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Neanderthal Mitochondrial Genome Sequence Published

By R&D Editors | August 13, 2008

Researchers led by the Max-Planck Institute for Evolutionary Anthropology in Leipzig, Germany have published the complete Neanderthal mitochondrial genome sequence. The mitochondrial genome was generated using the 454 Sequencing technology to 35-fold redundancy, facilitating a detailed comparison against known human mitochondrial genomes and an analysis of recent human evolution.

The complete mitochondrial genome sequence was reconstructed from DNA obtained from a 38,000 year old Neanderthal bone fragment excavated in 1980 from the Vindija Cave, Croatia. Analysis of the assembled sequence unequivocally establishes that the Neanderthal mitochondrial DNA falls outside the variation of extant human mtDNAs, showing that Neanderthals did not contribute mtDNA to present-day humans. Furthermore, 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.

“We are very excited to bring full scale genomic analysis to the study of our closest extinct relative. The mitochondrial result is only the tip of the iceberg as we push towards the completion of a whole Neanderthal genome sequence,” said Dr. Svante Pääbo, Ph.D. Senior Author on the paper and Director of the Department of Genetics at the Max Planck Institute for Evolutionary Anthropology.
The mitochondrial sequence data presented in the current study was generated as part of the Neanderthal Genome Project, an effort to sequence the entire nuclear genome of the Neanderthal. The mitochondrial sequencing is an important milestone towards the goal of whole Neanderthal sequencing as it demonstrates that ancient, degraded DNA can be sequenced accurately using the technology of the 454 Sequencing System and assembled into a consensus sequence. Given the mitochondrial genome’s smaller size relative to the nuclear genome and their abundance in cells, where typically several hundred mtDNAs per nuclear genome exist, its sequencing was the logical first step in the full scale analysis of the Neanderthal genome.

The key deliverable for the Neanderthal Genome Project is to generate a Neanderthal genome sequence to be used as a reference point in the study of recent human evolution. The overarching purpose 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. A significant result from the mtDNA genome sequence validates this approach: of the 13 proteins encoded in the mitochondrial DNA, one gene, subunit 2 of cytochrome c oxidase, is identified as having experienced a surprisingly large number of amino acid substitutions in modern humans since the split from Neanderthals. The project that was announced two years ago is expected to be completed later this year when a one-fold coverage of the Neanderthal genome is achieved.

“This exciting result from the Neanderthal Genome Project gives us a tantalizing look at the types of human evolutionary questions the community will be able to answer with a complete Neanderthal genome sequence” said Dr. Michael Egholm, Vice President of Research and Development at 454 Life Sciences. “Molecular anthropology is one of many fields revolutionized by the 454 Sequencing System´s long highly-accurate reads, simple workflow, and ultra-high throughput.

Release date: August 8, 2008
Source: Roche Applied Science

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