We’re still grappling with the astonishing 2010 discovery that Neanderthals had mated with modern humans [1]. Now two new studies published earlier this year [2, 3] have identified the Neanderthal contributions to our present-day genomes, and also provided evidence that our Neanderthal legacy may be a mixed bag of beneficial and deleterious traits.

Neanderthal-Homo sapiens Sex: Does it Matter?

The sequencing of the complete Neanderthal genome in 2010 by Svante Pääbo’s group at the Max Planck Institute of Evolutionary Anthropology revealed that modern humans share about 2.5% of their genome with Neanderthals [1], a number that has since been corroborated by a second, more precise Neanderthal genome sequenced by the same group in 2014 [4]. Interestingly, only living Europeans and Asians, but not Africans, have Neanderthal DNA. Because modern humans are thought to have originated in Africa, scientists surmise that early Homo sapiens encountered and interbred with the Neanderthals about 40,000 to 80,000 years ago as they expanded out of Africa into Europe and Asia where the Neanderthals ranged [5].

Figure 1 ~  Interbreeding between Homo sapiens and other early hominid species.  For the purpose of clarity, interbreeding between Neanderthals, Denisovans, and a putative unknown hominid species are not shown here.  1Because only one fossil of Denisovans – the bone of a pinky – has been found so far (in Siberia), it is unclear where and how far Denisovans ranged when they first encountered early humans. However, scientists think they were at least in parts of Asia, since Melanesians carry 5% of Denisovan DNA in their genomes

Since then, researchers have sought to determine the impact of these Neanderthal genetic remnants on people today. Earlier work suggested that some of the genes inherited from Neanderthals and other archaic humans are involved in coping with ultraviolet radiation and the functioning of our immune system [6]. However, no one has yet looked systematically at the identity of these Neanderthal genes across the entire human genome and across a large swath of extant human populations. That is, until now.

Reconstructing Neanderthal Contributions to Living Human Genomes

In the first study, a research group led by Harvard Medical School population geneticist David Reich used computational methods to scour the Homo sapiens genome for Neanderthal DNA. To do this, they compared the genomic sequence of a 50,000-year-old Neanderthal woman[4] to hundreds of genomes of modern Africans, Europeans, and Asians available in a public database [7].

Like Reich’s group, a second team of researchers led by Joshua Akey at the University of Washington also used information from the same genetic repository – the 1000 Genomes Project – to devise an algorithm for detecting Neanderthal DNA in present-day humans. However, in contrast to Reich’s approach, Akey’s algorithm did not require the use of the existing Neanderthal genome but relied more on the analysis of genetic differences between living Africans and non-Africans. Both teams observed an average of about 2% Neanderthal ancestry in modern non-African genomes, but they found different individuals have widely varying Neanderthal genes. In fact, present-day humans collectively carry more than a fifth of the entire Neanderthal genome – much more than scientists have previously estimated.

The Good and the Bad of Our Neanderthal Ancestry

Intriguingly, the distribution of Neanderthal DNA across the human genome is far from uniform. Both Reich’s and Akey’s teams found a substantial enrichment of Neanderthal contributions to genes involved in the formation of keratin filaments, which are critical components of hair and skin. Neanderthals lived in the colder climes of Europe and western Asia and could have evolved adaptations that helped them survive the lower temperatures. Possible adaptations include changes to the skin and hair that improved thermal insulation and resistance to pathogens. The authors speculated that the Neanderthal genes involved in keratin production may have been preserved in humans moving out of Africa into Eurasia because the genes conferred an advantage in the cooler climate.

Not everything that humans inherited from the Neanderthals was beneficial though. Some of the genes identified by Reich as Neanderthal in origin have previously been associated with assorted conditions including type 2 diabetes, lupus, Crohn’s disease (a type of intestinal inflammation), and even cigarette addiction.

Both research teams also found chromosomal regions in modern human genomes that were depleted of Neanderthal ancestry. These Neanderthal-deficient “deserts” often contain genes that are highly expressed in the testes and situated on the X chromosome – one of the two chromosomes that determine the sex of the individual (the other one being the Y chromosome). Such a pattern of gene deserts and oases might have happened if early humans who harbored Neanderthal DNA on the X chromosome suffered from diminished fertility, causing the responsible genes to be expunged from the human genome over time.

Beyond Neanderthals to Denisovans and Other Ancients

Before we start blaming the Neanderthals for our bad hair or chain-smoking habits, both Reich and Akey caution that many of the exact functions of the extant Neanderthal gene variants remain obscure [6]. Moreover, the effects of these genes – such as those associated with diseases – may be different between Neanderthals and humans, and between early Neanderthal-human hybrids and people today (which could explain why the Neanderthals retained those genes). Nonetheless, Reich argues that the selective enrichment and depletion of Neanderthal ancestry in our modern genomes is too strong to be explained solely by chance, and must involve some degree of natural selection for or against specific Neanderthal features [2]. So while the biology of these Neanderthal genes is poorly understood, scientists now have an inventory of genes from which to begin their investigation.

Neanderthals are not even the only ancient human species with whom our Homo sapiens ancestors mated. Recent fossil discoveries and genomic sequencing have identified at least two other now-extinct human species that were contemporary with Homo sapiens as early humans started their long trek out of Africa [5, 8]. One of these species includes the Denisovans, who lived in Asia up to about 30,000 years ago and whose DNA survives in about 5% of modern Melanesians [5]. The second archaic human species is not even known to scientists through fossils or archaeological remains! Instead, its (still debated) existence was inferred from the comparison of the genomes of Denisovans, Neanderthals and modern humans, which unearthed evidence of Denisovans interbreeding with a mysterious ancient human group [8].

What genes have these (and other still-unknown) archaic humans imparted to us, and why have we retained them? Akey’s bioinformatic approach managed to identify Neanderthal contributions without the need for a reference Neanderthal genome. This suggests that scientists may soon be able to deduce the genetic contributions from hitherto unknown human species to living people based on the readily accessible genomes of present-day populations. More excitingly, researchers may thence be able to infer significant information about the genomes and characteristics of archaic humans, independently of the discovery of fossils.

Neanderthals and other ancient humans have been living on in secret within us for generations. But we are slowly and surely unveiling their presence, and in so doing, discovering more about our extinct forebears as well as ourselves.

Tze G. Tan is a graduate student at Harvard Medical School.


[1] Nicholas Wade. “Signs of Neanderthals Mating With Humans”. The New York Times Science Section. http://www.nytimes.com/2010/05/07/science/07neanderthal.html?mabReward=relbias:r&action=click&adxnnl=1&region=searchResults&module=Search&url=http://query.nytimes.com/search/sitesearch/?action=click&region=Masthead&pgtype=Homepage&module=SearchSubmit&contentCollection=Homepage&t=qry941#/Neanderthal&adxnnlx=1399522775-M4UYepmpHSqK4Hb6o2vl0g

[2] Sankararaman S et al. “The genomic landscape of Neanderthal ancestry in present-day humans” 2014. Nature 507: 354-7. http://www.nature.com/nature/journal/v507/n7492/full/nature12961.html

[3] Vernot B & Akey JM. “Resurrecting Surviving Neandertal Lineages from Modern Human Genomes” 2014. Science 343: 1017-21. http://www.sciencemag.org/content/343/6174/1017.abstract

[4] Prufer K et al. “The complete genome sequence of a Neanderthal form the Altai Mountains” 2010. Nature 505(7481): 43-49. http://www.nature.com/nature/journal/v505/n7481/full/nature12886.html

[5] Earlier SITN article that reviews the discoveries of genetic admixture between early Homo sapiens and archaic humans, including the Neanderthals and Denisovans:


[6] Callaway E. “Modern human genomes reveal our inner Neanderthal” 2014. Nature News. http://www.nature.com/news/modern-human-genomes-reveal-our-inner-neanderthal-1.14615

[7] The home-page of the 1000 Genomes Project, which maintains a database of modern human genomes towards the end of cataloging the extensive genetic variation across individuals of different ethnicities. http://www.1000genomes.org/about

[8] Birney E & Pritchard JK. “Archaic humans: Four makes a party” 2014. Nature News & Views 505(7481). http://www.nature.com/nature/journal/v505/n7481/full/nature12847.html




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