Startling Reflections in the Neanderthal Genome.

by Kenneth W. Krause.

Kenneth W. Krause is a contributing editor and “Science Watch” columnist for the Skeptical Inquirer.  Formerly a contributing editor and books columnist for the Humanist, Kenneth contributes regularly to Skeptic as well.  He may be contacted at

Considered neither chic nor sleek, Neandertals were once the Richard Nixons of extinct hominins.  But thanks to a newly published draft sequence of our (kissing?) cousins’ nuclear genome, we don’t have Neandertals to kick around anymore.  In fact, one could argue—as Svante Pääbo, paleogeneticist at the Max Planck Institute in Leipzig, Germany, and leader of project recently has—that Neandertals aren’t really extinct at all.


Modern humans and Neandertals share a common ancestor that lived from between 270,000 and 400,000 years ago, according to Pääbo’s new estimate.  The latter lived in Europe and Asia—only as far east as Southern Siberia and only as far south as the Middle East.  Fossil evidence suggests the two groups encountered one another in some way in the Middle East from at least 80,000 years ago, and then later in Europe.  But, for reasons highly contested and yet unclear, H. sapiens pressed on as Neandertal remains vanished from the record around 28,000 years ago.

Burly and bell-chested with protruding brow-ridges and feeble chins, Neandertals have suffered much abuse in the popular imagination.  Crude tradition has portrayed them as dullards because of their brutish appearance, for example, or as one-trick-ponies because of their inability to survive irregular climatic circumstances or, alternatively, the invasion of Cro-Magnon man during the late Pleistocene.

But science has recently rehabilitated the Neandertal narrative.  For whatever it’s worth, their brains were probably as large or larger than ours.  Apparently gifted with symbolic thought, they decorated their bodies with jewelry and probably pigment.  They hunted expertly with stone points and implements crafted from wood and bone.  In 2007, Johannes Krause (also a member of Pääbo’s team) reported that Neandertals carried FOXP2, the gene that allows humans to speak.  And whatever the causes of their eventual passing, Neandertals ruled Eurasia’s volatile environs for more than 200,000 years—longer than our species has existed.

But the biggest news has just arrived.  Neandertals, it turns out, are human—or at least a significant portion of most humans.  In the May 7 issue of Science, Pääbo’s international team of scientists published a draft sequence of the Neandertal genome composed of 4 billion nucleotides from three individuals.  And to their great surprise, they discovered that between 1 and 4 percent of the modern, non-African human genome was derived from our maligned and misunderstood relatives.  In other words, Neandertals and modern humans interbred.

The outcome stunned Pääbo and his cohorts because previous analyses of Neandertal mitochondrial DNA consistently fell outside the variation found in contemporary humans.  On the other hand, many paleoanthropologists rather expected the results.  Milford Wolpoff of the University of Michigan and João Zilhão of the University of Bristol in England, argue that fossil evidence has long suggested interbreeding.  Found in Portugal in the late 1990s, for example, the 24,000-year-old Lagar Velho child presents a mixture of Neanderthal and H. sapiens traits.

Pääbo’s team assembled the genome primarily using DNA from three Neandertal limb bones—each from a separate female individual—found in Vindija Cave, Croatia, and dated to 38,000 to 44,000 years old.  They confirmed that sequence with smaller samples from El Sidron, Spain; Neander Valley, Germany; and Mezmaiskaya, Russia—none of which differed significantly from the Vindija specimens.  By contrasting the results with the chimpanzee genome, Pääbo was able to distinguish ancestral genetic variants from their derived counterparts.

To find out whether Neandertals are more closely related to some contemporary humans than to others, Pääbo then compared the derived Neandertal variants to those contained in the genomes of five living humans—a San from Southern Africa, a Yoruba from West Africa, a French European, a Papua New Guinean, and a Han Chinese.  The San and Yoruba were deemed appropriate proxies for genetic diversity in Africa because of their exceptionally ancient heritage. If gene flow between Neandertals and H. sapiens occurred prior to differentiation among human populations, Pääbo hypothesized, the Neandertal alleles would match those of individuals from some regions of the world more often than those of others.


And the results revealed exactly that.  After ruling out the ever-present possibility of contamination, the team concluded that “Neandertals share significantly more derived alleles with non-Africans than with Africans.”  More specifically, Neandertals shared the same number of derived alleles with both the European and the Asians, but significantly more with either the European or the Asians compared with either African.  Notably, no Neandertal specimen has ever been found as far east as China or New Guinea.

Thus, Pääbo inferred, because Neandertals are more closely related to all present-day non-Africans, and equally so, they must have interbred with their common ancestors shortly after they departed from Africa into the Middle East, but before their further migration into Eurasia.  Such genetic exchange could have taken place about 80,000 years ago when Neandertal remains began to show up in Israeli caves already occupied by humans (Qafzeh, Skhul, and Tabun, for example), or later, about 50,000 to 60,000 years ago, when a second group of H. sapiens set out from Africa.  Even so, the team wouldn’t completely exclude an alternative possibility—that their results might instead reveal an “old substructure” in Africa that lasted from Neanderthal origins until non-African migration.

In any case, a prominent and long-standing debate in paleoanthropology has finally been resolved.  The Neandertal genome does indeed live on in present-day humans.  But “the most interesting development,” Pääbo recently told me, may be “the identification of genes that were positively selected in humans after their divergence from Neanderthals.”  In other words, the Neandertal sequence has begun to reveal some of the recently evolved traits that make us uniquely human.

But there were surprises lurking here too.  Using the chimpanzee, orangutan, and rhesus macaque genomes in addition to those of modern humans and Neandertals, the team located only 78 recent nucleotide substitutions capable of altering the protein-coding capacity of genes where moderns are fixed for a derived state and where Neandertals bear the ancestral, more chimp-like version.  And just five genes had accumulated multiple substitutions—a shockingly small number, given the ample span of time.  Indeed, changes to human accelerated regions (HARs)—conserved throughout most of vertebrate evolution, but altered drastically during hominin evolution—tended to predate the human-Neandertal split.

Even so, Pääbo was able to identify general roles, if not specific functions, associated with some of our newly altered genes.  Three alleles carrying multiple substitutions affect skin physiology, including pigmentation (TRPM1).  Others might pertain to cognitive development, mutations of which are presently implicated in causing autism (CADPS2, AUTS2), schizophrenia (NRG3), and Downs syndrome (DYRK1A).  Still others could be important for gene transcription (TTF1), wound healing (PCD16), energy metabolism (THADA), and the beating of the sperm flagellum (SPAG17).

The team couldn’t say, however, whether these specific substitutions were the result of random drift or positive selection.  But they also searched the modern human sequence for “selective sweeps”—lengthy swaths of DNA including mutations absent in the Neandertal and chimp genomes.  Extensive affected regions, the prevailing theory goes, imply relatively intense selective pressures.  Again through genomic comparisons, Pääbo successfully identified 212 such sweeps in the modern human genome, many surrounding genes commonly thought to involve brain function in some way.

But the new Neandertal sequence is imperfect to say the least.  Although Pääbo’s team decoded roughly 5.3 billion nucleotides in total—the human genome containing about 3 billion—much of that total consists of duplications.  They confess as well that better than a third of the genome remains unsequenced.  Pääbo expects his fair share criticism at some point, but says it’s a bit too early to expect serious reproaches from other scientists.  The religious community remains silent as well, which Pääbo finds somewhat surprising.

Meanwhile, science turns its collective gaze forward.  Pääbo wants to improve the screening process for positive selection and to follow up on specific candidate genes the function of which may have been altered during recent human evolution.  He hopes as well to explore the Neandertal sequence more fully to identify features unique to their species (or subspecies), and to illuminate Neandertal variation by analyzing the remains of additional specimens.  And perhaps his team will scrutinize the genomes of other extinct hominin forms to determine whether they too have contributed to the human blueprint.

Regardless, Pääbo and his colleagues have already advanced humanity’s self-knowledge by meteoric leaps and bounds.  We now have confirmation that the genomes of long-extinct hominins can be reliably salvaged.  We know that the strictest “out of Africa” hypothesis of human origins is untenable, and that the environment—whether natural or man-made—continues to shape the contours our epic evolutionary adventure.  We should appreciate as well that genetic rifts between modern human populations can run quite deep indeed, and, thus, will be ignored only at our common peril.

And hopefully we’ve gained a great deal more respect for our exceptionally intimate relatives, the Neandertals.  Far from ugly, dim-witted, or incompetent, our “sister group,” as Pääbo’s team has dubbed them, will much to teach us in the coming years.  But many of us can’t really talk about Neandertals as “them” anymore, because, in fact, Neandertals are us.


3 thoughts on “Startling Reflections in the Neanderthal Genome.

  1. John

    Sweet article! I will never understand why Neanderthals are still considered a separate species when they apparently successfully interbred with H sapiens. And Denisovans. Could the three be categorized as different subspecies?



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