the early part of the last century, to the performance of a modern-day Ferrari and conclude that Henry Ford was cognitively inferior to Enzo Ferrari.”

Although many still search for a simple explanation and like to attribute the Neanderthal demise to a single factor, such as cognitive or technological inferiority, archaeology shows that there is no support for such interpretations, the authors said.

But if Neanderthals were not technologically and cognitively disadvantaged, why didn’t they survive?

The researchers argue that the real reason for Neanderthal extinction is likely complex, but they say some clues may be found in recent analyses of the Neanderthal genome over the last several years. These genomic studies suggest that anatomically modern humans and Neanderthals likely interbred and that the resulting male children may have had reduced fertility. Recent genomic studies also suggest that Neanderthals lived in small groups. All of these factors could have contributed to the decline of the Neanderthals, who were eventually swamped and assimilated by the increasing numbers of modern immigrants.

(Image: Reconstruction by Kennis & Kennis / Photograph by Joe McNally)

Turning science on its head

Harvard neuroscientists have made a discovery that turns 160 years of neuroanatomy on its head.

Myelin, the electrical insulating material in the body long known to be essential for the fast transmission of impulses along the axons of nerve cells, is not as ubiquitous as thought, according to new work led by Professor Paola Arlotta of the Harvard Stem Cell Institute (HSCI) and the University’s Department of Stem Cell and Regenerative Biology, in collaboration with Professor Jeff Lichtman of Harvard’s Department of Molecular and Cellular Biology.

“Myelin is a relatively recent invention during evolution,” says Arlotta. “It’s thought that myelin allowed the brain to communicate really fast to the far reaches of the body, and that it has endowed the brain with the capacity to compute higher-level functions.”

In fact, loss of myelin is a feature in a number of devastating diseases, including multiple sclerosis and schizophrenia.

But the new research shows that despite myelin’s essential roles in the brain, “some of the most evolved, most complex neurons of the nervous system have less myelin than older, more ancestral ones,” said Arlotta, co-director of the HSCI neuroscience program.

What this means, she said, is that the higher one looks in the cerebral cortex — closer to the top of the brain, which is its most evolved part — the less myelin one finds.  Not only that, but “neurons in this part of the brain display a brand-new way of positioning myelin along their axons that has not been previously seen. They have ‘intermittent myelin’ with long axon tracts that lack myelin interspersed among myelin-rich segments.”

“Contrary to the common assumptions that neurons use a universal profile of myelin distribution on their axons, the work indicates that different neurons choose to myelinate their axons differently,” Arlotta said. “In classic neurobiology textbooks, myelin is represented on axons as a sequence of myelinated segments separated by very short nodes that lack myelin. This distribution of myelin was tacitly assumed to be always the same, on every neuron, from the beginning to the end of the axon. This new work finds this not to be the case.”

The results of the research by Arlotta and postdoctoral fellow Giulio Srubek Tomassy, the first author on the report, are published in the latest edition of the journal Science.

The paper is accompanied by a “perspective” by R. Douglas Fields of the Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health, who said that Arlotta and Tomassy’s findings raise important questions about the purpose of myelin, and “are likely to spark new concepts about how information is transmitted and integrated in the brain.”

Arlotta and Tomassy collaborated closely on the new work with postdoctoral fellow Daniel Berger of the Lichtman lab, which generated one of the two massive electron microscopy databases that made the work possible.

“The fact that it is the most evolved neurons, the ones that have expanded dramatically in humans, suggest that what we’re seeing might be the ‘future.’ As neuronal diversity increases and the brain needs to process more and more complex information, neurons change the way they use myelin to achieve more,” said Arlotta.

Tomassy said it is possible that these profiles of myelination “may be giving neurons an opportunity to branch out and ‘talk’ to neighboring neurons.” For example, because axons cannot make synaptic contacts when they are myelinated, one possibility is that these long myelin gaps may be needed to increase neuronal communication and synchronize responses across different neurons. He and Arlotta postulate that the intermittent myelin may be intended to fine-tune the electrical impulses traveling along the axons, in order to allow the emergence of highly complex neuronal behaviors.

Even if there was no God, even if human beings had no soul, it would still be true that evolution had created a remarkable animal — the human animal — during its millions of years of labor. So very like our closest biological relatives, the chimpanzees, yet so different. For our study of the chimpanzees had helped to pinpoint not only the similarities between them and us, but also those ways in which we are most different. Admittedly, we are not the only beings with personalities, reasoning powers, altruism, and emotions like joy and sorrow; nor are we the only beings capable of mental as well as physical suffering. But our intellect has grown mighty in complexity since the first true men branched off from the ape-man stock some two million years ago. And we, and only we, have developed a sophisticated spoken language. For the first time in evolution, a species evolved that was able to teach its young about objects and events not present, to pass on wisdom gleaned from the successes — and the mistakes — of the past, to make plans for the distant future, to discuss ideas so that they could grow, sometimes out of all recognition, through the combined wisdom of the group.

Happy 80th Birthday, Jane Goodall: The Beloved Primatologist on Science, Religion, and Our Human Responsibilities

Findings Could Help Explain Origins of Human Limb Control

We might have more in common with a lamprey than we think, according to a new Northwestern University study on locomotion. At its core, the study of transparent zebrafish addresses a fundamental evolution issue: How did we get here?

Neuroscientists Martha W. Bagnall and David L. McLean have found that the spinal cord circuits that produce body bending in swimming fish are more complicated than previously thought.

Vertebrate locomotion has evolved from the simple left-right bending of the body exemplified by lampreys to the appearance of fins in bony fish to the movement of humans, with the complex nerve and muscle coordination necessary to move four limbs.

Bagnall and McLean report that differential control of an animal’s musculature — the basic template for controlling more complex limbs — is already in place in the spinal networks of simple fish. Neural circuits in zebrafish are completely segregated: individual neurons map to specific muscles.

Specifically, the neural circuits that drive muscle movement on the dorsal (or back) side are separate from the neural circuits activating muscles on the ventral (or front) side. This is in addition to the fish being able to separately control the left and right sides of its body [Video]

Ultimately, understanding more about how fish swim will allow scientists to figure out how humans walk.

“Evolution builds on pre-existing patterns, and this is a critical piece of the puzzle,” McLean said. “Our data help clarify how the transition from water to land could have been accomplished by simple changes in the connections of spinal networks.”

The findings will be published Jan. 10 in the journal Science. McLean, an assistant professor of neurobiology in the Weinberg College of Arts and Sciences, and Bagnall, a postdoctoral fellow in his research group who made the discovery, are authors of the paper.

“This knowledge will put us in a better position to devise more effective therapies for when things go wrong with neural circuits in humans, such as spinal cord damage,” McLean said. “If you want to fix something, you have to know how it works in the first place. Given that the fish spinal cord works in a similar fashion to our own, this makes it a fantastic model system for research.”

McLean and Bagnall studied the motor neurons of baby zebrafish because the fish develop quickly and are see-through. They used state-of-art imaging techniques to monitor and manipulate neuronal activity in the fish.

“You can stare right into the nervous system,” McLean said. “It’s quite remarkable.”

The separate circuits for moving the left and right and top and bottom of the fish allow the animal to twist its body upright when it senses that it has rolled too far to one side or the other.

“This arrangement is perfectly suited to provide rapid postural control during swimming,” Bagnall said. “Importantly, this ancestral pattern of spinal cord organization may also represent an early functional template for the origins of limb control.”

Separate control of dorsal and ventral muscles in the fish body is a possible predecessor to separate control of extensors and flexors in human limbs. By tweaking the connections between these circuits as they elaborated during evolution, it is easier to explain how more complicated patterns of motor coordination in the limbs and trunk could have arisen during dramatic evolutionary changes in the vertebrate body plan, the researchers said.

“We are teasing apart basic components of locomotor circuits,” McLean said. “The molecular mechanisms responsible for building spinal circuits are conserved in all animals, so this study provides a nice hypothesis that scientists can test.”

In the Human Brain, Size Really Isn’t Everything

There are many things that make humans a unique species, but a couple stand out. One is our mind, the other our brain.

The human mind can carry out cognitive tasks that other animals cannot, like using language, envisioning the distant future and inferring what other people are thinking.

The human brain is exceptional, too. At three pounds, it is gigantic relative to our body size. Our closest living relatives, chimpanzees, have brains that are only a third as big.

Scientists have long suspected that our big brain and powerful mind are intimately connected. Starting about three million years ago, fossils of our ancient relatives record a huge increase in brain size. Once that cranial growth was underway, our forerunners started leaving behind signs of increasingly sophisticated minds, like stone tools and cave paintings.

But scientists have long struggled to understand how a simple increase in size could lead to the evolution of those faculties. Now, two Harvard neuroscientists, Randy L. Buckner and Fenna M. Krienen, have offered a powerful yet simple explanation.

In our smaller-brained ancestors, the researchers argue, neurons were tightly tethered in a relatively simple pattern of connections. When our ancestors’ brains expanded, those tethers ripped apart, enabling our neurons to form new circuits.

Dr. Buckner and Dr. Krienen call their idea the tether hypothesis, and present it in a paper in the December issue of the journal Trends in Cognitive Sciences.

“I think it presents some pretty exciting ideas,” said Chet C. Sherwood, an expert on human brain evolution at George Washington University who was not involved in the research.

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Study finds crocodiles are cleverer than previously thought

Turns out the crocodile can be a shrewd hunter himself. A University of Tennessee, Knoxville, researcher has found that some crocodiles use lures to hunt their prey.

Vladimir Dinets, a research assistant professor in the Department of Psychology, is the first to observe two crocodilian species—muggers and American alligators—using twigs and sticks to lure birds, particularly during nest-building time.

The research is published in the current edition of Ethology, Ecology and Evolution. Dinets’ research is the first report of tool use by any reptiles, and also the first known case of predators timing the use of lures to a seasonal behavior of the prey—nest-building.

Dinets first observed the behavior in 2007 when he spotted crocodiles lying in shallow water along the edge of a pond in India with small sticks or twigs positioned across their snouts. The behavior potentially fooled nest-building birds wading in the water for sticks into thinking the sticks were floating on the water. The crocodiles remained still for hours and if a bird neared the stick, they would lunge.

To see if the stick-displaying was a form of clever predation, Dinets and his colleagues performed systematic observations of the reptiles for one year at four sites in Louisiana, including two rookery and two nonrookery sites. A rookery is a bird breeding ground. The researchers observed a significant increase in alligators displaying sticks on their snouts from March to May, the time birds were building nests. Specifically, the reptiles in rookeries had sticks on their snouts during and after the nest-building season. At non-rookery sites, the reptiles used lures during the nest-building season.

"This study changes the way crocodiles have historically been viewed," said Dinets. "They are typically seen as lethargic, stupid and boring but now they are known to exhibit flexible multimodal signaling, advanced parental care and highly coordinated group hunting tactics."

The observations could mean the behavior is more widespread within the reptilian group and could also shed light on how crocodiles’ extinct relatives—dinosaurs—behaved.

"Our research provides a surprising insight into previously unrecognized complexity of extinct reptile behavior," said Dinets. "These discoveries are interesting not just because they show how easy it is to underestimate the intelligence of even relatively familiar animals, but also because crocodilians are a sister taxon of dinosaurs and flying reptiles."

Dinets collaborated with J.C and J.D. Brueggen from the St. Augustine Alligator Farm Zoological Park in St. Augustine, Fla. More of his crocodile research can be found in his book “Dragon Songs.”