Archaic human admixture with modern Homo sapiens
Archaic human admixture with modern Homo sapiens occurred at least twice in history: with Neanderthals, and with the population to which the Denisova hominin belonged. A minimum estimated 1% to 4% of the DNA in Eurasians is non-modern and shared with ancient Neanderthal DNA rather than with sub-Saharan Africans (i.e. Yoruba and San probands). A minimum additional estimated 4–6% of Melanesian DNA is from the archaic Denisovan hominins from Asia. Recent DNA analysis also indicates African admixture with a now extinct archaic population.
Various theories of Neanderthal admixture in modern human DNA, i.e. the result of interbreeding of Neanderthals and anatomically modern humans during the Middle Paleolithic have been debated throughout the 20th century, and in terms of genetics throughout the 2000s. In March 2013, new data from the Mezzena mandible (Monti Lessini, Italy) indicated possible interbreeding (sapiens/neanderthal hybrid) in late Italian Neanderthals.
In May 2010, the Neanderthal Genome Project presented preliminary genetic evidence that interbreeding did likely take place and that a small but significant portion of Neanderthal admixture is present in modern non-African populations. The interbreeding hypothesis is a controversially discussed scenario of Neanderthal extinction, the disappearance of Neanderthal traits from the fossil record about 30,000 years ago. Nonetheless, and according to recent genetic studies on genomic DNA, modern humans seem to have mated with "at least two groups" of ancient humans: Neanderthals and Denisovans. However, modern humans do not share any mitochondrial DNA with the Neanderthals, an observation that puts constraints on the possible types of successful mating patterns, since mitochondrial DNA in primates is exclusively maternally transmitted.
The hypothesis, variously under the names of interbreeding, hybridization, admixture or hybrid-origin theory, has been discussed ever since the discovery of Neanderthal remains in the 19th century, though earlier writers believed that Neanderthals were a direct ancestor of modern humans. Thomas Huxley suggested that many Europeans bore traces of Neanderthal ancestry, but associated Neanderthal characteristics with primitivism, writing that since they "belong to a stage in the development of the human species, antecedent to the differentiation of any of the existing races, we may expect to find them in the lowest of these races, all over the world, and in the early stages of all races".
Hans Peder Steensby in the article Race studies in Denmark (1907) rejected that Neanderthals were ape-like or inferior, and, while emphasizing that all modern humans are of mixed origins, suggested interbreeding as the best available explanation of a significant number of observations which by then were available.
In the early twentieth century, Carleton Coon argued that the Caucasoid race is of dual origin consisting of Upper Paleolithic (mixture of H. sapiens and neanderthalensis) types and Mediterranean (purely H. sapiens) types. He repeated his theory in his 1962 book The Origin of Races.
Stan Gooch in Personality and Evolution (1973) and The Neanderthal Question (1977) develops a theory of Neanderthal/Cro-Magnon hybridization, based not on an examination of anatomy but of his understanding of modern human psychology and society, which he claimed owes a significant debt to Neanderthal culture. Gooch's theories were dismissed by academia. Gooch refined his theory in Cities of Dreams (1989) and The Neanderthal Legacy (2008).
The question of Neanderthal/Cro-Magnon hybridization is reflected in 20th century popular culture, in works such as La Guerre du feu (1911), Dance of the Tiger (1978, 1980) by Finnish palaeontologist Björn Kurtén, and the Earth's Children series by Jean M. Auel, published from 1980.
A draft sequence publication by the Neanderthal Genome Project in May 2010 indicates that Neanderthals share more genetic lineages with Eurasian populations than with sub-Saharan Africans. According to the study, this scenario is best explained by gene flow from Neanderthals to modern humans after humans emerged from Africa and before the divergence of the Eurasian groups. An estimated 1–4% of the DNA in Europeans and Asians (e.g. French, Chinese and Papua probands) is non-modern and shared with ancient Neanderthal DNA rather than with Sub-Saharan Africans (e.g. Yoruba and San probands). Though less parsimonious than gene flow, ancient sub-structure in Africa, could account for the higher levels of Neanderthal lineages detected in Eurasians. Some researchers suggest admixture of 3.4%-7.9% in Eurasian populations, rejecting the hypothesis of ancestral population structure.
No evidence supporting this has been found in mitochondrial DNA analyses of modern Europeans, suggesting at least that no direct maternal line originating with Neanderthals has survived into modern times.
Recent studies have shown a higher Neanderthal admixture in East Asians when compared to Europeans. It indicated that most-likely at least two independent events of gene flow must have taken place into modern humans and that the ancestors of modern East Asians experienced more admixture than those of modern Europeans after the divergence of the two groups. It is also possible, but less likely, that the difference was caused by dilution in Europeans by later migrations out of Africa.
A 2012 study found that modern North Africans have a Neandertal admixture lying between that of modern Eurasians and modern sub-Saharan Africans. It has also shown a great variation within modern North Africans itself, depending primarily on the amount of European and near East ancestry versus sub-Saharan African ancestry.
Variation in microcephalin, a critical regulator of brain size whose loss-of-function by damaging mutations may also cause primary microcephaly, was claimed to be the strongest evidence of admixture as of 2007. One type of the gene, known as D, has a high worldwide frequency (~70%), but a young coalescence age to its most recent common ancestor, ~37,000 years ago. The remaining types (non-D) coalesce to ~990,000 years ago, while the separation time between D and non-D is estimated at ~1,100,000 years ago. An evolutionary advantage of D is possible but controversial.
The distribution of the D allele, high outside Africa but low in sub-Saharan Africa (29%), has been suggested to indicate involvement of an archaic Eurasian population, and estimates of the divergence time between modern humans and Neanderthals based on mitochondrial DNA are in favor of the Neanderthal lineage as the most likely archaic Homo population from which introgression into the modern human gene pool took place. However, according to Svante Pääbo, ancient DNA from Croatian Neanderthal fossils found at Vindija shows that they carried the non-D allele of microcephalin, and there is no evidence for admixture or introgression. A study published in May 2010 found that a Neanderthal individual from Mezzena Rockshelter (Monti Lessini, Italy), possessed the ancestral version of D, rather than the derived version which is common among Eurasian populations. The study did not rule out interbreeding between Neanderthals and modern humans but indicated that the particular DNA sample provided no support to the theory that Neanderthals contributed the derived allele of D to modern humans.
Based on a 2001 study of the gene that results in red-headedness, some commentators speculated that Neanderthals had red hair and that some red-headed and freckled humans today share some heritage with Neanderthals. A 2007 study analysing Neanderthal DNA found that some Neanderthals were red-haired, but the mutation to the MC1R gene which caused red hair in Neanderthals is not found in modern humans.
There is evidence that some immune related genes are of Neanderthal origin. HLA-C*0702, found in Neanderthals, is common in modern Europeans and Asians but rarely seen in Africans. It is thought that this immune gene may have been picked up by humans after leaving Africa to help deal with European diseases that the Neanderthals had evolved defenses for.
The most vocal proponent of the hybridization hypothesis on anatomical grounds has been Erik Trinkaus of Washington University. Trinkaus claims various fossils as hybrid individuals, including the "child of Lagar Velho", a skeleton found at Lagar Velho in Portugal dated to about 24,000 years ago. In a 2006 publication co-authored by Trinkaus, the fossils found in 1952 in the cave of Peștera Muierii, Romania, are likewise claimed as hybrids. 
In his work Neanderthal, Paul Jordan points out that without some interbreeding, certain features on some "modern" skulls of Eastern European Cro-Magnon heritage are hard to explain. In another study, researchers have recently found in Peştera Muierilor, Romania, remains of European humans from 30 thousand years ago who possessed mostly diagnostic "modern" anatomical features, but also had distinct Neanderthal features not present in ancestral modern humans in Africa, including a large bulge at the back of the skull, a more prominent projection around the elbow joint, and a narrow socket at the shoulder joint. Analysis of one skeleton's shoulder showed that these humans, like Neanderthal, did not have the full capability for throwing spears.
The paleontological analysis of modern-human emergence in Europe has been shifting from considerations of the Neanderthals to assessments of the biology and chronology of the earliest modern humans in western Eurasia. This focus, involving morphologically modern humans before 28,000 years ago, shows accumulating evidence that they present a variable mosaic of derived modern human, archaic human, and Neanderthal features. Studies of fossils from the upper levels of the Sima de las Palomas, Murcia, Spain, dated to 40,000 years ago, establish the late persistence of Neanderthals in Iberia. This reinforces the conclusion that the Neanderthals were not merely swept away by advancing modern humans. In addition, the Palomas Neanderthals variably exhibit a series of modern-human features rare or absent in earlier Neanderthals. Either they were evolving on their own towards the modern-human pattern, or more likely, they had contact with early modern humans around the Pyrenees. If the latter is the case, it implies that the persistence of the Middle Paleolithic in Iberia was a matter of choice, and not cultural retardation.
Modern-human findings in Abrigo do Lagar Velho, Portugal, of 24,500 years ago, allegedly featuring Neanderthal admixtures, have been published. However the interpretation of the Portuguese specimen is disputed.
Tests comparing the Denisova hominin genome with those of six modern humans – a ǃKung from South Africa, a Nigerian, a Frenchman, a Papua New Guinean, a Bougainville Islander and a Han Chinese – showed that between 4% and 6% of the genome of Melanesians (represented by the Papua New Guinean and Bougainville Islander) derives from a Denisovan population. This DNA was possibly introduced during the early migration to Melanesia. These findings are in concordance with the results of other comparison tests which show a relative increase in allele sharing between the Denisovan and the Aboriginal Australian genome, compared to other Eurasians and African populations, however it has been observed that Papuans, the population of Papua New Guinea, have more allele sharing than Aboriginal Australians.
Melanesians may not be the only modern-day descendants of Denisovans. David Reich of Harvard University, in collaboration with Mark Stoneking of the Planck Institute team, found genetic evidence that Denisovan ancestry is shared by Melanesians, Australian Aborigines, and smaller scattered groups of people in Southeast Asia, such as the Mamanwa, a Negrito people in the Philippines. However, not all Negritos were found to possess Denisovan genes; Onge Andaman Islanders and Malaysian Jehai, for example, were found to have no significant Denisovan inheritance. These data place the interbreeding event in mainland Southeast Asia, and suggest that Denisovans once ranged widely over eastern Asia.
Melanesians thus emerge as the most "archaic"-admixed population, having Denisovan/Neandertal-related admixture of ~8%.
The immune system's HLA alleles have drawn particular attention in the attempt to identify genes that may derive from archaic human populations. Although not present in the sequenced Denisova genome, the distribution pattern and divergence of HLA-B*73 from other HLA alleles has led to the suggestion that it introgressed from Denisovans into humans in west Asia. Indeed, half of the HLA alleles of modern Eurasians represent archaic HLA haplotypes, and have been inferred to be of Denisovan or Neanderthal origin. The apparent over-representation of these alleles suggests a positive selective pressure for their retention in the human population.
Unknown Sub-Saharan African hominin
In 2011 Michael Hammer et al. at the University of Arizona studied DNA from two African hunter-gatherer groups, the Biaka Pygmies, the San and the West African agricultural Mandinka people. They concluded that roughly 2% of the genetic material found in these modern African populations was inserted into the human genome approximately 35,000 years ago. They also concluded these sequences must have come from a now-extinct member of the Homo genus that broke away from the modern human lineage around 700,000 years ago.
In 2012 another study was done by Sarah Tishkoff et al. at the University of Pennsylvania. They tested 3 sub-Saharan African populations - Pygmies from Cameroon and the Hadza and Sandawe, both from Tanzania. The team found signs that the ancestors of the hunter-gatherers bred with different species of hominins, probably more than 40,000 years ago.
- Archaic Homo sapiens
- Neanderthal Genome Project
- Denisova hominin
- Multiregional hypothesis
- Chris Stringer: Comment: What makes a modern human. In: Nature. Vol. 485, No. 7396, 2012, pp. 33–35 (here p. 34), doi:10.1038/485033a
- Michael F. Hammer et al.: Genetic evidence for archaic admixture in Africa. In: PNAS. Band 108, Nr. 37, 2011, S. 15123–15128, doi:10.1073/pnas.1109300108
- Green, Richard E., et al. (7 May 2010). "A Draft Sequence of the Neandertal Genome". Science 328 (5979): 710–722. Bibcode:2010Sci...328..710G. doi:10.1126/science.1188021. PMID 20448178.
- "NEANDERTALS LIVE!". john hawks weblog. Archived from the original on 16 December 2010. Retrieved 31 December 2010.
- Reich, David; Green, Richard E.; Kircher, Martin; Krause, Johannes; Patterson, Nick; Durand, Eric Y.; Viola, Bence; Briggs, Adrian W.; Stenzel, Udo; Johnson, Philip L. F.; Maricic, Tomislav; Good, Jeffrey M.; marques-Bonet, Tomas; Alkan, Can; Fu, Qiaomei; Mallick, Swapan; Li, Heng; Meyer, Matthias; Eichler, Evan E.; Stoneking, Mark; Richards, Michael; Talamo, Sahra; Shunkov, Michael V.; Derevianko, Anatoli P.; Hublin, Jean-Jacques; Kelso, Janet; Slatkin, Montgomery & Pääbo, Svante (2010), "Genetic history of an archaic hominin group from Denisova Cave in Siberia", Nature 468 (7327): 1053–1060, Bibcode:2010Natur.468.1053R, doi:10.1038/nature09710, PMID 21179161
- Michael F. Hammer et al. (27 July 2011). "Genetic evidence for archaic admixture in Africa". PNAS.
- Fagundes, Nelson J. R.; Nicolas Ray, Mark Beaumont, Samuel Neuenschwander, Francisco M. Salzano, Sandro L. Bonatto and Laurent Excoffier (2007). "Statistical evaluation of alternative models of human evolution". PNAS (The National Academy of Sciences of the USA) 104 (45): 17614–17619. Bibcode:2007PNAS..10417614F. doi:10.1073/pnas.0708280104. PMC 2077041. PMID 17978179.
- Hodgson JA, Disotell TR (2008). "No evidence of a Neanderthal contribution to modern human diversity". Genome Biol. 9 (2): 206. doi:10.1186/gb-2008-9-2-206. PMC 2374707. PMID 18304371.
- Laura Longo, Silvana Condemi; Aurèlien Mounie, Paolo Giunti, Martina Lari, David Caramelli (27). "Possible Interbreeding in Late Italian Neanderthals? New Data from the Mezzena Jaw (Monti Lessini, Verona, Italy)". PLoS ONE 8 (3). Bibcode:2013PLoSO...859781C. doi:10.1371/journal.pone.0059781. Retrieved 3 April 2013.
- Mitchell, Alanna (30 January 2012). "DNA Turning Human Story Into a Tell-All". NYTimes. Retrieved 31 January 2012.
- Krings M, Stone A, Schmitz RW, Krainitzki H, Stoneking M, Pääbo S. (1997). "Neandertal DNA sequences and the origin of modern humans". Cell 90 (1): 19–30. doi:10.1016/S0092-8674(00)80310-4. PMID 9230299.
- Paul H. Mason, Roger V. Short (2011). "Neanderthal-human Hybrids". Hypothesis 9: e1.
- Thomas Huxley, The Aryan Question and Pre-Historic Man (1890), Collected Essays VII.
- Coon, Careton, The Origin of Races, From Neanderthal to Nordic in Wuerm I", 1962, page 529.
- R. E. Green et al. (2010). "A Draft Sequence of the Neandertal Genome". Science 328 (5979): 710–722. Bibcode:2010Sci...328..710G. doi:10.1126/science.1188021. PMID 20448178.
- Lohse, Konrad; Frantz, Laurent A.F. (July 31, 2013). "Maximum likelihood evidence for Neandertal admixture in Eurasian populations from three genomes". Cornell University.
- Krings M, Stone A, Schmitz RW, Krainitzki H, Stoneking M, Pääbo S (July 1997). "Neandertal DNA sequences and the origin of modern humans". Cell 90 (1): 19–30. doi:10.1016/S0092-8674(00)80310-4. PMID 9230299.
- No Neandertals in the Gene Pool, Science (2004).
- Serre, D; Langaney, A; Chech, M; Teschler-Nicola, M; Paunovic, M; Mennecier, P; Hofreiter, M; Possnert, G et al. (2004). "No evidence of Neandertal mtDNA contribution to early modern humans". PLoS Biology 2 (3): 313–7. doi:10.1371/journal.pbio.0020057. PMC 368159. PMID 15024415.
- Meyer, M.; Kircher, M.; Gansauge, M.-T.; Li, H.; Racimo, F.; Mallick, S.; Schraiber, J. G.; Jay, F.; Prufer, K.; de Filippo, C.; Sudmant, P. H.; Alkan, C.; Fu, Q.; Do, R.; Rohland, N.; Tandon, A.; Siebauer, M.; Green, R. E.; Bryc, K.; Briggs, A. W.; Stenzel, U.; Dabney, J.; Shendure, J.; Kitzman, J.; Hammer, M. F.; Shunkov, M. V.; Derevianko, A. P.; Patterson, N.; Andres, A. M.; Eichler, E. E.; Slatkin, M.; Reich, D.; Kelso, J.; Paabo, S. (30 August 2012). "A High-Coverage Genome Sequence from an Archaic Denisovan Individual". Science 338 (6104): 222–226. doi:10.1126/science.1224344.
- Wall, J. D.; Yang, M. A.; Jay, F.; Kim, S. K.; Durand, E. Y.; Stevison, L. S.; Gignoux, C.; Woerner, A.; Hammer, M. F.; Slatkin, M. (14 February 2013). "Higher Levels of Neanderthal Ancestry in East Asians than in Europeans". Genetics 194 (1): 199–209. doi:10.1534/genetics.112.148213.
- Sanchez-Quinto et al., "North African Populations Carry the Signature of Admixture with Neanderthals", October 17, 2012 http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0047765
- Mekel-Bobrov, N. et al. (2007). "The ongoing adaptive evolution of ASPM and Microcephalin is not explained by increased intelligence". Hum. Mol. Genet. 16 (6): 600–8. doi:10.1093/hmg/ddl487. PMID 17220170.
- Evans, Patrick D.; et al. (7 November 2006). "Evidence that the adaptive allele of the brain size gene microcephalin introgressed into Homo sapiens from an archaic Homo lineage". PNAS 103 (48): 18178–18183. Bibcode:2006PNAS..10318178E. doi:10.1073/pnas.0606966103. PMC 1635020. PMID 17090677. Archived from the original on 13 May 2008. Retrieved 26 May 2008.
- Evans, Patrick D.; et al. (9 September 2005). "Microcephalin, a Gene Regulating Brain Size, Continues to Evolve Adaptively in Humans". Science 309 (5741): 1717–1720. Bibcode:2005Sci...309.1717E. doi:10.1126/science.1113722. PMID 16151009.
- Morgan, James (12 February 2009). "Neanderthals 'distinct from us'". BBC News. Retrieved 11 October 2009.
- Gitlin, Jonathan M. (23 February 2009). "A Neanderthal in the family: working with ancient DNA". Ars Technica. Retrieved 11 October 2009.
- Lari, Martina; Rizzi, Ermanno; Milani, Lucio; Corti, Giorgio; Balsamo, Carlotta; Vai, Stefania; Catalano, Giulio; Pilli, Elena et al. (2010). "The Microcephalin Ancestral Allele in a Neanderthal Individual". In Hawks, John. PLoS ONE (PLoS ONE) 5 (5): e10648. Bibcode:2010PLoSO...510648L. doi:10.1371/journal.pone.0010648. PMC 2871044. PMID 20498832.
- Red hair a legacy of Neanderthal man
- "Red-Heads and Neanderthals". May 2001. Archived from the original on 18 October 2005. Retrieved 28 October 2005.
- "Nicole's hair secrets". The Daily Telegraph (London). 10 February 2002. Archived from the original on 11 December 2005. Retrieved 2 November 2005.
- Rincon, Paul (25 October 2007). "Neanderthals 'were flame-haired'". BBC.
- "Populations of Sub-Saharan Africa sorted by C*0702 allele frequency". The Allele Frequency Net Database. Retrieved January 2012.
- Marshall, Michael (16 June 2011). "Breeding with Neanderthals helped humans go global". New Scientist. Retrieved January 2012.
- Dan Jones: The Neanderthal within., New Scientist 193.2007, H. 2593 (3 March), 28–32. Modern Humans, Neanderthals May Have Interbred; Hayes, Jacqui (2 November 2006). "Humans and Neanderthals interbred, according to our anatomy". Retrieved January 2012.
- "The Lagar Velho 1 Skeleton". Talk Origins. July 2000. Retrieved January 2012.; Sample, Ian (14 September 2006). "Life on the edge: was a Gibraltar cave last outpost of the lost neanderthal?". Retrieved January 2012.; Hawks, John (13 September 2006). "Not a lasting last for the Neandertals". Retrieved January 2012.
- Soficaru A, Dobos A, Trinkaus E (November 2006). "Early modern humans from the Peştera Muierii, Baia de Fier, Romania". Proceedings of the National Academy of Sciences 103 (46): 17196–201. Bibcode:2006PNAS..10317196S. doi:10.1073/pnas.0608443103. PMC 1859909. PMID 17085588.
- Jordan, Paul (January 2000). Neanderthal. Sutton Publishing. ISBN 0-7509-1934-5.
- Hayes, Jacqui (2 November 2006). "Humans and Neanderthals interbred". Cosmos. Retrieved 17 May 2009.
- Trinkaus E, Moldovan O, Milota S, Bîlgăr A, Sarcina L, Athreya S, Bailey SE, Rodrigo R, Mircea G, Higham T, Ramsey CB, van der Plicht J (September 2003). "An early modern human from the Peştera cu Oase, Romania". Proceedings of the National Academy of Sciences 100 (20): 11231–6. Bibcode:2003PNAS..10011231T. doi:10.1073/pnas.2035108100. PMC 208740. PMID 14504393.
- Trinkaus E (May 2007). "European early modern humans and the fate of the Neandertals". Proceedings of the National Academy of Sciences 104 (18): 7367–72. Bibcode:2007PNAS..104.7367T. doi:10.1073/pnas.0702214104. PMC 1863481. PMID 17452632.
- Washington University in St. Louis (8 December 2008). "Late Neandertals and Modern Human Contact in Southeastern Iberia". Newswise. Archived from the original on 22 May 2009. Retrieved 16 May 2009.
- Duarte C, Maurício J, Pettitt PB, Souto P, Trinkaus E, van der Plicht H, Zilhão J (June 1999). "The early Upper Paleolithic human skeleton from the Abrigo do Lagar Velho (Portugal) and modern-human emergence in Iberia". Proceedings of the National Academy of Sciences 96 (13): 7604–9. Bibcode:1999PNAS...96.7604D. doi:10.1073/pnas.96.13.7604. PMC 22133. PMID 10377462. Retrieved 17 May 2009.
- Ruzicka J, Hansen EH, Ghose AK, Mottola HA (February 1979). "Enzymatic determination of urea in serum based on pH measurement with the flow injection method". Analytical Chemistry 51 (2): 199–203. doi:10.1021/ac50038a011. PMID 33580.
- Rasmussen et al 2011 An Aboriginal Australian genome reveals separate human dispersals into Asia. Science. 2011 Oct 7;334(6052) 94-8. doi:10.1126/science.1211177
- Callaway, Ewen (September 22, 2011), First Aboriginal genome sequenced, Nature News, doi:10.1038/news.2011.551
- Reich et al. (2011), "Denisova Admixture and the First Modern Human Dispersals into Southeast Asia and Oceania", The American Journal of Human Genetics, doi:10.1016/j.ajhg.2011.09.005, PMC 3188841, PMID 21944045
- Choi, Charles (September 22, 2011), Now-Extinct Relative Had Sex with Humans Far and Wide, LiveScience
- Laurent Abi-Rached, et al. (2011-08-25). "The Shaping of Modern Human Immune Systems by Multiregional Admixture with Archaic Humans". Science 334 (6052). doi:10.1126/science.1209202. PMID 21868630. Archived from the original on Aug 2011. Lay summary.
- Human ancestors interbred with related species
- Hunter-gatherer genomes a trove of genetic diversity