Complete Neanderthal Mitochondrial Genome Sequenced from Bone

Recent research has revealed the complete mitochondrial genome of a 38,000-year-old Neanderthal (Homo neanderthalensis). The findings provide insights into the Neanderthals' past and help answer remaining questions about their relationship to modern humans.

"For the first time, we've built a sequence from ancient DNA that is essentially without error,” said Dr. Richard Green from the Max Planck Institute for Evolutionary Anthropology (Leipzig Germany), who published his findings in the August 8, 2008, issue of the journal Cell .

The investigators sequenced Neanderthal mitochondria DNA--including 13 protein-coding genes--nearly 35 times over. That remarkable coverage allowed them to sift out those differences between the Neanderthal and human genomes resulting from damage to the degraded DNA extracted from ancient bone versus real evolutionary changes.

Although it is well established that Neanderthals are the hominid form most closely related to modern-day humans, their precise relationship remains uncertain, according to the researchers. The notion that Neanderthals and humans may have "mixed” is still a matter of some controversy.

Analysis of the new sequence confirms that the mitochondria of Neanderthal's falls outside the variation found in humans today, providing no proof of admixture between the two lineages although it remains a possibility. The data also demonstrate that the last common ancestor of Neanderthals and humans lived approximately 660,000 years ago, for about 140,000 years.

Of the 13 proteins encoded in the mitochondrial DNA, the researchers discovered that one, known as subunit 2 of cytochrome c oxidase of the mitochondrial electron transport chain (COX2), had experienced an unexpected number of amino acid substitutions in humans since the separation from Neanderthals. While the finding is fascinating, according to Dr. Green, it is not yet clear what it means.

"We also wanted to know about the history of the Neanderthal's themselves,” said Dr. Jeffrey Good, also of the Max-Planck Institute. For instance, the new sequence information revealed that Neanderthal's have fewer evolutionary alterations overall, but a greater number that alter the amino acid building blocks of proteins. One simple interpretation of that finding is that the Neanderthal's had a smaller population size than humans do, which makes natural selection less successful in removing mutations.

That theory is consistent with arguments made by other scientists based upon the geologic record, said co-author Johannes Krause. "Most argue there were a few thousand Neanderthals that wandered over Europe 40,000 years ago.” That smaller population might have been the result of the smaller size of Europe compared to Africa. The Neanderthals also would have had to deal with repeated glaciations, he noted.

"It's still an open question for the future whether this small group of Neanderthals was a general feature, or was this caused by some bottleneck in their population size that happened late in the game,” Dr. Green said. Eventually, they hope to get DNA sequence information for Neanderthals that predated the Ice Age, to look for a signature that their populations had been larger in the past.

To be precise, the Neanderthal mitochondrial genome presented in the new study is a useful precursor for the sequencing of the complete Neanderthal nuclear genome, according to the researchers, an accomplishment that their team already has well underway.

Related Links:
Max Planck Institute for Evolutionary Anthropology