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Svante Pääbo


In Search of Lost Genomes

Book review by Anthony Campbell. The review is licensed under a Creative Commons Licence.
Pääbo is famous for having shown that modern humans outside Africa interbred with the Neanderthals. Here he tells the story of how this discovery came about. Although the book is primarily an account of this work, it is also partly autobiographical and includes some excursions into the author's personal and emotional life. I am not sure we really needed these.

Pääbo first trained as a doctor in Sweden at the University of Uppsala and enjoyed seeing patients, but his primary interest was always in research, and after completing a PhD he joined a laboratory where he studied the DNA of Egyptian mummies. Some years later, after working at centres in a number of countries, he was unexpectedly offered a full professorship to set up a laboratory at the University of Munich.

Research in ancient DNA faces two major problems. How long can DNA survive,after death, and how much has it been contaminated after death? Research of the kind that Pääbo was interested in was possible only thanks to the technique of polymerase chain replication (PCR), discovered in 1983. This enables huge amounts of DNA to be replicated from a single fragment of the original molecule, but its very sensitivity poses a problem: any contaminating DNA will also be replicated. At Munich Pääbo became obsessive ("paranoid") in his quest to eliminate contamination. He is critical of claims, which still attract publicity, to have recovered DNA from specimens many millions of years old; he believes these are invariably spurious. In one instance he was able to prove this, but often the facts are impossible to establish.

Initially at Munich Pääbo concentrated on non-human research, thinking that to work on Neanderthals would be too difficult. But when he was offered the chance to study a sample from the original Neanderthal specimen discovered in the Neander valley he was unable to resist, and he did succeed in identifying mitochondrial DNA from this in 1997. But to isolate nuclear DNA would be much harder.

Another career move then ensued: Pääbo was invited to become director of the Department of Genetics at the Max Planck Institute for Evolutionary Anthroplogy in Leipzig. New techniques were becoming available and Pääbo applied these, first to DNA from mammoths and cave bears, and then to Neanderthal DNA. He succeeded in isolating fragments of nuclear DNA from the Neanderthal material.

In 2006, after a meeting at Cold Spring Harbor on Long Island, Pääbo made the admittedly rash announcement that he and his team would reconstruct the whole Neanderthal genome. The intensive research that ensued is described in some detail. The team published a draft sequence of the genome in 2010 and said that there was evidence for admixture of archaic and modern non-African humans.

Following his work on the Neanderthals, Pääbo applied his knowledge and expertise to studying a fragment of finger bone found in the Denisova Cave in the Altai region of Siberia. Mitochondrial analysis indicated that this individual belonged to a species that had branched off the human evolutionary lineage a million years ago, well before the separation between modern humans and Neanderthals.

Although it was very small, the fragment of Denisovan bone was well preserved, and as the work on the Neanderthal genome was drawing to a close, Pääbo decided to study the Denisovan DNA. This turned out to be from a young girl aged four or five. Although the Denisovan DNA was different both from modern humans and from Neanderthals, there were also similarities.

Using the Denisovan and Neanderthal genome data, David [Reich] and Nick [Patterson] estimated that about 2.5 per cent of the genomes of people outside Africa came from Neanderthals, and that later gene flow had brought about 4.8 per cent of Denisovan DNA into the Papuans. Since Papuans also carried the Neanderthal component in their genome,this meant that approximately 7 per cent of the genomes of Papuans came from earlier forms of humans. This was an amazing finding. … Thus, low levels of mixing with earlier humans seemed to have been the rule rather than the exception when modern humans spread across the world. This meant that neither Neanderthals nor Denisovans were totally extinct. A little bit of them lives on in people today.
The Denisovans must have been widespread in the past, although they don't seem to have mixed with modern humans in mainland Asia. This may mean that, as many palaeontologists believe, the earliest human migrations took place along the coastline, and movement inland occurred only after the Denisovans had disappeared.

In a postscript Pääbo outlines the research that his laboratory is currently doing. He says that new techniques have allowed the sequencing of Denisovan and Neanderthal genomes to higher accuracy than for most genomes derived from people living today.

Pääbo writes well and manages to convey a good deal of technical material in a readable form. He gives full credit to his team, and indeed it is clear that his success has been partly due to the skill with which he assembled and managed a group of often unusual individuals. Team photographs are included but the reproductions are poor and few details can be made out.


%T Neanderthal Man
$S In Search of Lost Genomes
%A Svante Pääbo
%I Basic Books
%C New York
%D 2014
%G ISBN 9780465020836
%P 275pp
%K evolution
%O halftone illustrations

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