The Iceman’s mysterious genetic past

It’s been 17 years since a prehistoric man’s frozen body was found poking out of a glacier in the Italian Alps, and the mummified corpse continues to warm scientists’ hearts. The Tyrolean Iceman, or Ötzi, now has yielded the oldest complete human mitochondrial DNA sequence generated to date, say molecular biologist Franco Rollo of the University of Camerino, Italy, and his colleagues.

Mitochondria are molecular structures that provide power to cells. Because the structures contain DNA that is passed from mothers to their children, a mitochondrial DNA sequences provides a view of a person’s female ancestry.

“This study further confirms that, with new sequencing approaches, mitochondrial DNA from ancient samples can be completely sequenced,” remarks geneticist Antonio Torroni of the University of Pavia, Italy.

Ötzi, who lived between 5,350 and 5,100 years ago, belonged to a branch of a mitochondrial DNA line that has yet to be identified in modern Europeans, Rollo’s team reports in a paper published online October 30 in Current Biology. Ötzi’s ancient genetic comrades may have gotten swamped by other mitochondrial DNA lines as people congregated in increasingly larger settlements, the scientists suggest. Random changes in the mitochondrial DNA of Ötzi’s peers may have contributed to the absence of a match as well.

Further genetic studies of modern Europeans might identify some who belong to what Rollo’s group has dubbed “Ötzi’s branch.”

“Through the analysis of a complete mitochondrial genome in a particularly well-preserved body, we have obtained evidence of a significant genetic difference between present-day Europeans and a prehistoric human, despite the fact that the Iceman is only about 5,000 years old,” Rollo says.

Researchers estimate that the Iceman was approximately 46 years old when he was severely wounded by an arrow and then killed by a mace blow to the face. Rollo’s team isolated genetic material from Ötzi’s intestines in order to minimize the possibility of DNA contamination from human handling of the body.

Ancient DNA, whether from mitochondria or cell nuclei, is highly prone to contamination from human handling and chemicals used in laboratory tests, says evolutionary biologist Eske Willerslev of the University of Copenhagen. Due to its nonporous structure, hair proves especially resistant to such contamination, in his view.

“Because the Rollo team used intestinal material from the mummy, it is difficult to exclude the possibility that their unique mitochondrial DNA lineage is a result of contaminant DNA mixing in with Ötzi’s own genetic sequences,” Willerslev remarks.

In 2006, Rollo and his coworkers reported that fragments of mitochondrial DNA recovered from the Iceman’s intestines showed that he belonged to a lineage known as K1. About 8 percent of modern Europeans belong to the K haplogroup, meaning that they share a common maternal ancestor. That haplogroup is divided into K1 and K2 lineages. Studies on modern Europeans before 2006 identified three branches of the K1 lineage.

In the new study, the researchers used advanced genome-sequencing technologies to retrieve a complete version of Ötzi’s mitochondrial DNA. A comparison to 115 complete haplogroup K genomes from modern Europeans showed that the prehistoric man came from a newly identified, fourth branch of K1.

It’s possible but unlikely that Ötzi belonged to a fourth branch of K1 that is now extinct or rare, Torroni says. He considers it more probable that a random mutation in the Iceman’s mitochondrial DNA erased the only genetic marker currently used to identify members of the most common K1 branch.

Complete mitochondrial genomes of ancient people remain rare. One such sequence comes from the frozen hair of a person who lived in Greenland between 4,500 and 3,400 years ago. In the June 27 Science, a team led by Willerslev reported that this individual’s mitochondrial DNA differs substantially from that of later Eskimos and that of modern Native Americans.

The Greenland individual does display genetic links to modern Aleuts and Siberians, suggesting that the earliest New World migrants came from the Bering Sea area and were later replaced by other populations, the researchers conclude.

Another team recently isolated a complete mitochondrial DNA sequence from a 38,000-year-old Neandertal bone. Many researchers classify Neandertals as a species separate from modern humans.