lunes, 28 de agosto de 2017

How Neanderthals Gave Us Secret Power

Interbreeding with our fellow hominins appears to have helped humans survive harsh climates.

· MAY 31, 2016

Native Tibetans make use of a gene derived from Denisovans to stay healthy at high altitudes.

By EMILY SINGER

TEXT SIZE

Early human history was a promiscuous affair. As modern humans began to spread out of Africa roughly 50,000 years ago, they encountered other species that looked remarkably like them—the Neanderthals and Denisovans, two groups of archaic humans that shared an ancestor with us roughly 600,000 years earlier. This motley mix of humans coexisted in Europe for at least 2,500 years, and we now know that they interbred, leaving a lasting legacy in our DNA.

The DNA of non-Africans is made up of roughly 1 to 2 percent Neanderthal DNA, and some Asian and Oceanic island populations have as much as 6 percent Denisovan DNA.

Over the last few years, scientists have dug deeper into the Neanderthal and Denisovan sections of our genomes and come to a surprising conclusion. Certain Neanderthal and Denisovan genes seem to have swept through the modern human population—one variant, for example, is present in 70 percent of Europeans—suggesting that these genes brought great advantage to their bearers and spread rapidly.

“In some spots of our genome, we are more Neanderthal than human,” said Joshua Akey, a geneticist at the University of Washington. “It seems pretty clear that at least some of the sequences we inherited from archaic hominins were adaptive, that they helped us survive and reproduce.”

But what, exactly, do these fragments of Neanderthal and Denisovan DNA do? What survival advantage did they confer on our ancestors? Scientists are starting to pick up hints. Some of these genes are tied to our immune system, to our skin and hair, and perhaps to our metabolism and tolerance for cold weather, all of which might have helped emigrating humans survive in new lands.

“What allowed us to survive came from other species,” said Rasmus Nielsen, an evolutionary biologist at the University of California, Berkeley. “It’s not just noise, it’s a very important substantial part of who we are.

Illustration by Lucy Reading-Ikkanda for Quanta Magazine, based on a map by Sriram Sankararaman.

* * *

The Tibetan plateau is a vast stretch of high-altitude real estate isolated by massive mountain ranges. The scant oxygen at 14,000 feet—roughly 40 percent lower than the concentrations at sea level—makes it a harsh environment. People who move there suffer higher rates of miscarriage, blood clots, and stroke on account of the extra red blood cells their bodies produce to feed oxygen-starved tissue.

Native Tibetans, however, manage just fine. Despite the meager air, they don’t make as many red blood cells as the rest of us would at those altitudes, which helps to protect their health.

In 2010, scientists discovered that Tibetans owe their tolerance of low oxygen levels in part to an unusual variant in a gene known as EPAS1. About 90 percent of the Tibetan population and a smattering of Han Chinese (who share a recent ancestor with Tibetans) carry the high-altitude variant. But it’s completely absent from a database of 1,000 human genomes from other populations.

The unique gene then flourished in those who lived at high altitudes and faded away in descendants who colonized less harsh environments.

In 2014, Nielsen and colleagues found that Tibetans or their ancestors likely acquired the unusual DNA sequence from Denisovans, a group of early humans first described in 2010 that are more closely related to Neanderthals than to us.

The unique gene then flourished in those who lived at high altitudes and faded away in descendants who colonized less harsh environments. “That’s one of the most clear-cut examples of how [interbreeding] can lead to adaptation,” said Sriram Sankararaman, a geneticist and computer scientist at the University of California, Los Angeles.

The idea that closely related species can benefit from interbreeding, known in evolutionary terms as adaptive introgression, is not a new one. As a species expands into a new territory, it grapples with a whole new set of challenges—different climate, food, predators, and pathogens.

Species can adapt through traditional natural selection, in which spontaneous mutations that happen to be helpful gradually spread through the population. But such mutations strike rarely, making it a very slow process. A more expedient option is to mate with species that have already adapted to the region and co-opt some of their helpful DNA. (Species are traditionally defined by their inability to mate with one another, but closely related species often interbreed.)

This phenomenon has been well documented in a number of species, including mice that adopted other species’ tolerance to pesticides and butterflies that appropriated other species’ wing patterning. But it was difficult to study adaptive introgression in humans until the first Neanderthal genome was sequenced in 2010, providing scientists with hominin DNA to compare to our own.

Neanderthals and Denisovans would have been a good source of helpful DNA for our ancestors. They had lived in Europe and Asia for hundreds of thousands of years—enough time to adjust to the cold climate, weak sun and local microbes. “What better way to quickly adapt than to pick up a gene variant from a population that had probably already been there for 300,000 years?” Akey said.

Indeed, the Neanderthal and Denisovan genes with the greatest signs of selection in the modern human genome “largely have to do with how humans interact with the environment,” he said.

Illustration by Lucy Reading-Ikkanda for Quanta Magazine, based on a map by Sriram Sankararaman.

To find these adaptive segments, scientists search the genomes of contemporary humans for regions of archaic DNA that are either more common or longer than expected. Over time, useless pieces of Neanderthal DNA—those that don’t help the carrier—are likely to be lost. And long sections of archaic DNA are likely to be split into smaller segments unless there is selective pressure to keep them intact.

In 2014, two groups, one led by Akey and the other by David Reich, a geneticist at Harvard Medical School, independently published genetic maps that charted where in our genomes Neanderthal DNA is most likely to be found. To Akey’s surprise, both maps found that the most common adaptive Neanderthal-derived genes are those linked to skin and hair growth. One of the most striking examples is a gene called BNC2, which is linked to skin pigmentation and freckling in Europeans.

Nearly 70 percent of Europeans carry the Neanderthal version.

Scientists surmise that BNC2 and other skin genes helped modern humans adapt to northern climates, but it’s not clear exactly how. Skin can have many functions, any one of which might have been helpful. “Maybe skin pigmentation, or wound healing, or pathogen defense, or how much water loss you have in an environment, making you more or less susceptible to dehydration,” Akey said. “So many potential things could be driving this—we don’t know what differences were most important.”

* * *

One of the deadliest foes that modern humans had to fight as they ventured into new territories was also the smallest—novel infectious diseases for which they had no immunity. “Pathogens are one of the strongest selective forces out there,” said Janet Kelso, a bioinformatician at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany.

Earlier this year, Kelso and collaborators identified a large stretch of Neanderthal DNA—143,000 DNA base-pairs long—that may have played a key role in helping modern humans fight off disease. The region spans three different genes that are part of the innate immune system, a molecular surveillance system that forms the first line of defense against pathogens. These genes produce proteins called toll-like receptors, which help immune cells detect foreign invaders and trigger the immune system to attack.

Modern humans can have several different versions of this stretch of DNA. But at least three of the variants appear to have come from archaic humans—two from Neanderthals and one from Denisovans.

To figure out what those variants do, Kelso’s team scoured public databases housing reams of genomic and health data. They found that people carrying one of the Neanderthal variants are less likely to be infected with H. pylori, a microbe that causes ulcers, but more likely to suffer from common allergies such as hay fever.

Kelso speculates that this variant might have boosted early humans’ resistance to different kinds of bacteria. That would have helped modern humans as they colonized new territories. Yet this added resistance came at a price. “The trade-off for that was a more sensitive immune system that was more sensitive to nonpathogenic allergens,” said Kelso.

But she was careful to point out that this is just a theory. “At this point, we can hypothesize a lot, but we don’t know exactly how this is working.”

Most of the Neanderthal and Denisovan genes found in the modern genome are more mysterious. Scientists have only a vague idea of what these genes do, let alone how the Neanderthal or Denisovan version might have helped our ancestors. “It’s important to understand the biology of these genes better, to understand what selective pressures were driving the changes we see in present-day populations,” Akey said.

A number of studies like Kelso’s are now under way, trying to link Neanderthal and Denisovan variants frequently found in contemporary humans with specific traits, such as body-fat distribution, metabolism or other factors.

One study of roughly 28,000 people of European descent, published in Science in February, matched archaic gene variants with data from electronic health records. Overall, Neanderthal variants are linked to higher risk of neurological and psychiatric disorders and lower risk of digestive problems. (That study didn’t focus on adaptive DNA, so it’s unclear how the segments of archaic DNA that show signs of selection affect us today.)

At present, much of the data available for such studies is weighted toward medical problems—most of these databases were designed to find genes linked to diseases such as diabetes or schizophrenia. But a few, such as the U.K. Biobank, are much broader, storing information on participants’ vision, cognitive test scores, mental health assessments, lung capacity and fitness.

Direct-to-consumer genetics companies also have large, diverse data sets. For example, 23andMe analyzes users’ genetics for clues about ancestry, health risk and other sometimes bizarre traits, such as whether they have a sweet tooth or a unibrow.

Of course, not all the DNA we got from Neanderthals and Denisovans was good. The majority was probably detrimental. Indeed, we tend to have less Neanderthal DNA near genes, suggesting that it was weeded out by natural selection over time. Researchers are very interested in these parts of our genomes where archaic DNA is conspicuously absent.

“There are some really big places in the genome with no Neanderthal or Denisovan ancestry as far as we can see—some process is purging the archaic material from these regions,” Sankararaman said. “Perhaps they are functionally important for modern humans.”

SOURCE: https://www.quantamagazine.org/how-neanderthal-dna-helps-humanity-20160526/?utm_source=Quanta+Magazine&utm_campaign=510f4dd932-EMAIL_CAMPAIGN_2017_08_24&utm_medium=email&utm_term=0_f0cb61321c-510f4dd932-389390733

sábado, 19 de agosto de 2017

SCIENTIFIC AMERICAN REVIEW STATES.......

White Nationalists Are Flocking to Genetic Ancestry Tests--with Surprising Results

Sometimes they find they are not as “white” as they’d hoped

By Eric Boodman, STAT on August 16, 2017

It was a strange moment of triumph against racism: The gun-slinging white supremacist Craig Cobb, dressed up for daytime TV in a dark suit and red tie, hearing that his DNA testing revealed his ancestry to be only “86 percent European, and … 14 percent Sub-Saharan African.” The studio audience whooped and laughed and cheered. And Cobb—who was, in 2013, charged with terrorizing people while trying to create an all-white enclave in North Dakota—reacted like a sore loser in the schoolyard.

“Wait a minute, wait a minute, hold on, just wait a minute,” he said, trying to put on an all-knowing smile. “This is called statistical noise.”

Then, according to the Southern Poverty Law Center, he took to the white nationalist website Stormfront to dispute those results. That’s not uncommon: With the rise of spit-in-a-cup genetic testing, there’s a trend of white nationalists using these services to prove their racial identity, and then using online forums to discuss the results.

But like Cobb, many are disappointed to find out that their ancestry is not as “white” as they’d hoped. In a new study, sociologists Aaron Panofsky and Joan Donovan examined years’ worth of posts on Stormfront to see how members dealt with the news.

It’s striking, they say, that white nationalists would post these results online at all. After all, as Panofsky put it, “they will basically say if you want to be a member of Stormfront you have to be 100 percent white European, not Jewish.”

But instead of rejecting members who get contrary results, Donovan said, the conversations are “overwhelmingly” focused on helping the person to rethink the validity of the genetic test. And some of those critiques—while emerging from deep-seated racism—are close to scientists’ own qualms about commercial genetic ancestry testing.

Panofsky and Donovan presented their findings at a sociology conference in Montreal on Monday. The timing of the talk—some 48 hours after the violent white nationalist rally in Charlottesville, Va.—was coincidental. But the analysis provides a useful, if frightening, window into how these extremist groups think about their genes.

RECKONING WITH RESULTS

Stormfront was launched in the mid-1990s by Don Black, a former grand wizard of the Ku Klux Klan. His skills in computer programming were directly related to his criminal activities: He learned them while in prison for trying to invade the Caribbean island nation of Dominica in 1981, and then worked as a web developer after he got out. That means this website dates back to the early years of the internet, forming a kind of deep archive of online hate.

To find relevant comments in the 12 million posts written by over 300,000 members, the authors enlisted a team at the University of California, Los Angeles, to search for terms like “DNA test,” “haplotype,” “23andMe,” and “National Geographic.” Then the researchers combed through the posts they found, not to mention many others as background. Donovan, who has moved from UCLA to the Data & Society Research Institute, estimated that she spent some four hours a day reading Stormfront in 2016. The team winnowed their results down to 70 discussion threads in which 153 users posted their genetic ancestry test results, with over 3,000 individual posts.

About a third of the people posting their results were pleased with what they found. “Pretty damn pure blood,” said a user with the username Sloth. But the majority didn’t find themselves in that situation. Instead, the community often helped them reject the test, or argue with its results.

Some rejected the tests entirely, saying that an individual’s knowledge about his or her own genealogy is better than whatever a genetic test can reveal. “They will talk about the mirror test,” said Panofsky, who is a sociologist of science at UCLA’s Institute for Society and Genetics. “They will say things like, ‘If you see a Jew in the mirror looking back at you, that’s a problem; if you don’t, you’re fine.'” Others, he said, responded to unwanted genetic results by saying that those kinds of tests don’t matter if you are truly committed to being a white nationalist. Yet others tried to discredit the genetic tests as a Jewish conspiracy “that is trying to confuse true white Americans about their ancestry,” Panofsky said.

But some took a more scientific angle in their critiques, calling into doubt the method by which these companies determine ancestry—specifically how companies pick those people whose genetic material will be considered the reference for a particular geographical group.

And that criticism, though motivated by very different ideas, is one that some researchers have made as well, even as other scientists have used similar data to better understand how populations move and change.

“There is a mainstream critical literature on genetic ancestry tests—geneticists and anthropologists and sociologists who have said precisely those things: that these tests give an illusion of certainty, but once you know how the sausage is made, you should be much more cautious about these results,” said Panofsky.

A COMMUNITY’S GENETIC RULES

Companies like Ancestry.com and 23andMe are meticulous in how they analyze your genetic material. As points of comparison, they use both preexisting datasets as well as some reference populations that they have recruited themselves. The protocol includes genetic material from thousands of individuals, and looks at thousands of genetic variations.

“When a 23andMe research participant tells us that they have four grandparents all born in the same country—and the country isn’t a colonial nation like the U.S., Canada, or Australia—that person becomes a candidate for inclusion in the reference data,” explained Jhulianna Cintron, a product specialist at 23andMe. Then, she went on, the company excludes close relatives, as that could distort the data, and removes outliers whose genetic data don’t seem to match with what they wrote on their survey.

But specialists both inside and outside these companies recognize that the geopolitical boundaries we use now are pretty new, and so consumers may be using imprecise categories when thinking about their own genetic ancestry within the sweeping history of human migration. And users’ ancestry results can change depending on the dataset to which their genetic material is being compared—a fact which some Stormfront users said they took advantage of, uploading their data to various sites to get a more “white” result.

J. Scott Roberts, an associate professor at the University of Michigan, who has studied consumer use of genetic tests and was not involved with the study, said the companies tend to be reliable at identifying genetic variants. Interpreting them in terms of health risk or ancestry, though, is another story. “The science is often murky in those areas and gives ambiguous information,” he said. “They try to give specific percentages from this region, or x percent disease risk, and my sense is that that is an artificially precise estimate.”

For the study authors, what was most interesting was to watch this online community negotiating its own boundaries, rethinking who counts as “white.” That involved plenty of contradictions. They saw people excluded for their genetic test results, often in very nasty (and unquotable) ways, but that tended to happen for newer members of the anonymous online community, Panofsky said, and not so much for longtime, trusted members. Others were told that they could remain part of white nationalist groups, in spite of the ancestry they revealed, as long as they didn’t “mate,” or only had children with certain ethnic groups. Still others used these test results to put forth a twisted notion of diversity, one “that allows them to say, ‘No, we’re really diverse and we don’t need non-white people to have a diverse society,'” said Panofsky.

That’s a far cry from the message of reconciliation that genetic ancestry testing companies hope to promote.

“Sweetheart, you have a little black in you,” the talk show host Trisha Goddard told Craig Cobb on that day in 2013. But that didn’t stop him from redoing the test with a different company, trying to alter or parse the data until it matched his racist worldview.

ABOUT THE AUTHOR(S)

Eric Boodman

Recent Articles

STAT

STAT delivers fast, deep, and tough-minded journalism. We take you inside science labs and hospitals, biotech boardrooms, and political backrooms. We dissect crucial discoveries. We examine controversies and puncture hype. We hold individuals and institutions accountable. We introduce you to the power brokers and personalities who are driving a revolution in human health. These are the stories that matter to us all.

domingo, 13 de agosto de 2017

How Humans Evolved Supersize Brains

Scientists have begun to identify the symphony of biological triggers that powered the extraordinary expansion of the human brain.

Ferris Jabr , Contributing Writer , November 10, 2015

There it was, sitting on the mantelpiece, staring at her with hollow eyes and a naked grin. She could not stop staring back. It looked distinctly like the fossilized skull of an extinct baboon. That was the sort of thing Josephine Salmons was likely to know. At the time — 1924 — she was one of the only female students of anatomy attending the University of the Witwatersrand in South Africa. On this particular day she was visiting her friend Pat Izod, whose father managed a quarry company that had been excavating limestone near the town of Taung. Workers had unearthed numerous fossils during the excavation, and the Izods had kept this one as a memento. Salmons brought news of the skull to her professor, Raymond Dart, an anthropologist with a particular interest in the brain. He was incredulous. Very few primate fossils had been uncovered this far south in Africa. If the Taung site really housed such fossils, it would be an invaluable treasure trove. The next morning Salmons brought Dart the skull, and he could see that she was right: The skull was undeniably simian/

Dart promptly arranged to have other primate fossils from the Taung quarry sent to him. Later that year, as he was preparing to attend a close friend’s wedding, he received a large crate. One of the specimens it contained was so mesmerizing that he nearly missed the ceremony. It came in two pieces: a natural endocast — the fossilized mold of the inner cranium, preserving the brain’s topography — and its matching skeletal face, with eye sockets, nose, jaw and teeth all intact. Dart noticed right away that this was the fossil of an extinct ape, not a monkey. The teeth suggested that the individual had died at age 6 or so. The point where the spinal cord had joined the skull was too far forward for a knuckle walker, indicating bipedalism. And the endocast, which was a little too large for a nonhuman ape of that age, had surface features characteristic of a human brain. After further study, Dart reached a bold conclusion: this was the fossil of a previously unknown ancestor of modern humans — Australopithecus africanus, the “Man-Ape of South Africa.”

Raymond Dart with the Taung child.

New York Public Library / Science Source

At first, the greater scientific community lambasted Dart’s proposal. If the Taung child, as the fossil was nicknamed, truly belonged to a hominin, surely it would have a far larger brain. Its cranium was a bit bigger than that of a chimpanzee, but not by much. Besides, it was generally believed that humans had evolved in Asia, not Africa. The “absurdly tiny” illustration accompanying Dart’s 1925 Nature paper, and his initial possessiveness of the specimen, did not help matters. Eventually, though, as prominent experts got to see the Taung child for themselves, and similar fossil discoveries came to light, attitudes began to change. By the 1950s, anthropologists had accepted that Taung was indeed a hominin and that an exceptionally large brain had not always been a distinguishing characteristic of humans. Dean Falk, a professor of anthropology at Florida State University and an expert on brain evolution, has called the Taung child “one of the most (if not the most) important hominin discoveries of the 20th century.”

In subsequent decades, by uncovering and comparing other fossil skulls and endocasts, paleontologists documented one of the most dramatic transitions in human evolution. We might call it the Brain Boom. Humans, chimps and bonobos split from their last common ancestor between 6 and 8 million years ago. For the next few million years, the brains of early hominins did not grow much larger than those of our ape ancestors and cousins. Starting around 3 million years ago, however, the hominin brain began a massive expansion. By the time our species, Homo sapiens, emerged about 200,000 years ago, the human brain had swelled from about 350 grams to more than 1,300 grams. In that 3-million-year sprint, the human brain almost quadrupled the size its predecessors had attained over the previous 60 million years of primate evolution.

Fossils established the Brain Boom as fact. But they tell us next to nothing about how and why the human brain grew so large so quickly. There are plenty of theories, of course, especially regarding why: increasingly complex social networks, a culture built around tool use and collaboration, the challenge of adapting to a mercurial and often harsh climate — any or all of these evolutionary pressures could have selected for bigger brains.

Although these possibilities are fascinating, they are extremely difficult to test. In the last eight years, however, scientists have started to answer the “how” of human brain expansion — that is, the question of how the supersizing happened on a cellular level and how human physiology reconfigured itself to accommodate a dramatically enlarged and energy-guzzling brain. “It was all speculation up until now, but we finally have the tools to really get some traction,” said Gregory Wray, an evolutionary biologist at Duke University. “What kinds of mutations occurred, and what did they do? We’re starting to get answers and a deeper appreciation for just how complicated this process was.”

What Makes the Human Brain Special

One scientist, in particular, has transformed the way researchers size up brains. Rather than fixating on mass or volume as a proxy for brainpower, she has focused on counting a brain’s constituent parts.

In her laboratory at the Institute of Biomedical Sciences at the Federal University of Rio de Janeiro, Suzana Herculano-Houzelroutinely dissolves brains into a soup of nuclei — cells’ genetic control rooms. Each neuron has one nucleus. By tagging the nuclei with fluorescent molecules and measuring the glow, she can get a precise tally of individual brain cells. Using this method on a wide variety of mammalian brains, she has shown that, contrary to long-standing assumptions, larger mammalian brains do not always have more neurons, and the ones they do have are not always distributed in the same way.

When it comes to brains, size isn’t everything. The human brain is much smaller than that of an elephant or whale. But there are far more neurons in a human’s cerebral cortex than in the cortex of any other animal.

Data taken from the following studies: Cellular scaling rules for primate brains; Cellular scaling rules for rodent brains; Gorilla and Orangutan Brains Conform to the Primate Cellular Scaling Rules: Implications for Human Evolution; The elephant brain in numbers.

Olena Shmahalo/Quanta Magazine; source: BrainMuseum.org and Herculano-Houzel et al.

The human brain has 86 billion neurons in all: 69 billion in the cerebellum, a dense lump at the back of the brain that helps orchestrate basic bodily functions and movement; 16 billion in the cerebral cortex, the brain’s thick corona and the seat of our most sophisticated mental talents, such as self-awareness, language, problem solving and abstract thought; and 1 billion in the brain stem and its extensions into the core of the brain. In contrast, the elephant brain, which is three times the size of our own, has 251 billion neurons in its cerebellum, which helps manage a giant, versatile trunk, and only 5.6 billion in its cortex. Considering brain mass or volume alone masks these important distinctions.

Based on her studies, Herculano-Houzel has concluded that primates evolved a way to pack far more neurons into the cerebral cortex than other mammals did. The great apes are tiny compared to elephants and whales, yet their cortices are far denser: Orangutans and gorillas have 9 billion cortical neurons, and chimps have 6 billion. Of all the great apes, we have the largest brains, so we come out on top with our 16 billion neurons in the cortex. In fact, humans appear to have the most cortical neurons of any species on Earth. “That’s the clearest difference between human and nonhuman brains,” Herculano-Houzel says. It’s all about the architecture, not just size.

The human brain is also unique in its unsurpassed gluttony. Although it makes up only 2 percent of body weight, the human brain consumes a whopping 20 percent of the body’s total energy at rest. In contrast, the chimpanzee brain needs only half that. Researchers have long wondered how the human body adapted to sustain such a uniquely ravenous organ. In 1995, the anthropologist Leslie Aielloand the evolutionary biologist Peter Wheeler proposed the “expensive tissue hypothesis” as a possible answer. The underlying logic is straightforward: Human brain evolution likely required a metabolic trade-off. In order for the brain to grow, other organs, namely the gut, had to shrink, and energy that would typically have gone to the latter was redirected to the former. For evidence, they pointed to data showing that primates with larger brains have smaller intestines.

A few years later, the anthropologist Richard Wrangham built on this idea, arguing that the invention of cooking was crucial to human brain evolution. Soft, cooked foods are much easier to digest than tough raw ones, yielding more calories for less gastrointestinal work. Perhaps, then, learning to cook permitted a bloating of the human brain at the expense of the gut. Other researchers have proposed that similar trade-offs might have occurred between brain and muscle, given how much stronger chimps are than humans.

Collectively, these hypotheses and observations of modern anatomy are compelling. But they are based on the echoes of biological changes that are thought to have occurred millions of years ago. To be certain of what happened, to pinpoint the physiological adaptations that made the brain’s evolutionary growth spurt possible, we will have to dive deeper than flesh, into our very genome.

How does the number of neurons in the cerebral cortex vary with the size of that part of the brain? Different scaling rules apply. In rodents, a 10-fold increase in the number of cortical neurons leads to a 50-fold increase in the size of the cortex. In primates, by contrast, the same neural increase leads to only a 10-fold increase in cortex size — a far more economical relationship.

Olena Shmahalo/Quanta Magazine; source: Herculano-Houzel et. al. (2014)

How Genes Build the Brain

About eight years ago, Wray and his colleagues began to investigate a family of genes that influence the movement of glucose into cells to be used as energy. One member of the gene family is especially active in brain tissue, whereas another is most active in muscle. If the size of the human brain required a metabolic trade-off between brain tissue and muscle, then these genes should behave differently in humans and chimpanzees.

Wray and his team collected brain, muscle and liver samples from deceased humans and chimpanzees and attempted to measure gene activity in each sample. When a cell “expresses” a gene, it translates the DNA first into a signature messenger RNA (mRNA) sequence and subsequently into a chain of amino acids that forms a protein. Varying levels of distinct mRNAs can therefore provide a snapshot of gene activity in a particular type of tissue.

Wray’s team extracted mRNA from the tissues and amplified it many times over in the lab in order to measure the relative abundance of different mRNAs. They found that the brain-centric glucose-transporting gene was 3.2 times more active in human brain tissue than in the chimp brain, whereas the muscle-centric gene was 1.6 times more active in chimp muscle than in human muscle. Yet the two genes behaved similarly in the liver of both species.

Given that the human and chimp gene sequences are nearly identical, something else must explain their variable behavior. Wray and his colleagues found some intriguing differences between the genes’ corresponding regulatory sequences — stretches of DNA that stimulate or stifle gene activity. In humans, but not in chimps, the regulatory sequences for the muscle and brain-focused glucose-transporting genes had accumulated more mutations than would be expected by chance alone, indicating that these regions had undergone accelerated evolution. In other words, there was a strong evolutionary pressure to modify the human regulatory regions in a way that sapped energy from muscle and channeled it to the brain. Genes had corroborated the expensive tissue hypothesis in a way fossils never could.

Last year, the computational biologist Kasia Bozek, who now works at the Okinawa Institute for Science and Technology in Japan, published a similar study that examined metabolism from a different angle. In addition to looking at gene expression, Bozek and her colleagues analyzed levels of metabolites, a diverse group of small molecules that includes sugars, nucleic acids and neurotransmitters. Many metabolites are either necessary for metabolism or produced by it. Different organs have distinct metabolite profiles, depending on what they do and how much energy they require. In general, metabolite levels in the organs of closely related species are more in sync than levels between distantly related species. Bozek found that the metabolite profiles of human and chimp kidneys, for example, were pretty similar. But the variation between chimp and human brain metabolite levels was four times higher than would be expected based on a typical rate of evolution; muscle metabolites differed from the expected levels by a factor of seven. “A single gene can probably regulate a lot of metabolites,” Bozek said. “So even if the difference is not huge at the gene level, you could get a big difference in the metabolite levels.”

“It wasn’t just a couple mutations and — bam! — you get a bigger brain.”

Bozek and her colleagues then pitted 42 humans, including college basketball players and professional rock climbers, against chimpanzees and macaques in a test of strength. All of the primates had to pull a sliding shelf saddled with weights toward themselves. Accounting for body size and weight, the chimps and macaques were twice as strong as the humans. It’s not entirely clear why, but it is possible that our primate cousins get more power out of their muscles than we get out of ours because they feed their muscles more energy. “Compared to other primates, we lost muscle power in favor of sparing energy for our brains,” Bozek said. “It doesn’t mean that our muscles are inherently weaker. We might just have a different metabolism.”

Meanwhile, Wray had turned to his Duke colleague Debra Silver, an expert in embryonic brain development, to embark on a pioneering experiment. Not only were they going to identify relevant genetic mutations from our brain’s evolutionary past, they were also going to weave those mutations into the genomes of lab mice and observe the consequences. “This is something no one had attempted before,” Silver said.

The researchers began by scanning a database of human accelerated regions (HARs); these regulatory DNA sequences are common to all vertebrates but have rapidly mutated in humans. They decided to focus on HARE5, which seemed to control genes that orchestrate brain development. The human version of HARE5 differs from its chimp correlate by 16 DNA letters. Silver and Wray introduced the chimpanzee copy of HARE5 into one group of mice and the human edition into a separate group. They then observed how the embryonic mice brains grew.

After nine days of development, mice embryos begin to form a cortex, the outer wrinkly layer of the brain associated with the most sophisticated mental talents. On day 10, the human version of HARE5 was much more active in the budding mice brains than the chimp copy, ultimately producing a brain that was 12 percent larger. Further tests revealed that HARE5 shortened the time required for certain embryonic brain cells to divide and multiply from 12 hours to nine. Mice with the human HARE5 were creating new neurons more rapidly.

“This sort of study would have been impossible to do 10 years ago when we didn’t have the full genome sequences,” Silver said. “It’s really exciting.” But she also stressed that it will take a great deal more research to fully answer how the human brain blew up. “It’s a mistake to think we can explain brain size with just one or two mutations. I think that is dead wrong. We have probably acquired many little changes that are in some ways coopting the developmental rules.”

Wray concurs: “It wasn’t just a couple mutations and — bam! — you get a bigger brain. As we learn more about the changes between human and chimp brains, we realize there will be lots and lots of genes involved, each contributing a piece to that. The door is now open to get in there and really start understanding. The brain is modified in so many subtle and nonobvious ways.”

Brain and Body

Although the mechanics of the human brain’s expansion have long been mysterious, its importance has rarely been questioned. Again and again, researchers have cited the evolutionary surge in human brain size as the key reason for our exceptionally high degree of intelligence compared to other animals. As recent research on whale and elephant brains makes clear, size is not everything, but it certainly counts for something. The reason we have so many more cortical neurons than our great-ape cousins is not that we have denser brains, but rather that we evolved ways to support brains that are large enough to accommodate all those extra cells.

There’s a danger, though, in becoming too enamored with our own big heads. Yes, a large brain packed with neurons is essential to what we consider high intelligence. But it’s not sufficient. Consider, for a moment, what the world would be like if dolphins had hands. Dolphins are impressively brainy. They have demonstrated self-awareness, cooperation, planning and the rudiments of language and grammar. Compared to apes, though, they are severely limited in their ability to manipulate the world’s raw materials. Dolphins will never enter the Stone Age; flippers cannot finesse.

Similarly, we know that chimps and bonobos can understand human language and even form simple sentences with touch-screen keyboards, but their vocal tracts are inadequate for producing the distinct series of sounds required for speech. Conversely, some birds have the right vocal anatomy to flawlessly mimic human speech, but their brains are not large enough or wired in the right way to master complex language.

No matter how large the human brain grew, or how much energy we lavished upon it, it would have been useless without the right body. Three particularly crucial adaptations worked in tandem with our burgeoning brain to dramatically increase our overall intelligence: bipedalism, which freed up our hands for tool making, fire building and hunting; manual dexterity surpassing that of any other animal; and a vocal tract that allowed us to speak and sing. Human intelligence, then, cannot be traced to a single organ, no matter how large; it emerged from a serendipitous confluence of adaptations throughout the body. Despite our ongoing obsession with the size of our noggins, the fact is that our intelligence has always been so much bigger than our brain.
...................................................................................................................................................

IN THIS SERIES

Life’s Big Leaps: Critical Moments in Evolution

1. Mongrel Microbe Tests Story of Complex Life

2. Life’s Secrets Sought in a Snowflake

3. The Woman Who Stared at Wasps

4. How Humans Evolved Supersize Brains

SOURCE: https://www.quantamagazine.org/how-humans-evolved-supersize-brains-20151110/?utm_source=Quanta+Magazine&utm_campaign=6e1fed74c2-EMAIL_CAMPAIGN_2017_08_10&utm_medium=email&utm_term=0_f0cb61321c-6e1fed74c2-389390733

DOWNLOAD AS PDF This article was reprinted on BusinessInsider.com and Wired.com.