SCIENCE sciencemag.org 21 DECEMBER 2018 • VOL 362 ISSUE 6421 1347A fragment of bone from a woman who lived more than 50,000 years ago has revealed a
startling connection between two extinct groups of archaic humans. Ancient DNA extracted
from the bone, found in a cave in Siberia in 2012, showed the woman’s mother was
a Neanderthal and her father was a Denisovan, the mysterious group of ancient humans
whose remains were discovered in the same cave in 2011.
Researchers knew Denisovans, Neanderthals, and modern humans interbred, at least
occasionally, in ice age Europe and Asia. The genes of both types of archaic human are present
in Asian and European people today. And other fossils found in the Siberian cave have shown
members of all three groups lived there at different times. But the new finding is intimate
testimony of an encounter between a Denisovan and a Neanderthal.
After sequencing DNA from the bone, researchers at the Max Planck Institute for Evolution-
ary Anthropology in Leipzig, Germany, found it came from a female, and that her genome
matched those of Denisovans and Neanderthals in roughly equal measure. That could have been
because her parents themselves had mixed ancestry. But her chromosome pairs harbored differ-
ent variants—so-called heterozygous alleles—of nearly half her genes, suggesting the maternal
and paternal chromosomes came from different kinds of humans. Her mitochondrial DNA,
which is almost entirely inherited from the mother, was uniformly Neanderthal, so the research-
ers concluded she was a first generation hybrid of a Denisovan male and Neanderthal female.
A closer look at the genome suggested her father also had some Neanderthal ancestry.
In another telltale finding, the woman’s Neanderthal genes are closer to those of a Neander-
thal found in Croatia than to those of earlier Neanderthal inhabitants of the Denisova Cave.
That suggests, the authors say, that distinct groups of Neanderthals migrated back and forth be-
tween western Europe and Siberia multiple times. Along the way, apparently, they freely spread
their genes to outsiders. Why did Denisovans and Neanderthals remain genetically distinct?
Geographic barriers probably played a role, but researchers need more ancient DNA from
different sites to understand the true influence of these prehistoric couplings. —Gretchen VogelHow do multiple actors inside a cell get to-
gether at the right place and time to perform
critical functions? Often the answer, bio-
logists are coming to realize, is liquid drop-
lets. Unseen until recently, they are show-
ing up everywhere in cells, organizing (and
sometimes gumming up) the works.
Tens of thousands of proteins and other
molecules populate the cytoplasm, the thick
liquid that surrounds the cell nucleus, often
jostling each other and reacting to perform
the tasks of life, from breaking down nutri-
ents to liberating energy to recycling waste.
Beginning in 2009, researchers discovered
that many proteins separate, or condense,
into discrete droplets, concentrating their
contents, especially when the cell is respond-
ing to stress. This “liquid-liquid phase separa-
tion,” analogous to the “demixing” of oil and
vinegar in a vinaigrette salad dressing, is now
one of the hottest topics in cell biology, as
evidence accumulates that it promotes criti-
cal biochemical reactions and appears to be
a basic organizing principle of the cell.
Two 2017 papers in Nature had shown liq-
uid protein droplets in the cell nucleus help
compact regions of the genome, silencingthe genes within. This year, three papers
in Science pointed to an even bigger role
for phase separation. They showed pro-
teins that drive the transfer of the genetic
code from DNA to RNA—the first step in
making new proteins—can condense into
droplets that attach to the DNA. Details
remain to be worked out, but these studies
reveal a role for phase separation in one of
life’s fundamental mysteries, the selective
expression of genes.
Biophysicists are working out how these
droplets form. Certain classes of proteins
trail spaghettilike tails that interact totrigger the condensation. But when the
process goes awry, what should be a liquid
can become a gel, and a gel can solidify,
forming the kinds of aggregates seen in
neurodegenerative diseases such as amyo-
trophic lateral sclerosis. A March Science
paper showed this happening when such
proteins are improperly excluded from the
cell nucleus. In April, four papers in Cell
revealed possible measures for dissolving
the toxic aggregates, and several labs are
now trying to exploit this knowledge to dis-
cover drugs for treating neurodegenerative
diseases. —Ken GarberKen Garber is a journalist in
Ann Arbor, Michigan.How cells marshal their contents
An archaic human ‘hybrid’
BREAKTHROUGH OF THE YEAR | RUNNERS-UP 2018
IMAGES: (TOP TO BOTTOM) THOMAS HIGHAM/UNIVERSITY OF OXFORD; E. M. LANGDON
ET AL
., SCIENCE
2018
A bone fragment found in a cave in the Denisova valley in Russia.Liquid droplets formed from protein and RNA are emerging as a new form of cellular organization.Published by AAASon December 24, 2018^http://science.sciencemag.org/Downloaded from