NEWS | I N D E P T H
HUMAN EVOLUTION
Neandertal genes linked to modern diseases
DNA inherited from our extinct cousins boosts risk of depression and other disorders
By Ann Gibbons
D
epressed? Your inner Neandertal may
be to blame. Modern humans met
and mated with these archaic peo-
ple in Europe or Asia about 50,000
years ago, and researchers have long
suspected that genes picked up in
these trysts might be shaping health and
well-being today. Now, a study on p. 737 de-
tails their impact. It uses a powerful new
method for scanning the electronic health
records of 28,000 Americans to show that
some Neandertal gene variants today can
raise the risk of depression, skin lesions,
blood clots, and other disorders.
Neandertal genes aren’t all bad. “These
variants sometimes protect against a dis-
ease, sometimes make people more sus-
ceptible to disease,” says paleogeneticist
Svante Pääbo of the Max Planck Institute
for Evolutionary Anthropology in Leipzig,
Germany. Two other new studies identified
three archaic genes that boost
immune response. And most
archaic genes that persist in Neandertals’ hidden legacy
humans were likely beneficial
In many people today, genes inherited from Neandertals affect systems all over the
in prehistoric times. But some body, raising the risk of certain diseases. But some Neandertal genes have benefi-
now cause disease because cial effects, for example boosting the immune system.
modern lifestyles and environ-
ments are so diferent.
Living people carry only Brain
trace amounts of Neandertal Depression;
DNA, which makes its impact addiction to
on health more striking. “The tobacco
Neandertal genetic contribu-
tion to present-day people Lymph nodes
immune boost
seems to have larger physiologi-
cal efects than I would have
naïvely thought,” says Pääbo,
who helped launch this avenue
of research by sequencing the
first ancient genomes but was
not involved in these studies.
On average, Europeans and
Asians have inherited about
1.5% of their genomes from Ne-
andertals. Island Melanesians
Skin
carry an additional 2% to 3%
Precancerous
of DNA inherited from another skin lesions
extinct group, the Denisovans.
Most Africans lack this archaic
DNA because the interbreeding
happened after modern hu-
mans left Africa.
By comparing the genomes of
a few Neandertals and one Den-
648 12 FEBRUARY 2016 • VOL 351 ISSUE 6274
isovan with people in the 1000 Genomes
database, computational biologists have re-
cently uncovered about 12,000 Neandertal
gene versions, or haplotypes, in living Eu-
ropeans and Asians (Science, 28 February
2014, p. 1017). Researchers had clues to the
function of a handful of these haplotypes—
some were thought to be involved in the im-
mune system, or the development of skin
or hair, for example. But nailing down their
precise function has required costly gene
expression studies in tissue or animal mod-
els (Science, 3 July 2015, p. 21).
A breakthrough came when population
geneticist Joshua Akey of the University of
Washington, Seattle, and evolutionary gen-
omicist Tony Capra of Vanderbilt University
in Nashville independently realized that
they could fish for Neandertal gene vari-
ants in a medical database, the Electronic
Medical Records and Genomics (eMERGE)
Network. This consortium in nine U.S. cit-
ies links patients’ genetic data with their
Heart/Blood
Hypercoagulation
Stomach
Malnutrition
Kidneys
and urethra
Urinary tract
disorders
Published by AAAS
medical data, in the form of specific billing
codes that record diagnoses for illnesses
and other conditions. Thus eMERGE allows
researchers to track correlations between
genes and symptoms in tens of thousands
of people.
Akey and Capra joined forces and
searched for more than 6000 Neander-
tal haplotypes in genetic data from 28,416
adults of European ancestry. After pinpoint-
ing chunks of DNA inherited from Nean-
dertals, the team used statistical analysis to
link possession of these archaic variants to
a higher risk of the diseases or other traits
captured in the billing data, Capra says.
The search netted a dozen Neandertal
genes likely to cause significant risk of dis-
ease today. For example, one gene variant
apparently makes blood more sticky and
prone to coagulate. This fast clotting may
have spelled the diference between life and
death when Neandertals hunted danger-
ous animals or hemorrhaged after birthing
big-brained babies. But it can
also increase the risk of blood
clots and strokes, which would
have been much less common
in prehistoric times when most
people died young.
The researchers also found
a number of Neandertal genes
associated with neurological
conditions, including depres-
sion, which can be triggered by
disturbed circadian rhythms.
Other variants were linked
to precancerous skin lesions
called actinic keratoses. Capra
speculates that Neandertal
brain chemistry and their skin
DIAGRAM: ADAPTED FROM DEBORAH BREWINGTON/VANDERBILT UNIVERSITY
responses to sunlight may both
have been attuned to the light
conditions and lifestyles of
prehistoric Europe. The gene
variants responsible may be
maladaptive now that most
people live by artificial light.
Other Neandertal alleles reg-
ulate the transport of thiamine,
or vitamin B1, which metabo-
lizes carbohydrates in cells of
the gut. Neandertal diets, rich
in meat and nuts, may have pro-
vided ample thiamine, but peo-
ple munching processed foods
today may not get enough, and
having the Neandertal vari-
sciencemag.org SCIENCE
 ant may predispose them to malnutrition,
Capra speculates.
The study also revealed Neandertal genes
associated with incontinence, bladder pain,
and urinary tract disorders. And a single
base change was associated with nicotine
addiction, making it the second Neandertal
allele found so far to boost the risk of to-
bacco addiction.
The Neandertal health legacy isn’t en-
tirely negative. Two studies published in
The American Journal of Human Genetics
last month identified three archaic genes
that boost the innate immune response,
which helps defend against fungi and par-
asites as well as bacteria. All three have
been strongly selected for in Europeans
and Asians, says computational biologist
Janet Kelso of Max Planck, lead author of
one study. The three genes work together
in subtle ways to regulate the expression of
toll-like receptors on the surface of white
blood cells, presumably boosting the in-
nate response, says Lluis Quintana-Murci,
a population geneticist at the Pasteur In-
stitute and the French National Center for
Scientific Research in Paris, lead author of
the other study.
Such examples suggest that as modern
humans entered new environments that
harbored new pathogens, they took an
evolutionary shortcut by picking up ben-
eficial genes from other hominins (Science,
24 July 2015, p. 362). “You just borrow di-
versity from another species or population
that had lived there longer,” Quintana-Murci
says. Neandertals had at least 200,000 years
to adapt to life in the Middle East and Eu-
rope before moderns got there.
But however beneficial in the Pleistocene
and to people living in poor conditions to-
day, even immune-boosting genes may have
deleterious efects in the United States and
Europe, where people face fewer parasites:
Kelso found that the archaic receptor genes
were strongly linked to allergies. “The price
to pay today is that when you boost the
immune response, it can be bad for us in
terms of autoimmunity, inflammation, and
allergies,” Quintana-Murci says.
Exactly how these genes afected Ne-
andertals themselves is not always clear.
“This doesn’t mean that Neandertals were
depressed,” or had more skin cancer, cau-
tions computational geneticist Sriram
Sankararaman of the University of Califor-
nia, Los Angeles.
These studies are just the beginning, as
researchers search for more Neandertal
variants passed on in those ancient encoun-
ters, and broaden their databases of mod-
DATA: CSIRO
ern genomes to the hundreds of thousands.
“We suspect there are many more Neander-
tal alleles floating out there,” Capra says. ■
SCIENCE sciencemag.org
AUSTRALIA
Research chief cuts climate
studies, sets new priorities
CSIRO to trim staff as it seeks closer alignment with industry
By Leigh Dayton, in Sydney, Australia
A
ustralia’s premier research agency
has long been at the vanguard of cli-
mate science. “Our climate models are
among the best in the world and our
measurements honed those models to
prove global climate change,” Larry
Marshall, chief executive of the Common-
wealth Scientific and Industrial Research Or-
ganisation (CSIRO) in Canberra, gushed in
an email to his staf last week. But Marshall
says that job is finished now, and it’s time for
his organization to move on.
For scores of climate scientists at CSIRO,
Marshall’s email amounts to a eulogy. To “re-
align and restore our business for growth,”
the former Silicon Valley, California, venture
capitalist stated that up to 350 jobs could
be eliminated over the next
2 years, including 110 posi-
tions in the Oceans and Atmo-
sphere division, the bulwark of
CSIRO’s climate research. The
job losses, Marshall wrote, are
5200
Total CSIRO positions
“something that we must do to
renew our business.”
Outsiders warn that the cuts
will gut CSIRO’s vaunted work
on climate science in the South-
ern Hemisphere. “I am stunned
350
Job losses over
the next 2 years
by reports that CSIRO manage-
ment no longer thinks measur-
ing and understanding climate
change is important, innova-
tive, or impactful,” says former
Australian chief scientist Penny
Sackett, now at the Australian
110
Climate researchers
will be let go
National University in Can-
berra. “This is a flawed strat-
egy,” adds John Church, who leads CSIRO’s
Sea Level Rise program, which he says is
on the chopping block. The cuts, he argues,
will prevent Australia from gathering data
necessary to meet its obligations under the
2015 climate accord to slash greenhouse gas
emissions by 26% to 28% from 2005 levels
by 2030.
In his email, Marshall cited a number of
priorities that he would like to boost instead,
to more closely align CSIRO with industry.
For instance, he espouses research to make
titanium ink for 3D printing from Australia’s
mineral sands, produce cleaner diesel fuel
Published by AAAS
from coal, and breed “new strains of food
and agricultural products that are healthier,
more sustainable and highly diferentiated.”
Marshall is confident that CSIRO scientists
will get with the program: “Our people are
innovative and many can reinvent them-
selves to learn these new areas,” he wrote.
CSIRO’s realignment comes on the heels of
more than $15 million in cuts to climate and
environmental science in the 2014–15 fed-
eral budget. In light of both developments,
Andrew Holmes, president of the Australian
Academy of Science in Canberra, urges the
government “to quickly make alternative
arrangements” to continue a national pro-
gram of climate research.
Marshall did not respond to requests
for comment. But in an 8 February state-
ment posted to CSIRO’s website, he stated
that the cuts will not afect the
Cape Grim air pollution moni-
toring station, jointly man-
aged by CSIRO and the Bureau
of Meteorology, which is the
source of much of Australia’s
greenhouse gas data. Other cli-
mate science assets, including
CSIRO’s Investigator research
vessel, will be protected, he
noted. Fears that CSIRO is turn-
ing its back on climate research
are misplaced, a spokesperson
for science minister Christopher
Pyne told Science. “CSIRO will
continue to invest heavily in cli-
mate research,” he said.
Much of the angst appears
to be a reaction to Marshall’s
management style. “Turnover
is essential for a healthy busi-
ness,” he wrote in his email. Marshall’s use
of phrases such as “reductions in headcount,”
“renew our business,” and “business units,”
says Ian Lowe, an expert in science and soci-
ety with Gri!th University, Brisbane, in Aus-
tralia, “reveals that the government is trying
to sabotage our public science body and turn
it into a consulting business.” Nadine Flood,
national secretary of the union in Haymarket
that represents CSIRO employees, charges
that Marshall is modeling CSIRO on Net-
flix and Silicon Valley. “IT startups might be
agile,” she says, “but deep science cannot be
simply switched on and of again.” ■
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