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Hair yields ancient DNA

Researchers extract complete mitochondrial genomes from mammoth coat-hair shafts


[Published 27th September 2007 03:31 PM GMT]


Ancient samples of animal hair shafts can yield complete, high-quality mitochondrial genomes, even when the hair has been kept at room temperature for hundreds of years, reports this week's Science. According to the researchers, the finding suggests that scientists may be able to perform genomic analyses on animal specimens stored in natural history museums.

"This, of course, is amazing, because the mantra is that you want specimens straight out of the permafrost that you keep frozen," said Ross MacPhee of the American Museum of Natural History in New York City, who was not involved in the work.

Researchers have used various genetic methods to extract both mitochondrial and nuclear DNA from ancient specimens, usually bones. Although they've managed to recover DNA from extinct species such as wooly mammoths and giant flightless birds, "false positive results have plagued ancient DNA for a long time," Michael Holfreiter of the Max Planck Institute for Evolutionary Anthropology in Germany, also not a co-author, wrote in an Email. "Ancient DNA got a bad rap in the '90s because of contamination issues," MacPhee agreed.

Whole-genome shotgun sequencing now allows scientists to sequence ancient DNA more reliably, especially when using sequencing-by-synthesis. In this technique, each DNA molecule in a sample is amplified individually and therefore not contaminated by human or bacterial DNA. Researchers have already used this method to sequence nuclear DNA from Neanderthal and mammoth bones. However, many bones do not yield enough DNA to make the technique economical, according to the authors.

To see if hair shafts offer an attractive alternative source of mitochondrial DNA, Thomas Gilbert of the University of Copenhagen and his colleagues used sequencing-by-synthesis to sequence DNA extracted from the mitochondria of wooly mammoth coat hair cells. They successfully assembled full mitochondrial genome sequences from 10 samples of mammoth hair from northern Siberia.

The mitochondrial DNA yield was between five and 26 times higher than that previously extracted from mammoth bone, probably because hair shafts contain many more mitochondria than bone cells do, said senior author Stephan Schuster of Pennsylvania State University in University Park.

The researchers also found that DNA from hair shafts was significantly less damaged than DNA from mammoth bone -- even though the bone samples were frozen prior to analysis while the hair had been stored at room temperature for years. One hair sample, from the first mammoth to be studied scientifically, was stored at room temperature for more than 200 years, yet it retained viable mitochondrial DNA.

Schuster said it is unclear why mitochondrial DNA from hair shafts is longer-lasting than DNA from bone, although the researchers suspect that the protective nature of the shaft itself may have something to do with it. "The melanin material in the hair is like a biological plastic," he said, while "the bone is more like a sponge." Bacteria that secrete DNA-damaging enzymes can access bone DNA, while hair cells block access to their DNA.

"The data presented show convincingly that it is a good technique -- provided hair is available," Holfreiter said. However, this "is not the case for that many extinct species," he added.

For now, bones may remain better sources for nuclear DNA, according to MacPhee. In hair cells, "very often you don't have nucleated cells, so you're just dealing with mitochondria," he said. "Of course, with the high sensitivity of the procedures and protocols that are available now, if it's there, you'll get it. But it might take a lot more effort and therefore a lot more cost."

According to Schuster, the researchers "most excited about our findings are museum curators." Museums often have a "type specimen" for each species -- usually the first individual discovered and thoroughly described. "We hope in the future that we can add genetic information and also maybe complete genomes to these type specimens," Schuster said. "We basically want to bring the genomic component to the museums."

Melissa Lee Phillips
mail@the-scientist.com

Links within this article

C.Q. Choi, "How mtDNA mutations cause aging," The Scientist, July 15, 2005.
http://www.the-scientist.com/article/display/22731/

M.T.P. Gilbert et al., "Whole-genome shotgun sequencing of mitochondria from ancient hair shafts," Science, September 28, 2007. http://www.sciencemag.org

Ross MacPhee
http://www.amnh.org

E.I. Rogaev et al., "Complete mitochondrial genome and phylogeny of Pleistocene mammoth Mammuthus primigenius," PLoS Biology, March 2006.
http://www.the-scientist.com/pubmed/16448217

A. Cooper et al., "Complete mitochondrial genome sequences of two extinct moas clarify ratite evolution," Nature, February 8, 2001.
http://www.the-scientist.com/pubmed/11217857

Michael Holfreiter
http://www.eva.mpg.de/genetics/staff/hofreiter/index.html

T.M. Powledge, "Shotgun sequencing comes of age," The Scientist, December 31, 2002.
http://www.the-scientist.com/news/20021231/06/

M. Margulies et al., "Genome sequencing in microfabricated high-density picolitre reactors," Nature, September 15, 2005.
http://www.the-scientist.com/pubmed/16056220

J.P. Noonan et al., "Sequencing and analysis of Neanderthal genomic DNA," Science, November 17, 2006.
http://www.the-scientist.com/pubmed/17110569

H.N. Poinar et al., "Metagenomics to paleogenomics: large-scale sequencing of mammoth DNA," Science, January 20, 2006.
http://www.the-scientist.com/pubmed/16368896

D. Secko, "Combing for ancient DNA," The Scientist, July 19, 2004.
http://www.the-scientist.com/article/display/14836/

Thomas Gilbert
http://www.bi.ku.dk/staff/person.asp?ID=520

M.T.P. Gilbert et al., "Recharacterization of ancient DNA miscoding lesions: insights in the era of sequencing-by-synthesis," Nucleic Acids Research, 2007.
http://www.the-scientist.com/pubmed/16920744

E.J. Van Scott et al., "Determinants of rate and kinetics of cell division in scalp hair," Journal of Investigative Dermatology, November 1963.
http://www.the-scientist.com/pubmed/14075450

Stephan Schuster
http://www.bmb.psu.edu/faculty/schuster/schuster_lab/home.html

I.P. Tolmachoff, "The carcasses of the mammoth and rhinoceros found in the frozen ground of Siberia," Transactions of the American Philosophical Society, 1929.
http://www.jstor.org/


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This fascinating paper inform about the importance of Biophysical Semeiotics.
by Sergio Stagnaro MD

[Comment posted 2007-09-28 05:03:23]
Sirs,
I is a great honour, as usually, to see my comments posted in a famous website like PLOS (and The Scientist, to, of course). However, the following comment is worthwhile of accurate consideration. Please, read it:


26 July 2007

Plos-Biology
Editors,
I consider this article really fascinating and interesting as regards particularly the human most common and serious disorders. In fact, determining the complete mitochondrial genome of the mastodon (Mammut americanum), a recently extinct relative of the living elephants that diverged about 26 million years ago, the authors obtained the sequence from a tooth dated to 50,000?130,000 years ago, increasing the specimen age for which such palaeogenomic analyses have been done by almost a complete glacial cycle. Using this sequence, together with mitochondrial genome sequences from two African elephants, two Asian elephants, and two woolly mammoths these scientists have clearly shown that mammoths are more closely related to Asian than to African elephants, underlining, although unintentionally, the fact that mitochondrial equipment lay a central role in individual constitutions, as I demonstrated in former papers in my 51-year-long clinical research, posted also in PLOS (1-7). In a few words, all biophysical-semeiotic constitutions, in both man and animal, are dependent of an inherited mitochondrial cytopathy, I termed Congenital Acidosic Enzyme-Metabolic Histangiopathy (CAEM), Single Patient Based Medicine is based on (3, 6, 7).
References

1) Stagnaro-Neri M., Stagnaro S. Introduzione alla Semeiotica Biofisica. Il Terreno Oncologico. Ed. Travel Factory, Roma, 2004. LINK
2) Stagnaro S., Stagnaro-Neri M., Le Costituzioni Semeiotico-Biofisiche.Strumento clinico fondamentale per la prevenzione primaria e la definizione della Single Patient Based Medicine. Ed. Travel Factory, Roma, 2004.
3) Stagnaro S., Stagnaro-Neri M. Single Patient Based Medicine.La Medicina Basata sul Singolo Paziente: Nuove Indicazioni della Melatonina. Ed. Travel Factory, Roma, 2005.
4) Stagnaro S., Istangiopatia Congenita Acidosica Enzimo-Metabolica. Gazz Med. It. ? Asch. Sci, Med. 144, 423, 1985
5) Stagnaro S., West PJ., Hu FB., Manson JE., Willett WC. Diet and Risk of Type 2 Diabetes. N Engl J Med. 2002 Jan 24;346(4):297-298. [Medline]
6) Stagnaro Sergio. Single Patient Based Medicine: its paramount role in Future Medicine. Public Library of Science. 2005. LINK
7) Stagnaro S. Pivotal role of Biophysical Semeiotic Constitutions in Primary Prevention. Cardiovascular Diabetology, 2:1, LINK


In fact, mitochondria alterations, as the mitochondrial cytopathy, I termed 30 years ago Congenital Acidosic Enzyme-Metabolic Histangiopathy, play a central role in ALL biophysical-semeiotic constitutions, relative Inherited Real Risks, and most common and severe human disorders, including diabetes and cancer.
Finally, these CLINICAL tools allow fortunately physicians around the world to performe SINCE BIRTH an efficacious, not expensive, primary prevention in individuals enrolled rationally (www.semeioticabiofisica.it).



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