New Microarray Technology Enables Sequencing of Neanderthal DNA

By utilizing an advanced DNA capture technique, genomic researchers have succeeding in mapping a portion of the Neanderthal genome and comparing it to that of modern humans.

Investigators at the Max Planck Institute (Munich, Germany) , Cold Spring Harbor Laboratory (Cold Spring Harbor, NY, USA), and Agilent Technologies, Inc. (Santa Clara, CA, USA) used Agilent's microarray system to sequence nearly 14,000 protein-coding positions inferred to have changed on the human lineage since the last common ancestor shared with chimpanzees.

Generally, it has been extremely difficult to work with ancient DNA due in part to chemical aging of the DNA molecules but even more so due to severe bacterial contamination of the samples. Now, in a study published in the May 7, 2010, issue of the journal Science, investigators from the three institutions described the use of array-hybridization capture technology, a process that enriched Neanderthal DNA sequences while depleting contaminant DNA. Thus, they were able to enrich Neanderthal protein-coding regions where differences occurred on the human evolutionary lineage up to 190,000-fold. By generating the sequence of one Neanderthal and 50 present-day humans, the investigators identified 88 amino acid substitutions that have become fixed in humans since our divergence from the Neanderthals.

"Attaining good coverage of the Neanderthal genome had been a problem due to DNA contamination from microbes over the years,” said senior investigator Dr. Svante Paabo, professor of evolutionary genetics at the Max Planck Institute. "Simply sequencing, without first enriching for the genome, often did not work, especially where the contamination levels were high. Array-hybridization capture technology was originally reported by the Cold Spring Harbor Laboratory group and is the subject of a longstanding collaboration with Agilent. The team recognized this as a promising method for recovering large regions of targeted sequence from Neanderthal samples. The method can also be used more widely with many other kinds of human remains.”

In a second article in the same issue of Science, the investigators presented their first detailed analysis of the draft sequence of the Neanderthal genome, which now includes more than three billion nucleotides collected from the bones of three female Neanderthals who lived in Croatia more than 38,000 years ago. By comparing this composite Neanderthal genome with the complete genomes of five living humans from different parts of the world, the investigators found that both Europeans and Asians share 1-4% of their nuclear DNA with Neanderthals, but that Africans do not. This suggests that early modern humans interbred with Neanderthals after moderns left Africa, but before they spread into Asia and Europe.

Related Links:
Max Planck Institute
Cold Spring Harbor Laboratory
Agilent Technologies