Title of Presentation

“Ancient DNA – from humble beginnings to high-quality genomes”

The vast majority of species and populations that ever lived on our planet are extinct. From a small fraction of these, tissues still exist either in museum collections or as archaeological and paleontological remains. Over the past 30 years, I have worked on developing and employing methods to retrieve DNA from such remains.

When an organism dies, its DNA is rapidly degraded by enzymatic processes and over time other chemical processes continue to damage the DNA. Therefore, ancient DNA molecules are present in small amounts and are degraded to small pieces that are often chemically modified. In addition, the contamination of old specimens or reagents with miniscule amounts of contemporary DNA can easily lead to erroneous results. Over the years, we have learned to overcome some of these problems and have been able to retrieve DNA sequences from Pleistocene organisms such as cave bears, mammoths and Neandertals. We have also shown that DNA can survive in other ancient remains such as coprolites and ancient corn cobs from early farmers. Our particular focus has been the reconstruction of DNA sequences from extinct hominins in order to illuminate human evolution and determine the genetic features that make us human.

Our first draft version of the Neandertal genome in 2010, derived from three bones from Vindija Cave in Croatia, allowed us to show for the first time that Neandertals made a genetic contribution to humans living today. We subsequently completed a high-quality Neandertal genome and an additional high-quality genome from a tiny, unremarkable bone found in 2008 in Denisova Cave in the Altai Mountains. This genome turned out to be the first evidence for a hitherto unknown group of Asian hominins which were distantly related to Neandertals and are now called Denisovans.

Analyses of these genomes show that gene flow occurred among several different hominins in the late Pleistocene. In particular, Neandertals contributed about 2.0% of the genomes of people today living outside Africa while Denisovans contributed about 4.8% of the genomes of people living in Oceania and small amounts to people elsewhere in Asia. Work from several laboratories has shown that these genetic contributions have consequences today for the immune system, for lipid metabolism, for adaptation to life at high altitudes in the Himalayas, and for susceptibility to diseases such as diabetes. Further insights into our evolution are expected from our ongoing work to retrieve DNA from 400,000-year-old hominin fossils from Spain.

Profile

Web Site URL

http://www.eva.mpg.de/genetics/staff/paabo/

A brief Biography

By developing techniques approaches that allow DNA sequences from extinct creatures such as mammoths, ground sloths and Neandertals to be determined, Svante Pääbo founded the field of molecular palaeontology. He recently published a high-quality Neandertal genome sequence, allowing for the reconstruction of the origins and evolutionary history of our species. He discovered the Denisovans, a new hominin only known from a genome sequence retrieved from a small Siberian bone. Pääbo also works on the comparative genomics of humans and apes, particularly the evolution of genetic features that may underlie aspects of traits specific to humans such as the ‘speech and language’ gene FOXP2.

Svante Pääbo has received several honorary doctorates and scientific prizes and is a member of numerous academies. He is a founding Director at the Max-Planck Institute for Evolutionary Anthropology in Leipzig, Germany, and the author of the book “Neanderthal Man – In Search of Lost Genomes”.

Details of selected Awards and Honors

Honorary Doctorates

1994	University of Zurich, Switzerland.
2000	University of Helsinki, Finland.
2008	Royal Institute of Technology, Stockholm, Sweden.
2012	Karolinska Institute, Stockholm, Sweden.
2015	National University of Ireland, Galway.

Orders and Medals

2008	Order of Terra Mariana, 3rd Class, Republic of Estonia.
2009	Knight Commanders Cross (Bundesverdienstkreuz mit Stern), Germany.
2010	Theodor Bücher Medal, Federation of European Biochemical Societies.
2012	The King’s Medal (Kon:sGM12mhb), Stockholm, Sweden.
2015	Lomonosov Large Gold Medal, Russian Academy of Sciences, Moscow.

Prizes for Research Achievement

2005	Louis Jeantet Prize for Medicine, Geneva, Switzerland. (CHF 700,000)
2013	Gruber Genetics Prize, New Haven, CT, USA. (500,000 USD)

A list of selected Publications

1. Pääbo, S.: Molecular cloning of ancient Egyptian mummy DNA. Nature 314: 644-645 (1985).

2. Pääbo, S.: Ancient DNA; extraction, characterization, molecular cloning and enzymatic amplification. Proc. Natl. Acad. Sci. USA 86: 1939-1943 (1989).

3. Höss, M., Pääbo, S., and Vereshchagin, N.K.: Mammoth DNA sequences. Nature 370: 333 (1994).

4. Krings, M., Stone, A., Schmitz, R.W., Krainitzki, H., Stoneking, M., and Pääbo, S.: Neandertal DNA sequences and the origin of modern humans. Cell 90: 19-30 (1997).

5. Greenwood, A.D., Capelli, C., Possnert, G., and Pääbo, S.: Nuclear DNA sequences from Pleistocene megafauna. Mol. Biol. Evol. 16: 1466-1473 (1999).

6. Enard, W., Przeworski, M., Fisher, S.E., Lai, C.S.L., Wiebe, V., Kitano, T., Monaco, A.P.,and Pääbo, S.: Molecular evolution of FOXP2, a gene involved in speech and language. Nature418: 869-872 (2002).

7. Green, R.E., Malaspinas, A.-S., Krause, J., Briggs, A.W., Johnson, P.L.F., Uhler, C., Meyer, M., Good, J.M., Maricic, T., Stenzel, U., Prüfer, K., Siebauer, M., Burbano, H.A., Ronan, M., Rothberg, J.M., Egholm, M., Rudan, P., Brajković, D., Kućan, Ž., Gušić, I., Wikström, M., Laakkonen, L., Kelso, J., Slatkin, M., and Pääbo, S.: A complete Neandertal mitochondrial genome sequence determined by high-throughput sequencing. Cell 134: 416-426 (2008).

8. Briggs, A., J.M. Good, R.E. Green, J. Krause, T. Maricic, U. Stenzel, C. Lalueza-Fox, P. Rudan, D. Brajković, Ž. Kućan, I. Gušić, R. Schmitz, V.B. Doronichev, L.V.Golovanova, M. de la Rasilla, J. Fortea, A. Rosas and S. Pääbo: Targeted retrieval and analysis of five Neandertal mtDNA genomes. Science 325, 318-321 (2009).

9. Krause, J., Fu, Q., Good, J.M., Viola, B., Shunkov, M.V., Derevianko, A.P., and Pääbo, S.: The complete mtDNA genome of an unknown hominin from Southern Siberia. Nature 464: 894- 897 (2010).

10. Green, R.E., Krause, J., Briggs, A.W., Maricic, T., Stenzel, U., Kircher, M., Patterson, N., Li, H., Zhai, W., Fritz, M.H-Y., Hansen, N.F., Durand, E.Y., Malaspinas, A.-S., Jensen, J.D., Marques-Bonet, T., Alkan, C., Prufer, K., Meyer, M., Burbano, H.A., Good, J.M., Schultz, R., Aximu-Petri, A., Butthof, A., Hober, B., Hoffner, B., Siegemund, M., Weihmann, A., Nusbaum, C., Lander, E.S., Russ, C., Novod, N., Affourtit, J., Egholm, M., Verna, C., Rudan, P., Brajkovic, D., Kucan, Ž., Gušic, I., Doronichev, V.B., Golovanova, L.V., Lalueza-Fox, C., de la Rasilla, M., Fortea, J., Rosas, A., Schmitz, R.W., Johnson, P.L.F., Eichler, E.E., Falush, D., Birney, E., Mullikin, J.C., Slatkin, M., Nielsen, R., Kelso, J., Lachmann, M., Reich, D., and Pääbo, S.: A draft sequence of the Neandertal genome. Science 328: 710-22 (2010).

11. Reich, D., Green, R.E., Kircher, M., Krause, J., Patterson, N., Durand, E.Y., Viola, B., Briggs, A.W., Stenzel, U., Johnson, P.L.F., Maricic, T., Good, J.M., Marques-Bonet, T., Alkan, C., Fu, Q., Mallick, S., Li, H., Meyer, M., Eichler, E.E., Stoneking, M., Richards, M., Talamo, S., Shunkov, M.V., Derevianko, A.P., Hublin, J.-J., Kelso, J., Slatkin, M., and Pääbo, S.: Genetic history of an archaic hominin group from Denisova Cave in Siberia. Nature 468:1053-1060 (2010).

12. Meyer, M., Kircher, M., Gansauge, M.-T., Li, H., Racimo, F., Mallick, S., Schraiber, J.G.,Jay, F., Prüfer, K., de Filippo, C., Sudmant, C., Alkan, P.H., 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.,Andrés, A.M., Eichler, E.E., Slatkin, M., Reich, D., Kelso, J., and Pääbo, S.: A high coverage genome sequence from an archaic Denisovan individual. Science 338: 222-226 (2012).

13. Prüfer, K., Racimo, F., Patterson, N., Jay, F., Sankararaman, S., Sawyer, S., Heinze, A., Renaud, G., Sudmant, P.H., de Filippo, C., Li, H., Mallick, S., Dannemann, M., Fu, Q., Kircher, M., Kuhlwilm, M., Lachmann, M., Meyer, M., Ongyerth, M., Siebauer, M., Theunert, C., Tandon, A., Moorjani, P., Pickrell, J., Mullikin, J.C., Vohr, S.H., Green, R.E., Hellmann, I., Johnson, P.L.F., Blanche, H., Cann, H., Kitzman, J.O., Shendure, J., Eichler, E.E., Lein, E.S., Bakken, T.E., Golovanova, L.V., Doronichev, V.B., Shunkov, M.V., Derevianko, A.P., Viola, B., Slatkin, M., Reich, D., Kelso, J., and Pääbo, S.: The complete genome sequence of a Neandertal from the Altai Mountains. Nature 505: 43-49 (2014).

14. Meyer, M., Fu, Q., Aximu-Petri, A., Glocke, I., Nickel, B., Arsuaga, J.-L., Martínez, I., Gracia, A., Bermúdez de Castro, J.M., Carbonell, E., and Pääbo, S.: A mitochondrial genome sequence of a hominin from Sima de los Huesos. Nature 505: 403-406 (2014).

15. Fu, Q., Li, H., Moorjani, P., Jay, F., Slepchenko, S.M., Bondarev, A.A., Johnson, P.L.F., Aximu-Petri, A., Prüfer, K., Filippo, C. de, Meyer, M., Zwyns, N., Salazar-Garcia, D.C., Kuzmin, Y.V., Keates, S.G., Kosintsev, P.A., Razhev, D.I., Richards, M.P., Peristov, N.V., Lachmann, M., Douka, K., Higham, T.F.G., Slatkin, M., Hublin, J.-J., Reich, D., Kelso, J., Viola, T.B., and Pääbo, S.: Genome sequence of a 45,000-year-old modern human from western Siberia. Nature 514: 445-449 (2014).