The information below refers to the time of the award.
Svante Pääbo is an honorary professor of genetics and evolutionary biology. He is the director of the Max-Planck-Institute for Evolutionary Anthropology in Leipzig. Svante Pääbo is a Swedish citizen. He was born in 1955.
Svante Pääbo is a pioneer in the study of ancient DNA. He has developed techniques that make the retrieval of DNA from museum specimens and archaeological remains possible and instituted controls that set standards in this field. More recently, he has focused on comparative evolutionary studies of primate genomes. His work aims at the discovery of specific genetic changes that took place in the recent human evolution when our species acquired phenotypic traits that set it apart from our closest relative, the chimpanzee. By comparing the human genome and its functional expression to that of other primates, it has become feasible to identify changes that were fixed in the genome by positive selection and may thus have conferred an advantage to human ancestors. Understanding the genetics of such traits does not only broaden our fundamental knowledge about evolution and human biology, it also may contribute to explain the basis of diseases that affect traits specific to humans, for example speech or cognitive abilities.
With the Louis-Jeantet Prize for medicine, Svante Pääbo wants to study the function of genes that show differences between humans and apes and that were positively selected in human evolution. One of these genes, FOXP2, is involved in speech and language development. To this end he will create transgenic mice that carry either the human or chimpanzee version of the gene. Svante Pääbo plans to recruit to his project two new collaborators.
Svante Pääbo studied egyptology and history of science as well as medicine at the University of Uppsala. In 1986, he obtained his PhD in Medical Sciences at the same university. After his postdoctoral research at the Universities of Zurich and of California at Berkeley, he became, in 1990, Full Professor of General Biology at the University of Munich. He is presently the Director of the Max-Planck Institute for Evolutionary Anthropology in Leipzig. He is Honorary Professor of Genetics and Evolutionary Biology at the University of Leipzig and Guest Professor of Comparative Genomics at the University of Uppsala. He is a member of several academies including the Royal Swedish Academy of Sciences, the National Academy of Sciences of the USA, and the Leopoldina. He holds honorary degrees from the Universities of Zurich and Helsinki.
The Genetics of Being Human
The goal of Svante Pääbo’s research is to better understand human evolutionary history through genetic analyses. To do this, he uses several different approaches, many of which he has personally been involved in developing. In doing this, he has partly been helped by the unusual combination of subjects he studied as an undergraduate. When he subsequently became a graduate student in medical genetics in the early 80s he started to combine these areas and used the then novel techniques of DNA cloning to isolate DNA from ancient Egyptian mummies. Together with the late Allan Wilson at UC Berkeley, who independently pursued similar goals, he thus founded the field of molecular archaeology, the study of DNA from archaeological and paleontological remains. Since then, he has been responsible for the development of almost all techniques that are currently used to isolate and study ancient DNA. This is not a small task since such DNA is highly degraded and modified by hydrolytic and oxidative processes that may cause mistakes during its isolation by replication. In addition, ancient tissues often contain modern DNA that may confuse analyses. The methods and controls he has pioneered to tackle these problems are today the international standard in this field and have been used to study the genetics of long-since extinct animals such as mammoths, ground sloths, and cave bears. The techniques of ancient DNA analysis have also been applied to thousands of biological specimens in museum collections as well as to forensic investigations.
A highlight of this work was Svante Pääbo’s recovery of DNA sequences from Neandertals and the demonstration that the Neandertals did not contribute mitochondrial DNA to the contemporary human gene pool. Instead, they shared a mitochondrial DNA ancestor with humans more than 500’000 years ago. Although these results have sometimes been over-interpreted to exclude all possibility of a genetic contribution of Neandertals to anatomically modern humans, Svante Pääbo has emphasized a balanced interpretation that put the results in the context of population genetics. Recently, Svante Pääbo and his colleagues have surveyed several Neandertal specimens and used a population genetic model to show that the genetic contribution of Neandertals to modern humans may have been small, but could have been as large as 25% (Figure 1).
Figure 1: Neandertals have disappeared about 30’000 years ago. Mitochondrial DNA sequences recovered from Neandertal bones were compared to mitochondrial DNA sequences of modern humans. The results indicate that the genetic contribution of Neandertals to modern humans may have been small and could not have been larger than 25%.
Svante Pääbo has also championed genome comparisons between living humans and the great apes as a means to better understand the genetic background to human uniqueness. His studies of the genetic variation among humans and apes have shown that humans differ from the great apes in having a lower genetic variation in their nuclear genome. He has pioneered a functional genomic approach to human evolution by comparing gene activity of humans and apes. He has shown that whereas the genomes of humans and chimpanzees differ by a mere 1.2%, about 10% of genes differ significantly in expression between the two species. He has recently suggested that most of these expression changes are of little or no functional consequence and that this can be used to identify, with statistical confidence, the few genes that have changed their expression due to positive selection for new functions uniquely important in human evolution. He has also shown that both expression changes and amino acid sequence changes have been more frequent on the human evolutionary lineage than on the chimpanzee lineage among genes expressed in the brain than among gene expressed in four other tissues. This opens the way to identifying changes in genes that may have been crucial for the foundation of the unique cognitive abilities of humans. It may also become important for the future understanding of diseases that affect traits unique to humans and are therefore impossible to study in animal models.
One example of such a genetic change was found by Svante Pääbo in the gene FOXP2, which when destroyed by mutations, causes severe language and speech problems in humans. He showed that this gene has experienced two amino acid changes on the human lineage and that the pattern of polymorphisms around these amino acid changes indicates that they were the targets of strong positive selection during human evolution (Figure 2).
Figure 2: In humans, the FOXP2 gene is needed for language. Comparison of its sequence to those of other primate species indicates a recent rapid evolution in the human lineage represented by mutations in two amino acids and surrounding sequences. These changes were fixed in the human population at a time-point that could be compatible with the appearance of articulate language.
By dating of this selective sweep, he showed that it is likely to have reached fixation among humans during the last 250’000 years, i.e. substantially later than the divergence between anatomically modern humans and Neandertals. This suggests that articulate language was a trait distinguishing modern humans and archaic humans. In his current work he attempts to show what abilities this and other genes conferred on human ancestors.