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The Predecessors Within . . .
Leading Edge
Previews The Predecessors Within . . . Benjamin Vernot1,* and Svante Pa¨a¨bo1,* 1Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, D-04103 Leipzig, Germany *Correspondence: [email protected] (B.V.), [email protected] (S.P.) https://doi.org/10.1016/j.cell.2018.03.023
By examining the genomes of present-day people from Asia, researchers show that modern humans met and interbred with Denisovans, distant relatives to Neanderthals, on at least two occasions. As a result, people today carry DNA from two different Denisovan populations. Neanderthals existed for almost half a million years in Europe and western Asia and disappeared some 40,000 years ago, at about the time when modern humans spread in large numbers outside Africa and the Near East. Ever since Neanderthals were first recognized as a separate hominin group more than 100 years ago, their history and relationship to modern humans have been sources of fascination and debate. Opinions have ranged from Neanderthals being the direct ancestors of present-day Europeans to having become completely extinct when modern humans established themselves across Eurasia. For decades, these questions have been debated by archaeologists and paleontologists. Lately, molecular genetics has mixed into this debate and provided some answers. In this issue of Cell, Browning et al. take a closer look at how DNA sequences in the genomes of people in Asia relate to the Denisovan and Neanderthal genomes, lending insight into the interactions of these groups with modern humans (Browning et al., 2018). With the availability of the first draft Neanderthal genome sequence in 2010 (Green et al., 2010), it became clear that Neanderthals had not become fully extinct. On the order of 2% of the genomes of present-day people whose genetic roots are outside sub-Saharan Africa stems from Neanderthals. This shows that when the two groups met, they at least sometimes had children together, and some of these children became so successfully integrated in modern human societies that they in turn generated offspring and contributed to future generations. As a result, humans today often carry thousands of genetic variants of Neanderthal origin.
Our understanding of our hominin relatives took a further leap forward when the genome of a tiny bone from a cave in the Altai Mountains in southern Siberia was sequenced in 2010 and turned out to come from a hominin group that separated from Neanderthals more than 400,000 years ago (Reich et al., 2010). This group was named ‘‘Denisovans’’ after the cave where the bone was found. Although their remains have so far been found only in Siberia, there is good reason to believe that Denisovans were once widespread in Asia as people in most parts of Asia carry small amounts of Denisovan DNA, with people in Oceania carrying as much as 5%–6% (Reich et al., 2010). Denisovan DNA in humans today is thus less homogenously distributed than that of Neanderthals, indicating that their interactions with ancestors of modern-day people may have been more complex. In this issue, Browning et al. provide insights into these interactions. The authors find that DNA sequences inherited from Denisovans can be divided into two components: those that are closely related to the sequenced Denisovan genome and those that are more distantly related to the Denisovan genome. The component that is more diverged from the Denisovan genome occurs in Papua New Guineans and other people in Oceania, as well as in smaller amounts in almost all Asian populations. In contrast, the Denisovan component that is more closely related to the sequenced Denisovan genome occurs in China and Japan and makes up about a third of the total Denisovan DNA in these populations. These observations provide evidence that two different Denisovan populations interbred with modern humans on different occasions (Figure 1).
6 Cell 173, March 22, 2018 ª 2018 Elsevier Inc.
Interestingly, when Browning et al. look at the Neanderthal component in Asia and Europe, it seems homogeneous, suggesting that it could have come from a single Neanderthal population. It has been previously shown that people in Asia carry somewhat more Neanderthal DNA than people in Europe (Wall et al., 2013), and this has been interpreted either as evidence of additional mixing between Neanderthals and the ancestors of Asians or ‘‘dilution’’ of the Neanderthal component in Europe by mixture with a modern human population that carried little or no Neanderthal DNA (Lazaridis et al., 2016; Vernot and Akey, 2015). Although the analysis of Browning et al. provides no evidence for more than one Neanderthal population contributing to present-day people, these scenarios may be difficult to disentangle if the Neanderthals that interacted with modern humans were so homogeneous that different populations cannot be distinguished from their DNA remnants in people today. The methods used by Browning et al. to identify archaic DNA in present-day human genomes operate in their first steps without considering an archaic reference genome. For example, in Oceanians they first identify a number of putatively archaic haplotypes and later categorize these as Denisovan or Neanderthal by comparing them with ancient genomes. This approach is exciting as it could allow for the identification of DNA from archaic hominins whose genomes have not yet been recovered. Although this manuscript describes an important step forward in improving such reference-free methods, approximately 25% of the haplotypes they identified do not match either Denisovans or Neanderthals. At this point, we have no way of knowing whether these derive from an as-yet-unknown archaic
that this individual had a Neanderthal relative some four to six generations back in his genealogy (Fu et al., 2015). Hopefully, future discoveries of ancient Asian specimens with such recent admixture, as well as advances in computational methods like those in Browning et al., will shed more light on where and when Denisovans mixed with other groups.
REFERENCES Green, R.E., Krause, J., Briggs, A.W., Maricic, T., Stenzel, U., Kircher, M., Patterson, N., Li, H., Zhai, W., Fritz, M.H.Y., et al. (2010). A draft sequence of the Neandertal genome. Science 328, 710–722. 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., et al. (2010). Genetic history of an archaic hominin group from Denisova Cave in Siberia. Nature 468, 1053–1060. Browning, S.R., Browning, B.L., Zhou, Y., Tucci, S., and Akey, J.M. (2018). Analysis of human sequence data reveals two pulses of archaic Denisovan admixture. Cell 173, this issue, 53–61.
Figure 1. Interactions between Archaic Hominins and Modern Humans Top: Relationships between archaic hominins and modern humans. Arrows show the minimum number of interbreedings between Denisovan, Neanderthal, and modern human populations necessary to produce the results in Browning et al. The dark blue arrow from Denisovans to East Asians is newly presented in this work. We note that additional genetic interactions between and among archaics and modern humans are possible, and even likely, and that much of the timing and details of the illustrated interactions are still unknown. Bottom: Map showing locations of Neanderthal and Denisovan bones with sequenced genomes (green dots, Neanderthals; blue dot, Denisovan) and rough ranges of DNA contributions from these groups in humans today (Sankararaman et al., 2016).
group or are simply false positives. Ideally, future methods will be developed to extract information from such sequences. In the meantime, we are hopeful that additional genome sequences from archaic hominins will provide direct evidence for which groups were present when modern humans emerged and spread around the globe.
As more and more ancient genomes are sequenced, there is also hope that direct evidence for mixing between groups may be forthcoming. A first indication of this is the genome of a 40,000-year-old modern mandible found in 2002 in Romania, which turned out to carry seven large chromosomal regions of Neanderthal origin, showing
Wall, J.D., Yang, M.A., Jay, F., Kim, S.K., Durand, E.Y., Stevison, L.S., Gignoux, C., Woerner, A., Hammer, M.F., and Slatkin, M. (2013). Higher levels of neanderthal ancestry in East Asians than in Europeans. Genetics 194, 199–209. Lazaridis, I., Nadel, D., Rollefson, G., Merrett, D.C., Rohland, N., Mallick, S., Fernandes, D., Novak, M., Gamarra, B., Sirak, K., et al. (2016). Genomic insights into the origin of farming in the ancient Near East. Nature 536, 419–424. Vernot, B., and Akey, J.M. (2015). Complex history of admixture between modern humans and Neandertals. Am. J. Hum. Genet. 96, 448–453. Fu, Q., Hajdinjak, M., Moldovan, O.T., Constantin, S., Mallick, S., Skoglund, P., Patterson, N., Rohland, N., Lazaridis, I., Nickel, B., et al. (2015). An early modern human from Romania with a recent Neanderthal ancestor. Nature 524, 216–219. Sankararaman, S., Mallick, S., Patterson, N., and Reich, D. (2016). The combined landscape of Denisovan and Neanderthal ancestry in present-day humans. Curr. Biol. 26, 1241–1247.
Cell 173, March 22, 2018 7
Previews The Predecessors Within . . . Benjamin Vernot1,* and Svante Pa¨a¨bo1,* 1Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, D-04103 Leipzig, Germany *Correspondence: [email protected] (B.V.), [email protected] (S.P.) https://doi.org/10.1016/j.cell.2018.03.023
By examining the genomes of present-day people from Asia, researchers show that modern humans met and interbred with Denisovans, distant relatives to Neanderthals, on at least two occasions. As a result, people today carry DNA from two different Denisovan populations. Neanderthals existed for almost half a million years in Europe and western Asia and disappeared some 40,000 years ago, at about the time when modern humans spread in large numbers outside Africa and the Near East. Ever since Neanderthals were first recognized as a separate hominin group more than 100 years ago, their history and relationship to modern humans have been sources of fascination and debate. Opinions have ranged from Neanderthals being the direct ancestors of present-day Europeans to having become completely extinct when modern humans established themselves across Eurasia. For decades, these questions have been debated by archaeologists and paleontologists. Lately, molecular genetics has mixed into this debate and provided some answers. In this issue of Cell, Browning et al. take a closer look at how DNA sequences in the genomes of people in Asia relate to the Denisovan and Neanderthal genomes, lending insight into the interactions of these groups with modern humans (Browning et al., 2018). With the availability of the first draft Neanderthal genome sequence in 2010 (Green et al., 2010), it became clear that Neanderthals had not become fully extinct. On the order of 2% of the genomes of present-day people whose genetic roots are outside sub-Saharan Africa stems from Neanderthals. This shows that when the two groups met, they at least sometimes had children together, and some of these children became so successfully integrated in modern human societies that they in turn generated offspring and contributed to future generations. As a result, humans today often carry thousands of genetic variants of Neanderthal origin.
Our understanding of our hominin relatives took a further leap forward when the genome of a tiny bone from a cave in the Altai Mountains in southern Siberia was sequenced in 2010 and turned out to come from a hominin group that separated from Neanderthals more than 400,000 years ago (Reich et al., 2010). This group was named ‘‘Denisovans’’ after the cave where the bone was found. Although their remains have so far been found only in Siberia, there is good reason to believe that Denisovans were once widespread in Asia as people in most parts of Asia carry small amounts of Denisovan DNA, with people in Oceania carrying as much as 5%–6% (Reich et al., 2010). Denisovan DNA in humans today is thus less homogenously distributed than that of Neanderthals, indicating that their interactions with ancestors of modern-day people may have been more complex. In this issue, Browning et al. provide insights into these interactions. The authors find that DNA sequences inherited from Denisovans can be divided into two components: those that are closely related to the sequenced Denisovan genome and those that are more distantly related to the Denisovan genome. The component that is more diverged from the Denisovan genome occurs in Papua New Guineans and other people in Oceania, as well as in smaller amounts in almost all Asian populations. In contrast, the Denisovan component that is more closely related to the sequenced Denisovan genome occurs in China and Japan and makes up about a third of the total Denisovan DNA in these populations. These observations provide evidence that two different Denisovan populations interbred with modern humans on different occasions (Figure 1).
6 Cell 173, March 22, 2018 ª 2018 Elsevier Inc.
Interestingly, when Browning et al. look at the Neanderthal component in Asia and Europe, it seems homogeneous, suggesting that it could have come from a single Neanderthal population. It has been previously shown that people in Asia carry somewhat more Neanderthal DNA than people in Europe (Wall et al., 2013), and this has been interpreted either as evidence of additional mixing between Neanderthals and the ancestors of Asians or ‘‘dilution’’ of the Neanderthal component in Europe by mixture with a modern human population that carried little or no Neanderthal DNA (Lazaridis et al., 2016; Vernot and Akey, 2015). Although the analysis of Browning et al. provides no evidence for more than one Neanderthal population contributing to present-day people, these scenarios may be difficult to disentangle if the Neanderthals that interacted with modern humans were so homogeneous that different populations cannot be distinguished from their DNA remnants in people today. The methods used by Browning et al. to identify archaic DNA in present-day human genomes operate in their first steps without considering an archaic reference genome. For example, in Oceanians they first identify a number of putatively archaic haplotypes and later categorize these as Denisovan or Neanderthal by comparing them with ancient genomes. This approach is exciting as it could allow for the identification of DNA from archaic hominins whose genomes have not yet been recovered. Although this manuscript describes an important step forward in improving such reference-free methods, approximately 25% of the haplotypes they identified do not match either Denisovans or Neanderthals. At this point, we have no way of knowing whether these derive from an as-yet-unknown archaic
that this individual had a Neanderthal relative some four to six generations back in his genealogy (Fu et al., 2015). Hopefully, future discoveries of ancient Asian specimens with such recent admixture, as well as advances in computational methods like those in Browning et al., will shed more light on where and when Denisovans mixed with other groups.
REFERENCES Green, R.E., Krause, J., Briggs, A.W., Maricic, T., Stenzel, U., Kircher, M., Patterson, N., Li, H., Zhai, W., Fritz, M.H.Y., et al. (2010). A draft sequence of the Neandertal genome. Science 328, 710–722. 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., et al. (2010). Genetic history of an archaic hominin group from Denisova Cave in Siberia. Nature 468, 1053–1060. Browning, S.R., Browning, B.L., Zhou, Y., Tucci, S., and Akey, J.M. (2018). Analysis of human sequence data reveals two pulses of archaic Denisovan admixture. Cell 173, this issue, 53–61.
Figure 1. Interactions between Archaic Hominins and Modern Humans Top: Relationships between archaic hominins and modern humans. Arrows show the minimum number of interbreedings between Denisovan, Neanderthal, and modern human populations necessary to produce the results in Browning et al. The dark blue arrow from Denisovans to East Asians is newly presented in this work. We note that additional genetic interactions between and among archaics and modern humans are possible, and even likely, and that much of the timing and details of the illustrated interactions are still unknown. Bottom: Map showing locations of Neanderthal and Denisovan bones with sequenced genomes (green dots, Neanderthals; blue dot, Denisovan) and rough ranges of DNA contributions from these groups in humans today (Sankararaman et al., 2016).
group or are simply false positives. Ideally, future methods will be developed to extract information from such sequences. In the meantime, we are hopeful that additional genome sequences from archaic hominins will provide direct evidence for which groups were present when modern humans emerged and spread around the globe.
As more and more ancient genomes are sequenced, there is also hope that direct evidence for mixing between groups may be forthcoming. A first indication of this is the genome of a 40,000-year-old modern mandible found in 2002 in Romania, which turned out to carry seven large chromosomal regions of Neanderthal origin, showing
Wall, J.D., Yang, M.A., Jay, F., Kim, S.K., Durand, E.Y., Stevison, L.S., Gignoux, C., Woerner, A., Hammer, M.F., and Slatkin, M. (2013). Higher levels of neanderthal ancestry in East Asians than in Europeans. Genetics 194, 199–209. Lazaridis, I., Nadel, D., Rollefson, G., Merrett, D.C., Rohland, N., Mallick, S., Fernandes, D., Novak, M., Gamarra, B., Sirak, K., et al. (2016). Genomic insights into the origin of farming in the ancient Near East. Nature 536, 419–424. Vernot, B., and Akey, J.M. (2015). Complex history of admixture between modern humans and Neandertals. Am. J. Hum. Genet. 96, 448–453. Fu, Q., Hajdinjak, M., Moldovan, O.T., Constantin, S., Mallick, S., Skoglund, P., Patterson, N., Rohland, N., Lazaridis, I., Nickel, B., et al. (2015). An early modern human from Romania with a recent Neanderthal ancestor. Nature 524, 216–219. Sankararaman, S., Mallick, S., Patterson, N., and Reich, D. (2016). The combined landscape of Denisovan and Neanderthal ancestry in present-day humans. Curr. Biol. 26, 1241–1247.
Cell 173, March 22, 2018 7