Denisovan

What Neandertal DNA can teach about race, autism, and more?

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london-bicycle-elevated-highway-screenshotPaleoanthropologists used to pray that they would unearth big troves of intact Neandertal skeletons and well-preserved artifacts that they could comb for clues to the origins of the human race. But these days, they can often get as much or more information straight from the DNA in bone fragments.

Case in point: the newly published genome study in Science from Matthias Meyer and Svante Pääbo of the Max Planck Institute for Evolutionary Anthropology and their international team of colleagues. Using a novel DNA sequencing technique that works particularly well with degraded specimens, they examined the genome of a seven-year-old girl who died more than 74,000 years ago, using a surviving sliver from one of her finger bones. That girl’s bone fragment was one of the few pieces of evidence that in 2010 revealed the existence of the ancient Denisovan people — contemporaries of the Neandertals who overlapped with them in eastern Asia.

 

Matthias Meyer at work in the laboratory. (Credit: Max Planck Inst. for Evol. Anthro.)

Yet from that extraordinarily humble source, the Max Planck scientists have drawn a wealth of insights. They learned, for instance, that the Denisovans were probably dark-skinned, unlike the pale Neandertals. Because the girl had two X chromosomes, one from each parent, the scientists were able to infer that the Denisovan population had relatively little genetic diversity. Living natives of Papua New Guinea, Australia, and some southeast Asian islands derived about 6 percent of their genes from the Denisovans, yet the Denisovans seem to have contributed nothing of lasting value to the DNA of people in other parts of the world. Comparison with the Denisovan DNA also allowed the researchers to recognize that Europeans carry somewhat fewer genes from Neandertals than do East Asians and Native Americans.

Such discoveries are endlessly fascinating to some of us. But I can also understand that many people might reasonably question why any of these details matter. After all, Neandertals and our other ancient ancestors have been extinct for 30,000 years or longer. Why should we care so much about their DNA? Is there any practical value to be had from these studies?

I’ll argue that there is, and that it might be especially useful in helping us to develop more enlightened attitudes about racial differences and autism. To explain why, it may be useful to start by reviewing some of the major current ideas about how humans evolved in the first place.

Overview of our origins

Fifteen or 20 years ago, it might have been easier to find a rough consensus among paleoanthropologists about this topic than it is today precisely because of the recent bounty of fossil and DNA discoveries. All that information has answered some important questions and filled in a level of detail that might once have seemed inconceivable, but curiously enough, some of the broad strokes in the big picture have become less clear.

Roughly speaking, in Africa 1.7-2 million years ago, the earliest primitive members of the genus Homo appeared. They were small, hairy people who might look a bit apelike by our standards of beauty, but they had bigger brains and more tools than the upright Australopithecus species before them. The Homo erectus people were successful enough to spread out of Africa and migrate across Asia, and are responsible for some of the ancient fossils given names such as “Peking man.” Nevertheless, they were probably something of a false start for the spread of humanity as we now it.

 

The more relevant development came between 400,000 and 800,000 years ago, with a new wave of African emigration into the Middle East and Asia by a group of people with even bigger brains and better tools. They gave rise to the brawny, brow-ridged Neandertal people, Europe’s first inhabitants. Yet they also spawned at least one other Asian group, the Denisovans. (It wouldn’t be too surprising anymore if still more sibling groups contemporary to the Neandertals and Denisovans turned up elsewhere in Asia.) Meanwhile, humans also continued to prosper and evolve in Africa, and by 80,000 years ago, ones with a fully modern appearance had appeared and started their own exodus into the rest of the Old World.

What happened next is the stuff of archaeologists’ heated arguments. The oldest theory is the multiregional hypothesis strongly advocated by Milford Wolpoff of the University of Michigan in Ann Arbor. It claims that as different in appearance as moderns, Neandertals, Denisovans, and even the early Homo erectus might seem, they were all still members of the same human species. Over time, the modern traits predominated but some of the traits in local populations that had adaptive value (such as shorter, thicker bodies in cold climates) were retained and might bear some connection to physical differences seen in populations around the world today.

In the 1980s, however, a starkly opposing theory emerged largely, though not exclusively, from studies of mitochondrial DNA in living populations. (Mitochondria, the organelles in animal cells that create chemical energy, carry their own unique sets of genes, completely separate from the DNA in the nucleus for the rest of the cell’s genes.) Those analyses suggested that the maternal bloodlines of everyone alive today converged back on Africa less than 100,000 years ago, with no trace of a genetic contribution from local groups elsewhere. That conclusion spawned the “out of Africa” model, according to which scientists such as Chris Stringer of the Natural History Museum in London argued that when the anatomically modern humans colonized Asia and Europe, they displaced the Neandertals and other ancient residents without breeding with them. Whether the moderns had directly exterminated the ancients or simply outcompeted them for resources was anybody’s guess, but interbreeding was effectively nonexistent.

The out-of-Africa model and its mitochondrial DNA evidence proved highly persuasive to many anthropologists. Disagreements remained fierce, but during the 1990s it was often presented as the default explanation for human origins, even though almost everyone acknowledged how counterintuitive it seemed that modern humans would so completely refrain from mixing with creatures that looked so much like them. Mostly, scientists chalked it up to some obscure biological or behavioral speciation barrier.

DNA twists the plot

Ironically, one type of DNA evidence helped put the out-of-Africa model on top but later DNA evidence helped knock it back down. If brief, when Svante Pääbo and other researchers began the painstaking work of recovering nuclear DNA from Neandertal bones and sequencing it, they discovered that on average about 4 percent of living people’s genes are derived from Neandertals. (The telling exception was in people of modern African descent, whose genes were generally less than 1 percent Neandertal, which is what one might expect if the mixing would have occurred primarily outside Africa.)

Four percent might not sound like much, but it is substantially more than an out-of-Africa scenario with strict replacement rather than interbreeding would seem to allow. It’s remotely possible that this mixture is an artifact of old, unequal mixing of what became Neandertal genes within the ancestral African population (although anthropologist John Hawks has explained on his blog why that situation seems unlikely). The more likely explanation, though, is that some level of interbreeding did occur. For that reason, Stringer and other defenders of the concept now refer to a modified “mostly out of Africa” model that acknowledges some interbreeding but considers it largely trivial in extent and consequences.

That same evidence has, of course, only reinvigorated the multiregional hypothesis (though one might wonder why the percentage of ancient humans’ genes in us isn’t then higher). It has also nourished a popular new “assimilationist” school of thought that pragmatically splits the difference between multiregionalism and out-of-Africanism. The assimilationist model says that when the anatomically modern humans left Africa 80,000 years ago, they retained their own identity but also mixed to a degree with the older human populations they encountered. Both the modern and ancient groups became locally varying patchworks of physical traits and technologies. In the end, the ancients’ societies were too disrupted to survive but some of their genes persist in us.

The question of when and how humans emerged over the past few hundred thousand years is therefore considerably more complicated and less settled than it might have seemed a couple of decades ago. The same can be said for the closely related question about whether Neandertals, for example, represent their own species (Homo neanderthalensis) or just a subspecies (Homo sapiens neanderthalensis) alongside our own (Homo sapiens sapiens) – or whether, as Wolpoff would have it, virtually all of Homo has been one big species that has varied overtime.

Why we should care

Even if the science of human origins is still a work in progress, the accumulating information about how we got here and indeed what constitutes a member of the human race offers some useful perspectives on matters of scientific and ethical importance.

Perspective on the age of humanity. One small point that studies of the DNA of Neandertals and other ancient people illuminate is just how old or young we humans are as a species. The paleontological record indicates that the mean survival time for a mammalian species is about a million years, though some have lasted ten times that long. If we emerged only within the past 100,000 years or less, then Homo sapiens is indeed an amazingly young and precocious lot. And a loose, handwaving argument might therefore be made that we also probably have a commensurately long future ahead of us.

On the other hand, if Wolpoff is right and we are part of a species that has been around for two million years, then we are much more senior. It might make us look at the extinction rates with a little more sense of urgency.

Perspective on our nonprogressive evolution. The molecular study of our evolution also helps to drive home how unexceptional our biological history has been. Many icons of human evolution unintentionally reinforce a misleading sense of progress — witness the classic March of Progress illustration by Rudolph Zallinger that shows a modern human leading a Neanderthal and other “less evolved” ancestors.

But that sense really changes if we and Neandertals are seen as sibling groups, diverging but also sometimes re-merging throughout history. Our evolutionary history looks much less progressive and more like that of other species.

Perspective on race. For centuries (at least), arguments over race have invoked inappropriate biological concepts to make or defend distinctions among peoples — and distinctions in how they should be treated. They have likened races to subspecies to justify their inherent biological reality, along with some allegedly biological superiority, inferiority, or “otherness.”

A simple refutation of that idea has been the proof that the diversity of genetic characteristics within racial groups is greater than the diversity separating them: human races are not well enough defined and different enough to be meaningful biological groups. For that reason, many scientists now argue that race is not a biological concept but rather a social concept that sometimes carries biomedical consequences.

(Here’s what that means, if it isn’t immediately clear: In a society that mistreats the dark-skinned in general, for instance, black people may be at higher risk for diseases of poverty without having an intrinsic susceptibility to them. But an example that is perhaps less obvious is that of sickle-cell anemia, which is more common in those of black African descent than in those of white European descent. That’s because many people whose ancestors lived in regions where malaria was prevalent carry mutations for sickle-cell anemia that offer some protection from the parasite. But not all of those people are racially black and not all blacks carry the mutation. Sickle-cell information campaigns target predominantly black populations because society doesn’t accurately group people in terms of “ones whose ancestors had a lot of malaria.” In this case, race is a flawed but useful proxy for that nonexistent classification — but not because of the biological characteristics of the race as such.)

The foregoing is all true only in terms of race as we understand the concept today, however. If the multiregionalists and the assimilationists are right, then the Neandertals, Denisovans, and other ancient people we displaced may not have been separate species of person at all. They may instead have been races so different from modern humanity that they really were akin to other subspecies. Differences in their anatomical, genetic, behavioral, and intellectual traits would surely dwarf any seen in the world today among Homo sapiens. Color me naïve, but I would like to think that these insights might help to strengthen the spirit of color-blind brotherhood we ought to feel for one another.

(And in anticipation of a query I can feel coming: no, hypothetically, I would not be in favor of summarily treating Neandertals as second-class citizens if ever we could use technology to clone one. Neandertals were people and therefore, in my opinion, would deserve to be fully enfranchised. However, the question shows how ethically fraught such high-tech resurrections could be.)

Perspective on neurodiversity. In the course of their recent analysis of the Denisovan DNA, Meyer and Pääbo identified 23 highly conserved areas of the human genome that seem to be unique to our kind. Eight of those contain genes that previous studies have tied to nerve growth and other aspects of brain function. And three of the conserved genes — ADSL, CBTNAP2, and CNTNAP2 — have been implicated in some forms of autism.

Those correlations are not entirely surprising. Looking at the artwork and artifacts left by Neandertals, some archaeologists have argued that they seemed to lack a capacity for symbolic thought. Others such as John J. Shea disagree and suggest that the differences between modern and ancient thinking may have been exaggerated. Nevertheless, whatever evolutionary changes marked the emergence of modern humans, it’s likely they involved at least some important changes to our cognitive, linguistic, and social abilities. One might expect to find genes for those traits to be altered or absent in older types of humans.

I want to be perfectly clear on this point: this discovery absolutely does not mean that the Denisovans, Neandertals, and other ancients were autistic. Nor does it mean that autistic people exhibit prehistoric thinking. Rather, what it underscores is that normal modes of human thought occupy a broad continuum.

The “neurotypical” way in which most people see the world today is only one way of doing it. As enlightened studies of autism repeatedly drive home, we need to appreciate those variations as part of our human spectrum rather than just labeling them defective or abnormal.

With or without all our cognitive abilities, the Neandertals and Denisovans survived under amazingly hostile conditions for hundreds of thousands of years. Their different ways of thinking may have been dominant throughout long stretches of the past, and might even have had advantages over our own under their circumstances. The lesson that these ancients offer is that we should broaden our minds about how broad minds can be.

Source: Smart Planet

 

Genome Brings Ancient Girl to Life

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In a stunning technical feat, an international team of scientists has sequenced the genome of an archaic Siberian girl 31 times over, using a new method that amplifies single strands of DNA. The sequencing is so complete that researchers have as sharp a picture of this ancient genome as they would of a living person’s, revealing, for example that the girl had brown eyes, hair, and skin. “No one thought we would have an archaic human genome of such quality,” says Matthias Meyer, a postdoc at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. “Everyone was shocked by the counts. That includes me.”

That precision allows the team to compare the nuclear genome of this girl, who lived in Siberia’s Denisova Cave more than 50,000 years ago, directly to the genomes of living people, producing a “near-complete” catalog of the small number of genetic changes that make us different from the Denisovans, who were close relatives of Neandertals. “This is the genetic recipe for being a modern human,” says team leader Svante Pääbo, a paleogeneticist at the institute.

Ironically, this high-resolution genome means that the Denisovans, who are represented in the fossil record by only one tiny finger bone and two teeth, are much better known genetically than any other ancient human—including Neandertals, of which there are hundreds of specimens. The team confirms that the Denisovans interbred with the ancestors of some living humans and found that Denisovans had little genetic diversity, suggesting that their small population waned further as populations of modern humans expanded. “Meyer and the consortium have set up the field of ancient DNA to be revolutionized—again,” says Beth Shapiro, an evolutionary biologist at the University of California, Santa Cruz, who was not part of the team. Evolutionary geneticist Sarah Tishkoff of the University of Pennsylvania agrees: “It’s really going to move the field forward.”

Pääbo’s group first gave the field a jolt in May 2010 by reporting a low-coverage sequence (1.3 copies on average) of the composite nuclear genome from three Neandertals. They found that 1% to 4% of the DNA of Europeans and Asians, but not of Africans, was shared with Neandertals and concluded that modern humans interbred with Neandertals at low levels.

Just 7 months later, the same group published 1.9 copies on average of a nuclear genome from a girl’s pinky finger bone from Denisova Cave. They found she was neither a Neandertal nor a modern human—although bones of both species had been found in the cave—but a new lineage that they called Denisovan. The team found “Denisovan DNA” in some island Southeast Asians and concluded that their ancestors also interbred with the ancestors of Denisovans, probably in Asia.

But these genomes were too low quality to produce a reliable catalog of differences. Part of the problem was that ancient DNA is fragmentary, and most of it breaks down into single strands after it is extracted from bone.

Meyer’s breakthrough came in developing a method to start the sequencing process with single strands of DNA instead of double strands, as is usually done. By binding special molecules to the ends of a single strand, the ancient DNA was held in place while enzymes copied its sequence. The result was a sixfold to 22-fold increase in the amount of Denisovan DNA sequenced from a meager 10-milligram sample from the girl’s finger. The team was able to cover 99.9% of the mappable nucleotide positions in the genome at least once, and more than 92% of the sites at least 20 times, which is considered a benchmark for identifying sites reliably. About half of the 31 copies came from the girl’s mother and half from her father, producing a genome “of equivalent quality to a recent human genome,” says paleoanthropologist John Hawks of the University of Wisconsin, Madison, who was not part of the team.

Now, the view of the ancient genome is so clear that Meyer and his colleagues were able to detect for the first time that Denisovans, like modern humans, had 23 pairs of chromosomes, rather than 24 pairs, as in chimpanzees. By aligning the Denisovan genome with that of the reference human genome and counting mutations, the team calculated that the Denisovan and modern human populations finally split between 170,000 and 700,000 years ago.

The researchers also estimated ancient Denisovan population sizes by using methods to estimate the age of various gene lineages and the amount of difference between the chromosomes the girl inherited from her mother and father. They found that Denisovan genetic diversity, already low, shrank even more 400,000 years ago, reflecting small populations at that time. By contrast, our ancestors’ population apparently doubled before their exodus from Africa.

The team also counted the differences between Denisovans and chimps, and found that they have fewer differences than do modern people and chimps. The girl’s lineage had less time to accumulate mutations, and the “missing evolution” suggests she died about 80,000 years ago, although the date is tentative, says co-author David Reich, a population geneticist at Harvard University. If this date—the first proof that a fossil can be directly dated from its genome—holds up, it is considerably older than the very rough dates of 30,000 to more than 50,000 years for the layer of sediment where the fossils of Denisovans, Neandertals, and modern humans all were found.

The team says the new genome confirms their previous findings, showing that about 3% of the genomes of living people in Papua New Guinea come from Denisovans, while the Han and Dai on mainland China have only a trace of Denisovan DNA. Furthermore, the team determined that Papuans have more Denisovan DNA on their autosomes, inherited equally often from both parents, than on their X chromosomes, inherited twice as often from the mother. This curious pattern suggests several possible scenarios, including that male Denisovans interbred with female modern humans, or that these unions were genetically incompatible, with natural selection weeding out some of the X chromosomes, Reich says.

The new genome also suggests one odd result. By using the detailed Denisovan genome to sharpen the view of their close cousins the Neandertals, the team concludes that living East Asians have more Neandertal DNA than Europeans have. But most Neandertal fossils are from Europe; paleoanthropologist Richard Klein of Stanford University in Palo Alto, California, calls the result “peculiar.”

Most exciting to Pääbo is the “nearly complete catalog” of differences in genes between the groups. This includes 111,812 single nucleotides that changed in modern humans in the past 100,000 years or so. Of those, eight were in genes associated with the wiring of the nervous system, including those involved in the growth of axons and dendrites and a gene implicated in autism. Pääbo is intrigued in particular by a change in a gene that is regulated by the so-called FOXP2 gene, implicated in speech disorders. It is “tempting to speculate that crucial aspects of synaptic transmission may have changed in modern humans,” the team wrote. Thirty-four genes are associated with disease in humans. The list suggests some obvious candidates for gene-expression studies. “The cool thing is that it isn’t an astronomically large list,” Pääbo says. “Our group and others will probably be able to analyze most of them in the next decade or two.”

Back in Leipzig, the mood is upbeat, as researchers pull fossil samples off the shelf to test anew with “Matthias’s method.” First on Pääbo’s list: Neandertal bone samples, to try to produce a Neandertal genome to rival that of the little Denisovan girl.

Source: Scientific American.