Industry News: 454 Life Sciences and Max Planck Institute Complete Draft 1X Sequence of Neanderthal Genome

12 Feb 2009

Completion of more than 3 billion bases of sequenced Neanderthal DNA brings closure to the sequencing stage of an ambitious project initiated two and a half years ago. Announcement of bonobo genome draft sequence opens new doors to understanding the evolutionary history of humans and apes.

In a press conference held on February 12 in Leipzig, Germany, and simultaneously at the AAAS Annual Meeting in Chicago, researchers from the Max Planck Institute for Evolutionary Anthropology and 454 Life Sciences announced the completion of the 1X draft sequence of the Neanderthal genome. The announcement draws closure to an ambitious sequencing project initiated by the team in July 2006 and highlights the tremendous technological advancements necessary to achieve this breakthrough in molecular anthropology. The team also announced the completion of the 18-fold draft sequence of the Bonobo genome, an endangered ape closely related to the Common Chimpanzee and distantly to humans. Detailed analysis of both the Neanderthal and Bonobo genomes will significantly advance our understanding of the human evolutionary history.

The Neanderthal project, spearheaded by Dr. Svante Pääbo, Director of the Institute’s Department of Evolutionary Anthropology and Michael Egholm, Chief Technology Officer at 454 Life Sciences, developed from the results of a study published in Nature in 2006, detailing the ability of 454 Sequencing to determine large amounts of nuclear DNA sequences from late Pleistocene animals such as cave bears, mammoths, as well as the Neanderthal. The goal of the project is to identify areas in the genome where humans have undergone rapid evolution since the split from Neanderthals: the genetic changes that define us as human. This analysis is achieved by comparing the Neanderthal reference to the human and chimpanzee reference genome sequences as well as to the genomic variation among humans today.

Together the groups have overcome a number of steep technical obstacles in order to arrive at this first view of the extinct form of human, including difficulties with highly-degraded and contaminated DNA and the limited availability of precious fossil material. A number of key milestones have been achieved over the course of the project, including the complete mitochondrial genome sequence, published in Cell in 2008. Using the chimpanzee and human mitochondrial DNA sequences as reference points, the number of nucleotide differences found in the Neanderthal mitochondrial DNA establishes the divergence date between human and Neanderthal mtDNAs at 660,000 +/- 140,000 years.

The final draft sequence includes more than three billion bases of Neanderthal DNA and covers approximately two-thirds of the genome. During the last phase of the project, micro-reads generated by the Solexa technology were used to achieve the one-fold coverage. In order to aid in the analysis of the Neanderthal genome, Dr. Pääbo has organized a consortium of researchers from around the world that plans to publish their results later this year.

Commenting on the collaboration between the Max Planck Institute and 454 Life Sciences Dr. Pääbo said, “It has been a great experience working with the 454 team. It has taught me that it is truly possible work with industry with the focus solely on the science.” He continued, “The 454 Sequencing technology has revolutionized this entire field and we are applying its unique features for the sequencing of the Bonobo genome.” Along with the Common Chimpanzee, the Bonobo is the closest relative to humans and, like the human genome, is highly complex. In fact, the relationship between the Bonobo and the Chimpanzee is in many ways analogous to the relationship between Neanderthals and humans.

“We are proud to have spearheaded, along with the Max Planck Institute, such a groundbreaking achievement in our understanding of human evolutionary history,” said Michael Egholm. “454 Sequencing continues to revolutionize the field of molecular anthropology, enabling not only the Neanderthal genome but also the complex genomes of living human relatives, like the Bonobo.”