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Archaeologists David Anthony and
Dorcas Brown measure a skeleton from
the Russian steppe whose 5000-year-old
DNA revealed close ties with Europeans.

REVOLUTION As it smashes disciplinary boundaries, ancient DNA

IN HUMAN
EVOLUTION
is rewriting much of human prehistory
By Ann Gibbons

A
t 6:30 p.m. on a blustery March pared equipment for the next day’s round ing a single fossil’s genome—and making
evening in Boston, most of the of sequencing. sure the result was not muddied by contam-
researchers on the second floor Next door, postdocs from three countries ination with modern DNA—was a titanic
of Harvard Medical School’s sat at their large computer screens, trying to effort. Now, thanks to technological break-
New Research Building were at figure out how to analyze sequences faster. throughs that have vastly accelerated se-
a beer hour, but David Reich’s “Exactly a year ago, we had DNA from one quencing and made the results more trust-
lab was still bustling. Molecu- farmer from Germany, one farmer from worthy, DNA researchers the world over are
lar biologist Nadin Rohland was Luxembourg, and two or three hunter- awash in data (see p. 359). The result is a
working late, trying to finish se- gatherers,” said Iosif Lazaridis from Greece. series of revelations about humanity’s past.
PHOTO: © DREW GURIAN

quencing 390,000 bases of DNA from each “Suddenly we had 50. Now it’s in the 100s—I Ancient DNA has led to the discovery of
of 92 Bronze Age human bones. The sam- don’t know if we’ve crossed the thousands.” new types of ancient humans and revealed
ples had been streaming in from archae- Pontus Skoglund, from Sweden, joked: interbreeding between our ancestors and
ologists, and she was hustling to keep up. “There’s too much data!” our archaic cousins, which left a genetic
“We’re really busy,” Rohland said as she pre- Just 5 years ago, extracting and decipher- legacy that shapes our health and appear-

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ance today. And because investigators can times aroused suspicion. Some researchers of contamination—Stringer, for one, had
now sequence entire ancient populations, at first refused access to fossils, and the left a trail of his own DNA on fossils across
as Reich’s lab is doing, ancient DNA is add- Czech police searched his belongings, saying Europe. But Pääbo and his colleagues ulti-
ing layers of complexity to the story of how that his visit was of “no value to the people mately managed to create a composite ge-
ancient populations migrated and mixed of Czechoslovakia.” In Rome, thieves stole nome from three female Neandertals and
across the globe. “The whole field is explod- the modern human skull. compare it with modern human DNA. The
ing in terms of its impact,” says Christina But Stringer persevered, carefully mea- team found that Neandertals did indeed
Warinner of the University of Oklahoma, suring the rare bones. He noted that have a genome distinct from our own—but
Norman. “The data that’s coming out is Neandertals had long, low skulls with that living Europeans and Asians had inher-
completely rewriting what we know about pronounced brow ridges and projecting ited 1% to 3% of their DNA from Neander-
human prehistory.” midfaces, whereas the younger modern hu- tals (Science, 7 May 2010, p. 680).
The findings are forcing a shotgun mar- mans had globular skulls and flat faces. He That genetic legacy meant that Stringer’s
riage between ancient DNA spe- view of the fossils was incom-
cialists and other researchers plete: Neandertals had interbred
trying to unravel the past, in- with modern humans at least
cluding anthropologists, archae- once. More recent ancient DNA
ologists, and population geneti- analyses suggest that such inter-
cists. For them, the technique breeding happened at least three
poses unsettling challenges as times, probably 37,000 to 85,000
well as opportunities. Ancient years ago in the Middle East and
DNA has contradicted prevail- Europe (Science, 22 May, p. 847).
ing views—that the invention One modern human who lived
of farming reflected the spread in Romania roughly 40,000
of ideas rather than people, for years ago even had a great-
example. But it is also enabling great-great-grandparent who
these scientists to answer ques- was a Neandertal, Pääbo’s team
tions they could not previously reported in June.
address, and many are now The same year Pääbo’s team
seeking collaborations with an- published the Neandertal ge-
cient DNA researchers. “Before nome, it sequenced a sliver of a
2010 I didn’t know anything fossil pinky bone from Denisova
about DNA,” says archaeologist Cave in Siberia and found ge-
David Anthony of Hartwick netic evidence of a new kind of
College in Oneonta, New York, human, related but not identical
who provided bone samples of to Neandertals. The team called
ancient herders from Russia to them Denisovans and found
Reich’s lab. “I’ve had to ramp up that they, too, had mixed with
my knowledge—ancient DNA is modern humans so that Mela-
becoming a tool for archaeology nesians carry up to 5% Deniso-
almost like radiocarbon dating.” van DNA (Science, 26 August
Such collaborations aren’t 2011, p. 1084).
always easy. Despite their inter- Although ancient DNA proved
est, archaeologists, for example, Stringer wrong about inter-
are still outsiders to the world Excavations of a Bronze Age settlement in Russia’s Samara Valley unearthed breeding among our ancestors,
of DNA, says archaeogeneticist dozens of skeletons, including an adult male (above). Their DNA is helping reveal he embraces the new results. As
Johannes Krause of the Max the origins of Europeans and Asians. anthropologist Marcia Ponce de
Planck Institute for the Sci- León of the University of Zurich
ence of Human History in Jena, Germany. concluded that Neandertals in Europe were in Switzerland puts it, “ancient DNA answers
“Archaeologists can’t analyze that kind of not the ancestors of modern humans there, questions that morphology alone cannot an-
data,” he says. “And they aren’t completely in as was then widely believed, but a separate swer conclusively—and raises questions that
charge anymore.” But they can’t ignore the species that had been completely replaced have never been asked before.”
burgeoning new field. “The new data can re- by modern humans. That put him at odds Ponce de León, who specializes in state-
write history.” with researchers who focused on different of-the-art morphological analyses, notes
anatomical traits and thought that Nean- that that lesson emerged yet again earlier
WHEN PALEOANTHROPOLOGIST Chris dertals had interbred with our ancestors, this year, when she and others reanalyzed
Stringer was a 22-year-old grad student in and even were members of our own species, the skull and sequenced the genome of
the early 1970s, he took his calipers to mu- Homo sapiens. Kennewick Man, an 8500-year-old skeleton
PHOTOS: © DAVID W. ANTHONY (2)

seums around Europe, applying a new, sys- The infighting went on for years. Mean- found on the shore of the Columbia River
tematic measurement procedure to all the while, paleogeneticist Svante Pääbo of the in Washington state. Some scientists had
skulls of Neandertals and modern humans Max Planck Institute for Evolutionary An- argued that Kennewick’s long, low skull re-
he could get his hands on. Traveling in a bat- thropology in Leipzig, Germany, took a dif- sembled those of Polynesians or the Ainu
tered Morris Minor, with long hair, barely ferent, risky route to answering the ques- people of Japan rather than the broader,
enough cash to stay in youth hostels, and a tion: He studied DNA from Neandertal fos- rounder skulls of today’s Native Americans.
modern human skull as passenger, he some- sils. First, he had to overcome the problems They suggested that Kennewick Man might

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 diabetes, that apparently had been
shaped by natural selection. “I re-
member thinking how cool it was to
be able to use patterns of variation
in contemporary individuals to learn
about what influenced our ancestors’
ability to survive and reproduce,”
says Akey, now at the University of
Washington, Seattle.
He recalls, though, that “all the
data could fit in an Excel spread-
sheet.” That’s because living people
preserve only a fraction of the ge-
netic diversity of ancient ones. “Pop-
ulation geneticists were trapped in
time—they could only look at what
was here today,” Skoglund says. Now
he, Akey, and others can look deep
into the past by analyzing the ge-
netic makeup of people who lived
long ago. “It seems like science fic-
tion to be able to generate large
amounts of sequence data from in-
dividuals who lived 30,000, 40,000,
50,000 years ago,” Akey says.
As soon as these investigators
post sequences from ancient people
into public databases, the data feed
whole schools of evolutionary re-
searchers downstream, who fish for
signs of evolution and adaptation in
our genomes. Population geneticists
who have never measured a fossil
and computational biologists who
have never worked in a clean room
now sit at their computers unravel-
ing the complex genetics of what
made us modern.
Svante Pääbo has transformed views Today, Akey continues to seek
of human evolution by sequencing genes that were favored or weeded
the genomes of archaic humans. out by natural selection. But now
he’s on the alert for something that
hadn’t been on his radar before:
have been part of an early wave of migra- All the same, Stringer cautions, “it’s not genes that our ancestors lifted from archaic
tion to the Americas and only distantly time to throw away the artifacts and fos- humans. Adaptation is usually a slow pro-
related to today’s Native Americans; their sils.” They yield insight into ancient peo- cess, as beneficial mutations often require
anatomical research influenced court deci- ple’s activities that genes just can’t provide. hundreds or thousands of generations to
sions preventing the reburial of the bones “No amount of ancient DNA would tell us spread through a population. But the Nean-
according to Native American customs. whether the Neandertals buried their dead, dertal and Denisovan genomes have shown
Ponce de León and others confirmed the or whether the ancestors of Australasians that in some cases our modern human an-
anatomical differences seen in Kennewick used boats to reach New Guinea and Aus- cestors were able to take an evolutionary
Man’s skull. But in the same study, evolu- tralia,” he says. shortcut: As they spread around the globe,
tionary biologist Eske Willerslev of the Uni- they met other kinds of humans who were
versity of Copenhagen and others found that WHEN POPULATION GENETICIST Joshua already adapted to the local environment.
Kennewick Man’s genome shows that he was Akey was a graduate student in the 1990s, By breeding with them, our ancestors were
closely related to Native Americans, includ- his fieldwork involved sitting in front of able to snag beneficial genes.
ing at least one of the five tribes that origi- a computer and downloading data on the “We’re figuring out how interactions with
PHOTO: © ROB CLARK/INSTITUTE

nally fought to rebury him. “Ancient DNA genes of living people. He was scanning for Neandertals and Denisovans helped our an-
analyses provide thousands of independent, genes that had been targets of natural se- cestors survive,” Akey says. Such “adaptive
often neutrally evolving, features per indi- lection, and he succeeded: He and his col- introgression” has been well documented
vidual,” Ponce de León says. “In morphology, leagues analyzed variation in the genomes of in plants and bacteria. Its importance in
we typically have comparatively few fea- the 270 people collected by the International human evolution was highlighted last year,
tures, which are highly interdependent and HapMap Project and spotted 174 genes, in- when researchers discovered that Tibetan
only partially reflect the genome.” cluding two linked to cystic fibrosis and highlanders had inherited a “superathlete”

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gene variant called EPAS1 from Denisovans. been beneficial: The DNA record shows that Not all such archaic genes are beneficial:
This ancient variant, which helps Tibet- these genes spread rapidly through Europe- Mayas in Mexico, some Native Americans,
ans use oxygen more efficiently, was found ans and Asians. and about 25% of Asians retain an allele
in Denisovans but not in Neandertals or Neandertals, whose ancestors had at least from Neandertals that boosts their risk for
other people around the world, according 200,000 years to adapt to Europe’s gray skies diabetes. The gene variant plays a role in the
to work by population ge- and frigid winters, also be- breakdown of fats and may have been benefi-
neticist Rasmus Nielsen of queathed some skin genes to cial when diets were lean and our ancestors
the University of California the modern humans they en- needed to store fat efficiently. Also, several
(UC), Berkeley, and his Chi- countered, including a gene independent studies have noted that long
nese collaborators. called BNC2, which is associ- stretches of the modern genome are archaic
Other archaic genes helped ated with light skin in Europe- “deserts” lacking any Neandertal or Deniso-
our ancestors resist disease. ans and allows skin to synthe- van signal. Researchers suspect that natural
“When modern humans size more vitamin D. (Many of selection weeded out deleterious archaic
started dispersing around today’s Africans, whose ances- genes in these regions, and the DNA here
the globe, they encountered tors didn’t mingle with Ne- may be what distinguishes us from those ar-
unique pathogens that ar- andertals, do not carry these chaic people. “This has the potential to con-
chaic humans were better A sliver of pinky bone from gene variants.) Akey’s team tribute to our understanding of what makes
adapted to,” Akey says. Luck- Denisova Cave generated a also found that Neandertals modern humans modern,” Akey says.
ily for modern humans, they high-quality genome. contributed other genes that To date, Pääbo has assembled a catalog
picked up some immune protect skin against abrasion of about 31,000 base-pair changes, or single
genes from Neandertals, such as a version or water loss (Science, 28 February 2014, p. nucleotide polymorphisms (SNPs), in which
of STAT2, a gene involved in the interferon 1017). These chunks of archaic DNA have modern humans carry a different version
response that fights viral infections; mod- provided “a rich reservoir” of genes that have from Neandertals and Denisovans. Several
erns also acquired different types of human allowed Europeans and Asians (including teams are doing lab work in stem cells and
leukocyte antigen genes, which help the the ancestors of Native Americans) to adapt mice to try to figure out what some of these
immune system detect foreign invaders. Re- rapidly to various environmental conditions, genes do (Science, 3 July 2015, p. 21).
searchers are now trying to figure out just according to a June report in Nature Reviews The revolution in ancient studies has
how these archaic gene variants change Genetics by Nielsen and Fernando Racimo of brought Akey full circle—back to scanning
immune function, but the effect must have UC Berkeley. data from living humans: He is now col-

The most wanted genomes

Genomes from ancient humans in these artists’ reconstructions could reveal much about our evolution but remain just out of reach—for now
CREDITS: (PHOTO) © ROB CLARK/INSTITUTE; (IMAGES) © JOHN GURCHE (3)

Homo floresiensis, aka “the hobbit” Homo heidelbergensis Homo erectus

Found in Liang Bua cave on the Indonesian island In the 1990s, archaeologists found the remains of This iconic human ancestor, the frst with a notably
of Flores in 1998, this hominin was just over 1 about 32 archaic people with large brows and short, enlarged brain, lived 1.8 million to 1 million years
meter tall but has sparked an outsize controversy. compact bodies in a cave in northern Spain. Many ago, so sequencing its DNA seems a bit like science
Many think the bones represent an amazingly tiny researchers thought that the 440,000-year-old fction. But researchers are eager to do so, because
species of ancient human, but a few researchers fossils were ancestral to the Neandertals. But in it is thought to be ancestral to later hominids,
say the hobbit, who lived as recently as 18,000 2013, researchers at the Max Planck Institute for including Neandertals, Denisovans, and modern
years ago, is a diseased member of our own Evolutionary Anthropology in Leipzig, Germany, humans. Comparing H. erectus with its descendants
species. DNA sequencing could put that argument managed to sequence the mitochondrial genome from could show what these three types of humans once
to rest, and reveal any kinship with other archaic a H. heidelbergensis legbone, and found it looked more had in common, how they have diverged, and the
humans. But independent eforts have so far like that of another ancient group, the Denisovans. stepwise changes that led to H. sapiens. To glimpse
failed to retrieve any genetic material from the Max Planck researchers are now trying to sequence H. erectus’s genome, researchers are now analyzing
hobbit bones. its nuclear genome to check this puzzling result. long stretches of very old DNA in its descendants.

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Who’s who of ancient genomes

Some of the best known nuclear genomes sequenced from Vindija Cave Neandertals Ust’-Ishim man
human ancestors across the Northern Hemisphere. 34,000 to 43,000 years old 45,000 years old
Croatia Siberia
Three Neandertal Oldest modern
women. Made up first human genome
Anzick boy Neandertal genome. sequenced.
12,700 years old Mal’ta boy
Montana 24,000 years old
Related to Native Siberia
Americans. Modern human,
related to Native
Americans.
Kennewick Man
8500 years old
Washington El SidrÓn Cave
Neandertals Denisova girl
Subject of court More than 50,000 years old
49,000 years old
battle. Related to Siberia
Spain
Native Americans.
Neandertal family Dark skin, brown hair, brown eyes.
group of 12 with Revealed the existence of a new
Peștera cu Oase kind of archaic human.
red hair, fair skin. Cave man
About 40,000 years old Denisova Cave Neandertal
Romania More than 50,000 years old
Modern man with Siberia
recent Neandertal Inbred Neandertal woman.
ancestor.

laborating with researchers worldwide to bones for DNA analysis, he agreed to let the that the genetic evidence was “unambigu-
see whether archaic versions of genes boost researchers grind up small samples of the ous,” they added cautionary notes and signed
the risk of schizophrenia, diabetes, and Yamnaya’s limb bones for sequencing. To onto the paper, Reich says.
autoimmune disorders. For better or worse, quickly probe their population history and DNA repeatedly shows that people who
“we’re all amalgamations of the past, with appearance, Reich’s team sequenced not live in a place today rarely are related to
little bits and pieces of DNA that originated the full genomes but a set of 390,000 key those who lived there thousands of years
all over the world and, in some cases, from SNPs from each of 69 ancient Europeans earlier. “People in every inhabited continent
different species,” Akey says. and Asians, including nine Yamnaya. The 10,000 years ago looked different to people
results, published in February, showed that in these same regions today,” Stringer says.
FOR ARCHAEOLOGIST ANTHONY, in con- the Yamnaya were the source of a massive For example, when Willerslev’s team se-
trast, ancient DNA is a tool for unveiling migration of herders who swept into the quenced the genome of a 24,000-year-old
ancient populations—in particular, a mys- heartland of Europe on horseback about Siberian boy from Mal’ta in 2013, it found
terious group of tall young herders he has 5000 years ago—and that most Europeans no genetic connection to anyone living
excavated from beneath earth mounds in can trace at least some of their ancestry to in Central Asia today. But the Mal’ta boy
the Samara Valley of Russia. He and Dorcas this group. Anthony got some of his ques- was related to Kennewick Man and Native
Brown, his wife and research partner, used tions answered: The Yamnaya had brown Americans, suggesting that he represented
all the tricks of their trade to probe how eyes, brown hair, and light skin. And the an ancient source population for migrations
these elite members of the Yamnaya herd- people in the elite graves were members of Paleoindians to the Americas.
ing culture lived and died about 5000 years of the same clan, showing that family ties Anthony hopes ancient DNA will help
ago. With their Russian collaborators, they influenced status. “One of the wonderful him continue to learn about the Yamnaya.
measured bones, analyzed isotopes, and ex- things about ancient DNA is that it gives Could these elite herders drink alcohol? Did
amined their grave goods. Finally, the pair these old samples new life,” he says. their dogs travel with them? To answer such
sealed bone fragments of the Yamnaya into Sometimes, though, the results can be questions, ancient DNA researchers need
plastic bags and stored them on a shelf. hard for archaeologists to handle. “When we data from many more archaeological sites.
But Anthony was haunted by all he still circulated the final version of our paper, the So at the last annual meeting of the Society
didn’t know about the nomads who moved European archaeologists who had given us for American Archaeology, Anthony could
across the northern steppe on horseback. samples were distressed,” Reich says. They be found recruiting samples for Reich’s lab.
“I wanted to know their eye color, skin were startled when the genetic data showed There are “samples lying all over Europe
color, hair color,” he says. “And were the the Yamnaya from the Russian steppes were and North America, in labs sitting in the
people buried in these elite graves related the ancestors of the Corded Ware people in dark,” he says.
MAP: M. ATAROD

to each other?” Germany, because it seemed to echo an erro- Most archaeologists, he says, are happy to
So when he got a phone call in 2013 from neous idea about Aryan culture propagated be asked. “People are excited that their sam-
a colleague of Reich’s who was seeking by the Nazis. But once archaeologists realized ples could be a source of ancient DNA.” ■

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