New Insights into the Tyrolean Iceman's Origin and Phenotype As Inferred by Whole-genome Sequencing

Overview

Journal Nat Commun

Specialty Biology

Date 2012 Mar 20

PMID 22426219

Citations 174

Authors

Andreas Keller

Angela Graefen

Markus Ball

Mark Matzas

Valesca Boisguerin

Frank Maixner

Petra Leidinger

Christina Backes

Rabab Khairat

Michael Forster

Bjorn Stade

Andre Franke

Jens Mayer

Jessica Spangler

Stephen McLaughlin

Minita Shah

Clarence Lee

Timothy T Harkins

Alexander Sartori

Andres Moreno-Estrada

Brenna Henn

Martin Sikora

Ornella Semino

Jacques Chiaroni

Siiri Rootsi

Natalie M Myres

Vicente M Cabrera

Peter A Underhill

Carlos D Bustamante

Eduard Egarter Vigl

Marco Samadelli

Giovanna Cipollini

Jan Haas

Hugo Katus

Brian D OConnor

Marc R J Carlson

Benjamin Meder

Nikolaus Blin

Eckart Meese

Carsten M Pusch

Albert Zink

Affiliations

Soon will be listed here.

Abstract

The Tyrolean Iceman, a 5,300-year-old Copper age individual, was discovered in 1991 on the Tisenjoch Pass in the Italian part of the Ötztal Alps. Here we report the complete genome sequence of the Iceman and show 100% concordance between the previously reported mitochondrial genome sequence and the consensus sequence generated from our genomic data. We present indications for recent common ancestry between the Iceman and present-day inhabitants of the Tyrrhenian Sea, that the Iceman probably had brown eyes, belonged to blood group O and was lactose intolerant. His genetic predisposition shows an increased risk for coronary heart disease and may have contributed to the development of previously reported vascular calcifications. Sequences corresponding to ~60% of the genome of Borrelia burgdorferi are indicative of the earliest human case of infection with the pathogen for Lyme borreliosis.

Citing Articles

Sequencing and characterizing human mitochondrial genomes in the biobank-based genomic research paradigm.

Luo L, Wang M, Liu Y, Li J, Bu F, Yuan H Sci China Life Sci. 2025; .

PMID: 39843848 DOI: 10.1007/s11427-024-2736-7.

The Allen Ancient DNA Resource (AADR) a curated compendium of ancient human genomes.

Mallick S, Micco A, Mah M, Ringbauer H, Lazaridis I, Olalde I Sci Data. 2024; 11(1):182.

PMID: 38341426 PMC: 10858950. DOI: 10.1038/s41597-024-03031-7.

Stable population structure in Europe since the Iron Age, despite high mobility.

Antonio M, Weiss C, Gao Z, Sawyer S, Oberreiter V, Moots H Elife. 2024; 13.

PMID: 38288729 PMC: 10827293. DOI: 10.7554/eLife.79714.

Genetic Predisposition of Atherosclerotic Cardiovascular Disease in Ancient Human Remains.

Wurst C, Maixner F, Paladin A, Mussauer A, Valverde G, Narula J Ann Glob Health. 2024; 90(1):6.

PMID: 38273870 PMC: 10809863. DOI: 10.5334/aogh.4366.

Ancestry and kinship in a Late Antiquity-Early Middle Ages cemetery in the Eastern Italian Alps.

Coia V, Paladin A, Zingale S, Wurst C, Croze M, Maixner F iScience. 2023; 26(11):108215.

PMID: 37953960 PMC: 10637928. DOI: 10.1016/j.isci.2023.108215.

References

Rollo F, Ermini L, Luciani S, Marota I, Olivieri C, Luiselli D . Fine characterization of the Iceman's mtDNA haplogroup. Am J Phys Anthropol. 2006; 130(4):557-64. DOI: 10.1002/ajpa.20384. View

Rasmussen M, Li Y, Lindgreen S, Pedersen J, Albrechtsen A, Moltke I . Ancient human genome sequence of an extinct Palaeo-Eskimo. Nature. 2010; 463(7282):757-62. PMC: 3951495. DOI: 10.1038/nature08835. View

Sturm R, Duffy D, Zhao Z, Leite F, Stark M, Hayward N . A single SNP in an evolutionary conserved region within intron 86 of the HERC2 gene determines human blue-brown eye color. Am J Hum Genet. 2008; 82(2):424-31. PMC: 2427173. DOI: 10.1016/j.ajhg.2007.11.005. View

Handt O, Krings M, Ward R, Paabo S . The retrieval of ancient human DNA sequences. Am J Hum Genet. 1996; 59(2):368-76. PMC: 1914746. View

Novembre J, Stephens M . Interpreting principal component analyses of spatial population genetic variation. Nat Genet. 2008; 40(5):646-9. PMC: 3989108. DOI: 10.1038/ng.139. View

Chen S, Ballantyne C, Gotto Jr A, Marian A . The 9p21 susceptibility locus for coronary artery disease and the severity of coronary atherosclerosis. BMC Cardiovasc Disord. 2009; 9:3. PMC: 2637231. DOI: 10.1186/1471-2261-9-3. View

Ginolhac A, Rasmussen M, Gilbert M, Willerslev E, Orlando L . mapDamage: testing for damage patterns in ancient DNA sequences. Bioinformatics. 2011; 27(15):2153-5. DOI: 10.1093/bioinformatics/btr347. View

Murphy Jr W, Nedden Dz D, Gostner P, Knapp R, Recheis W, Seidler H . The iceman: discovery and imaging. Radiology. 2003; 226(3):614-29. DOI: 10.1148/radiol.2263020338. View

Haak W, Balanovsky O, Sanchez J, Koshel S, Zaporozhchenko V, Adler C . Ancient DNA from European early neolithic farmers reveals their near eastern affinities. PLoS Biol. 2010; 8(11):e1000536. PMC: 2976717. DOI: 10.1371/journal.pbio.1000536. View

10.

Yamamoto F, Clausen H, White T, Marken J, Hakomori S . Molecular genetic basis of the histo-blood group ABO system. Nature. 1990; 345(6272):229-33. DOI: 10.1038/345229a0. View

11.

Sims L, Garvey D, Ballantyne J . Improved resolution haplogroup G phylogeny in the Y chromosome, revealed by a set of newly characterized SNPs. PLoS One. 2009; 4(6):e5792. PMC: 2686153. DOI: 10.1371/journal.pone.0005792. View

12.

He Y, Wu J, Dressman D, Iacobuzio-Donahue C, Markowitz S, Velculescu V . Heteroplasmic mitochondrial DNA mutations in normal and tumour cells. Nature. 2010; 464(7288):610-4. PMC: 3176451. DOI: 10.1038/nature08802. View

13.

Ermini L, Olivieri C, Rizzi E, Corti G, Bonnal R, Soares P . Complete mitochondrial genome sequence of the Tyrolean Iceman. Curr Biol. 2008; 18(21):1687-93. DOI: 10.1016/j.cub.2008.09.028. View

14.

Branicki W, Brudnik U, Wojas-Pelc A . Interactions between HERC2, OCA2 and MC1R may influence human pigmentation phenotype. Ann Hum Genet. 2009; 73(2):160-70. DOI: 10.1111/j.1469-1809.2009.00504.x. View

15.

Yasuda H, Kamide K, Takiuchi S, Matayoshi T, Hanada H, Kada A . Association of single nucleotide polymorphisms in endothelin family genes with the progression of atherosclerosis in patients with essential hypertension. J Hum Hypertens. 2007; 21(11):883-92. DOI: 10.1038/sj.jhh.1002234. View

16.

Hawass Z, Gad Y, Ismail S, Khairat R, Fathalla D, Hasan N . Ancestry and pathology in King Tutankhamun's family. JAMA. 2010; 303(7):638-47. DOI: 10.1001/jama.2010.121. View

17.

McPherson R, Pertsemlidis A, Kavaslar N, Stewart A, Roberts R, Cox D . A common allele on chromosome 9 associated with coronary heart disease. Science. 2007; 316(5830):1488-91. PMC: 2711874. DOI: 10.1126/science.1142447. View

18.

Handt O, Richards M, Trommsdorff M, Kilger C, Simanainen J, Georgiev O . Molecular genetic analyses of the Tyrolean Ice Man. Science. 1994; 264(5166):1775-8. DOI: 10.1126/science.8209259. View

19.

Luke M, Lalouschek W, Rowland C, Catanese J, Bolonick J, Bui N . Polymorphisms associated with both noncardioembolic stroke and coronary heart disease: vienna stroke registry. Cerebrovasc Dis. 2009; 28(5):499-504. PMC: 2818395. DOI: 10.1159/000236914. View

20.

Henn B, Botigue L, Gravel S, Wang W, Brisbin A, Byrnes J . Genomic ancestry of North Africans supports back-to-Africa migrations. PLoS Genet. 2012; 8(1):e1002397. PMC: 3257290. DOI: 10.1371/journal.pgen.1002397. View