Neanderthal genetics

Genetic studies on Neanderthal ancient DNA became possible in the late 1990s.[2] The Neanderthal genome project, established in 2006, presented the first fully sequenced Neanderthal genome in 2013.

Reconstruction of a Neanderthal woman.[1]

Since 2005, evidence for substantial admixture of Neanderthals DNA in modern populations has accumulated.[3]

The divergence time between the Neanderthal and modern human lineages is estimated at between 750,000 and 400,000 years ago. The more recent time depth has been suggested by Endicott et al. (2010)[4] and Rieux et al. (2014)[5] A significantly deeper time of separation, combined with repeated early admixture events, was calculated by Rogers et al. (2017).[6]

On July 3, 2020, a team reported finding that a major genetic risk factor of the Covid-19 virus was inherited from archaic Neanderthals 60,000 years ago.[7][8]

Genome sequencing
Main article: Neanderthal genome project

In July 2006, the Max Planck Institute for Evolutionary Anthropology and 454 Life Sciences announced that they would sequence the Neanderthal genome over the next two years. It was hoped the comparison would expand understanding of Neanderthals, as well as the evolution of humans and human brains.[9]

In 2008 Richard E. Green et al. from Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, published the full sequence of Neanderthal mitochondrial DNA (mtDNA) and suggested "Neanderthals had a long-term effective population size smaller than that of modern humans."[10] In the same publication, it was disclosed by Svante Pääbo that in the previous work at the Max Planck Institute, "Contamination was indeed an issue," and they eventually realised that 11% of their sample was modern human DNA.[11][12] Since then, more of the preparation work has been done in clean areas and 4-base pair 'tags' have been added to the DNA as soon as it is extracted so the Neanderthal DNA can be identified.

Geneticist at the Max Planck Institute for Evolutionary Anthropology extracting ancient DNA (2005 photograph)

The project first sequenced the entire genome of a Neanderthal in 2013 by extracting it from the phalanx bone of a 50,000-year-old Siberian Neanderthal.[13]

Among the genes shown to differ between present-day humans and Neanderthals were RPTN, SPAG17, CAN15, TTF1, and PCD16.[14]

A visualisation map of the reference modern-human containing the genome regions with high degree of similarity or with novelty according to a Neanderthal of 50 ka[13] has been built by Pratas et al.[15]

Interbreeding with modern humans
Main article: Neanderthal admixture

The question of possible interbreeding between Neanderthals and anatomically modern humans (AMH) had been looked into since the early archaeogenetic studies of the 1990s. In 2006, no evidence for interbreeding had yet been found.[16] In 2009, analysis of about one third of the full genome of the Altai individual was still reported as showing "no sign of admixture". The variant of microcephalin common outside Africa, which was suggested to be of Neanderthal origin and responsible for rapid brain growth in humans, was not found in Neanderthals. Nor was a very old MAPT variant which is found primarily in Europeans.[11]

Positive evidence for admixture was first published in May 2010.[14] Neanderthal-inherited genetic material is found in all non-African populations and was initially reported to comprise 1 to 4 percent of the genome.[14] This fraction was later refined to 1.5 to 2.1 percent.[13]

It is estimated that 20 percent of Neanderthal DNA currently survives in modern humans.[17] Modern human genes involved in making keratin, a protein constituent of skin, hair, and nails, have especially high levels of introgression. For example, approximately 66% of East Asians contain a POUF23L variant introgressed from Neanderthals, while 70% of Europeans possess an introgressed allele of BNC2. Neanderthal variants affect the risk of developing several diseases, including lupus, biliary cirrhosis, Crohn's disease, type 2 diabetes, and severe COVID-19.[17][7][8] The allele of MC1R which was originally linked to red hair in Neanderthals is not found in Europeans, but is present in Taiwanese Aborigines at a frequency of 70% and at moderately high frequencies in other East Asian populations; hence, there is actually no evidence that Neanderthals had red hair.[18] While interbreeding is viewed as the most parsimonious interpretation of these genetic findings, the 2010 study still could not conclusively rule out an alternative scenario, in which the source population of non-African modern humans was already more closely related to Neanderthals than other Africans were, because of ancient genetic divisions within Africa.[14][19]

Le Moustier Neanderthal skull reconstitution, Neues Museum Berlin[20]

Research since 2010 has refined the picture of interbreeding between Neanderthals, Denisovans and anatomically modern humans. Interbreeding appears to have occurred asymmetrically among the ancestors of modern-day humans, and that this is a possible rationale for differing frequencies of Neanderthal-specific DNA in the genomes of modern humans. In Vernot and Akey (2015) concluded that the relatively greater quantity of Neanderthal-specific DNA in the genomes of individuals of East Asian descent (than those of European descent) cannot be explained by differences in selection.[21] They further suggest that "two additional demographic models, involving either a second pulse of Neandertal gene flow into the ancestors of East Asians or a dilution of Neandertal lineages in Europeans by admixture with an unknown ancestral population" are parsimonious with their data.[21] Similar conclusions were reached by Kim and Lohmueller (2015): "It has been hypothesized that the greater proportion of Neandertal ancestry in East Asians than in Europeans is due to the fact that purifying selection is less effective at removing weakly deleterious Neandertal alleles from East Asian populations. Using simulations of a broad range of models of selection and demography, we have shown that this hypothesis cannot account for the higher proportion of Neandertal ancestry in East Asians than in Europeans. Instead, more complex demographic scenarios, most likely involving multiple pulses of Neandertal admixture, are required to explain the data."[22]

Khrameeva et al. (2014), a German-Russian-Chinese collaboration, compiled a consensus Neanderthal genome based on the genome of the Altai individual and of three Vindjia individuals. This was compared to a consensus chimpanzee genome as the outgroup and to the genome of eleven modern populations (three African, three East Asian, three European). Beyond confirming the significantly higher similarity to the Neanderthal genome in non-Africans than in Africans, the study also found a difference in the distribution of Neanderthal-derived sites between Europeans and East Asians, suggesting recent evolutionary pressures. Asian populations showed clustering in functional groups related to immune and haematopoietic pathways, while Europeans showed clustering in functional groups related to the lipid catabolic process.[23]

Evidence for AMH admixture to Neanderthals at roughly 100,000 years ago was presented by Kuhlwilm et al. (2016).[24]

There have been at least three episodes of interbreeding. The first would have occurred soon after some modern humans left Africa. The second would have occurred after the ancestral Melanesians had branched off—these people seem to have thereafter bred with Denisovans. The third would have involved Neanderthals and the ancestors of East Asians only.[25][26][27]

A 2016 study presented evidence that Neanderthal males might not have had viable male offspring with AMH females. This could explain why no modern man to date has been found with a Neanderthal Y chromosome.[28]

A 2018 study concluded that interbreeding between Neanderthals and modern humans led initially to the exposure of each species to unfamiliar viruses. Later on, the exchange of genes granted resistance to those viruses, too.[29]

On July 3, 2020, scientists reported finding that a major genetic risk factor of the Covid-19 virus was inherited from archaic Neanderthals 60,000 years ago.[7][8][30] It is estimated that 16% of Europeans and 50% of south Asians have the particular sequence on chromosome III, with 63% of Bangladeshis having these gene sequences. Africans, Middle Easterners and East Asians reported the presence of the chromosome in very negligible amounts. [31]


Epigenetics

Complete DNA methylation maps for Neanderthal and Denisovan individuals were reconstructed in 2014.[32] Differential activity of HOX cluster genes lie behind many of the anatomical differences between Neanderthals and modern humans, especially in regards to limb morphology. In general, Neanderthals possessed shorter limbs with curved bones.[32][33]

See also

References
  1. "Cro-Magnons Conquered Europe, but Left Neanderthals Alone". PLOS Biology. 2 (12): e449. 30 November 2004. doi:10.1371/journal.pbio.0020449. ISSN 1545-7885. PMC 532398.
  2. Ovchinnikov, Igor V.; Götherström, Anders; Romanova, Galina P.; Kharitonov, Vitaliy M.; Lidén, Kerstin; Goodwin, William (2000). "Molecular analysis of Neanderthal DNA from the northern Caucasus". Nature. 404 (6777): 490–93. Bibcode:2000Natur.404..490O. doi:10.1038/35006625. ISSN 0028-0836. PMID 10761915. S2CID 3101375.
  3. Sánchez-Quinto, F; Botigué, LR; Civit, S; Arenas, C; Avila-Arcos, MC; Bustamante, CD; Comas, D; Lalueza-Fox, C (October 17, 2012). "North African Populations Carry the Signature of Admixture with Neandertals". PLOS ONE. 7 (10): e47765. Bibcode:2012PLoSO...747765S. doi:10.1371/journal.pone.0047765. PMC 3474783. PMID 23082212. Fu, Q; Li, H; Moorjani, P; Jay, F; Slepchenko, SM; Bondarev, AA; Johnson, PL; Aximu-Petri, A; Prüfer, K; de Filippo, C; Meyer, M; Zwyns, N; Salazar-García, DC; Kuzmin, YV; Keates, SG; Kosintsev, PA; Razhev, DI; Richards, MP; Peristov, NV; Lachmann, M; Douka, K; Higham, TF; Slatkin, M; Hublin, JJ; Reich, D; Kelso, J; Viola, TB; Pääbo, S (October 23, 2014). "Genome sequence of a 45,000-year-old modern human from western Siberia". Nature. 514 (7523): 445–49. Bibcode:2014Natur.514..445F. doi:10.1038/nature13810. hdl:10550/42071. PMC 4753769. PMID 25341783. Brahic, Catherine. "Humanity's forgotten return to Africa revealed in DNA", The New Scientist (February 3, 2014).
  4. 410–440 ka P. Endicott; S.Y.W. Ho; C. Stringer (2010). "Using genetic evidence to evaluate four palaeoanthropological hypotheses for the timing of Neanderthal and modern human origins" (PDF). Journal of Human Evolution. 59 (1): 87–95. doi:10.1016/j.jhevol.2010.04.005. PMID 20510437. S2CID 223433.
  5. 295–498 ka. A. Rieux (2014). "Improved calibration of the human mitochondrial clock using ancient genomes". Molecular Biology and Evolution. 31 (10): 2780–92. doi:10.1093/molbev/msu222. PMC 4166928. PMID 25100861.
  6. Rogers, AR; Bohlender, RJ; Huff, CD (2017). "Early history of Neanderthals and Denisovans". Proc Natl Acad Sci U S A. 114 (37): 9859–9863. doi:10.1073/PNAS.1706426114. PMC 5604018. PMID 28784789.; see also: Jordana Cepelewicz, Genetics Spills Secrets From Neanderthals' Lost History, Quanta Magazine, 18 September 2017. "The dating of that schism between the Neanderthals and the Denisovans is surprising because previous research had pegged it as much more recent: a 2016 study, for instance, set it at only 450,000 years ago. An earlier separation means we should expect to find many more fossils of both eventually. It also changes the interpretation of some fossils that have been found. Take the large-brained hominid bones belonging to a species called Homo heidelbergensis, which lived in Europe and Asia around 600,000 years ago. Paleoanthropologists have disagreed about how they relate to other human groups, some positing they were ancestors of both modern humans and Neanderthals, others that they were a nonancestral species replaced by the Neanderthals, who spread across Europe."
  7. Zimmer, Carl (4 July 2020). "DNA Linked to Covid-19 Was Inherited From Neanderthals, Study Finds - The stretch of six genes seems to increase the risk of severe illness from the coronavirus". Retrieved 5 July 2020.
  8. Zeberg, Hugo; Paabo, Svante (July 3, 2020). "The major genetic risk factor for severe COVID-19 is inherited from Neandertals". bioRxiv. doi:10.1101/2020.07.03.186296. hdl:21.11116/0000-0006-AB4F-2. S2CID 220366134. Retrieved 5 July 2020.
  9. Moulson, Geir; Associated Press (July 20, 2006). "Neanderthal genome project launches". NBC News. Retrieved August 22, 2006.
  10. Green, RE; Malaspinas, AS; Krause, J; Briggs, Aw; Johnson, PL; Uhler, C; Meyer, M; Good, JM; Maricic, T; Stenzel, U; Prüfer, K; Siebauer, M; Burbano, HA; Ronan, M; Rothberg, JM; Egholm, M; Rudan, P; Brajković, D; Kućan, Z; Gusić, I; Wikström, M; Laakkonen, L; Kelso, J; Slatkin, M; Pääbo, S (2008). "A complete Neandertal mitochondrial genome sequence determined by high-throughput sequencing". Cell. 134 (3): 416–26. doi:10.1016/j.cell.2008.06.021. PMC 2602844. PMID 18692465.
  11. Elizabeth Pennisi (2009). "Tales of a Prehistoric Human Genome". Science. 323 (5916): 866–71. doi:10.1126/science.323.5916.866. PMID 19213888. S2CID 206584252.
  12. Green RE, Briggs AW, Krause J, Prüfer K, Burbano HA, Siebauer M, Lachmann M, Pääbo S (2009). "The Neandertal genome and ancient DNA authenticity". EMBO J. 28 (17): 2494–502. doi:10.1038/emboj.2009.222. PMC 2725275. PMID 19661919.
  13. K. Prüfer; et al. (2014). "The complete genome sequence of a Neanderthal from the Altai Mountains". Nature. 505 (7481): 43–49. Bibcode:2014Natur.505...43P. doi:10.1038/nature12886. PMC 4031459. PMID 24352235.
  14. Green, Richard E.; Krause, Johannes; Briggs, Adrian W.; Maricic, Tomislav; Stenzel, Udo; Kircher, Martin; Patterson, Nick; Li, Heng; Zhai, Weiwei; Fritz, Markus Hsi-Yang; Hansen, Nancy F.; Durand, Eric Y.; Malaspinas, Anna-Sapfo; Jensen, Jeffrey D.; Marques-Bonet, Tomas; Alkan, Can; Prüfer, Kay; Meyer, Matthias; Burbano, Hernán A.; Good, Jeffrey M.; Schultz, Rigo; Aximu-Petri, Ayinuer; Butthof, Anne; Höber, Barbara; Höffner, Barbara; Siegemund, Madlen; Weihmann, Antje; Nusbaum, Chad; Lander, Eric S.; Russ, Carsten (2010). "A Draft Sequence of the Neandertal Genome". Science. 328 (5979): 710–22. Bibcode:2010Sci...328..710G. doi:10.1126/science.1188021. PMC 5100745. PMID 20448178.
  15. Pratas, D; Hosseini, M; Silva, R; Pinho, A; Ferreira, P (June 20–23, 2017). Visualization of Distinct DNA Regions of the Modern Human Relatively to a Neanderthal Genome. Iberian Conference on Pattern Recognition and Image Analysis. Springer. Lecture Notes in Computer Science. 10255. pp. 235–42. doi:10.1007/978-3-319-58838-4_26. ISBN 978-3-319-58837-7.
  16. "Neanderthal Genome Sequencing Yields Surprising Results And Opens A New Door To Future Studies" (Press release). Lawrence Berkeley National Laboratory. November 16, 2006. Retrieved May 31, 2009.
  17. "Surprise! 20 Percent of Neanderthal Genome Lives On in Modern Humans, Scientists Find". National Geographic. Retrieved October 7, 2016.
  18. Ding, Q (August 31, 2014). "Neanderthal origin of the haplotypes carrying the functional variant Val92Met in the MC1R in modern humans". Molecular Biology and Evolution. 31 (8): 1994–2003. doi:10.1093/molbev/msu180. PMID 24916031.
  19. Lowery, Robert K.; Uribe, Gabriel; Jimenez, Eric B.; Weiss, Mark A.; Herrera, Kristian J.; Regueiro, Maria; Herrera, Rene J. (2013). "Neanderthal and Denisova genetic affinities with contemporary humans: Introgression versus common ancestral polymorphisms". Gene. 530 (1): 83–94. doi:10.1016/j.gene.2013.06.005. ISSN 0378-1119. PMID 23872234.
  20. Bekker, Henk (23 October 2017). "Neues Museum in Berlin 1175".
  21. Vernot, Benjamin; Akey, Joshua M (2015). "Complex History of Admixture between Modern Humans and Neandertals". American Journal of Human Genetics. 96 (3): 454–61. doi:10.1016/j.ajhg.2015.01.006. PMC 4375686. PMID 25683119.
  22. Kim, BY; Lohmueller, KE (2015). "Selection and Reduced Population Size Cannot Explain Higher Amounts of Neandertal Ancestry in East Asian than in European Human Populations". American Journal of Human Genetics. 96 (3): 448–53. doi:10.1016/j.ajhg.2014.12.029. PMC 4375557. PMID 25683122.
  23. "Specifically, genes in the LCP [lipid catabolic process] term had the greatest excess of NLS in populations of European descent, with an average NLS frequency of 20.8±2.6% versus 5.9±0.08% genome wide (two-sided t-test, P<0.0001, n=379 Europeans and n=246 Africans). Further, among examined out-of-Africa human populations, the excess of NLS [Neanderthal-like genomic sites] in LCP genes was only observed in individuals of European descent: the average NLS frequency in Asians is 6.7±0.7% in LCP genes versus 6.2±0.06% genome wide." Khrameeva, Ekaterina E.; Bozek, Katarzyna; He, Liu; Yan, Zheng; Jiang, Xi; Wei, Yuning; Tang, Kun; Gelfand, Mikhail S.; Prufer, Kay; Kelso, Janet; Paabo, Svante; Giavalisco, Patrick; Lachmann, Michael; Khaitovich, Philipp (2014). "Neanderthal ancestry drives evolution of lipid catabolism in contemporary Europeans". Nature Communications. 5: 3584. Bibcode:2014NatCo...5.3584K. doi:10.1038/ncomms4584. PMC 3988804. PMID 24690587..
  24. Kuhlwilm, Martin; Gronau, Ilan; Hubisz, Melissa J.; de Filippo, Cesare; Prado-Martinez, Javier; Kircher, Martin; Fu, Qiaomei; Burbano, Hernán A.; Lalueza-Fox, Carles; Marco; Rosas, Antonio; Rudan, Pavao; Brajkovic, Dejana; Kucan, Željko; Gušic, Ivan; Marques-Bonet, Tomas; Andrés, Aida M.; Viola, Bence; Pääbo, Svante; Meyer, Matthias; Siepel, Adam; Castellano, Sergi (2016). "Ancient gene flow from early modern humans into Eastern Neanderthals". Nature. 530 (7591): 429–33. Bibcode:2016Natur.530..429K. doi:10.1038/nature16544. PMC 4933530. PMID 26886800.
  25. S. Sankararaman; S. Mallick; M. Dannemann; K. Prüfer; J. Kelso; N. Patterson; D. Reich (2014). "The landscape of Neandertal ancestry in present-day humans". Nature. 507 (7492): 354–57. Bibcode:2014Natur.507..354S. doi:10.1038/nature12961. PMC 4072735. PMID 24476815.
  26. Sankararaman, Sriram; Mallick, Swapan; Patterson, Nick; Reich, David (2016). "The Combined Landscape of Denisovan and Neanderthal Ancestry in Present-Day Humans". Current Biology. 26 (9): 1241–47. doi:10.1016/j.cub.2016.03.037. ISSN 0960-9822. PMC 4864120. PMID 27032491.
  27. "Neanderthals mated with modern humans much earlier than previously thought, study finds: First genetic evidence of modern human DNA in a Neanderthal individual". ScienceDaily. February 17, 2016. Retrieved March 6, 2016.
  28. Mendez, Fernando L.; et al. (April 7, 2016). "The Divergence of Neandertal and Modern Human Y Chromosomes" (PDF). The American Journal of Human Genetics. 98 (4): 728–34. doi:10.1016/j.ajhg.2016.02.023. PMC 4833433. PMID 27058445. Retrieved April 12, 2016.
  29. Enard, David; Petrov, Dmitri A. (October 4, 2018). "Evidence that RNA Viruses Drove Adaptive Introgression between Neanderthals and Modern Humans". Cell. 175 (2): 360–371. doi:10.1016/j.cell.2018.08.034. PMC 6176737. PMID 30290142.
  30. "Neanderthal genes may be liability for Covid19 patients". Fairfax_AP. 1 October 2020.
  31. Sample, Ian (30 September 2020). "Neanderthal genes increase risk of serious Covid-19, study claims". The Guardian. ISSN 0261-3077. Retrieved 30 September 2020.
  32. Gokhman D, Lavi E, Prüfer K, Fraga MF, Riancho JA, Kelso J, Pääbo S, Meshorer E, Carmel L (2014). "Reconstructing the DNA methylation maps of the Neandertal and the Denisovan". Science. 344 (6183): 523–27. Bibcode:2014Sci...344..523G. doi:10.1126/science.1250368. PMID 24786081. S2CID 28665590.
  33. Tibayrenc, Michel; Ayala, Francisco J. (2016-09-12). On Human Nature: Biology, Psychology, Ethics, Politics, and Religion. ISBN 9780127999159.
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.