Letter | Published:

Substitutions in woolly mammoth hemoglobin confer biochemical properties adaptive for cold tolerance

Nature Genetics volume 42, pages 536540 (2010) | Download Citation

Abstract

We have genetically retrieved, resurrected and performed detailed structure-function analyses on authentic woolly mammoth hemoglobin to reveal for the first time both the evolutionary origins and the structural underpinnings of a key adaptive physiochemical trait in an extinct species. Hemoglobin binds and carries O2; however, its ability to offload O2 to respiring cells is hampered at low temperatures, as heme deoxygenation is inherently endothermic (that is, hemoglobin-O2 affinity increases as temperature decreases). We identify amino acid substitutions with large phenotypic effect on the chimeric β/δ-globin subunit of mammoth hemoglobin that provide a unique solution to this problem and thereby minimize energetically costly heat loss. This biochemical specialization may have been involved in the exploitation of high-latitude environments by this African-derived elephantid lineage during the Pleistocene period. This powerful new approach to directly analyze the genetic and structural basis of physiological adaptations in an extinct species adds an important new dimension to the study of natural selection.

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Acknowledgements

We thank T. Kuznetsova for the mammoth samples, W. Korver for providing Asian and African elephant blood and A. Bang, T.C. Tam, N. Ho, J. Hare, J. da Silva and M. Pagel for technical assistance. Financial support was provided by the National Sciences and Engineering Research Council (NSERC) of Canada (K.L.C. and J.S.), Winnipeg Foundation (K.L.C.), University of Manitoba Research Grant Program (K.L.C.), Japan Society for the Promotion of Science (J.R.H.T.), Max Planck Society (M.H. and N.R.), US National Institutes of Health grant R01GM-084614; C.H.), Danish Natural Science Research Council and the Carlsberg Foundation (R.E.W.) and the Australian Research Council (A.C. and L.N.W.). J.E.E.R., J.W.H. and A.V.S. were supported by NSERC Undergraduate Research Awards, and A.M.S. was supported by a University of Manitoba Graduate Fellowship.

Author information

Author notes

    • Nadin Rohland

    Present address: Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.

    • Michael Hofreiter

    Present address: Department of Biology, University of York, York, UK.

    • Roy E Weber
    •  & Alan Cooper

    These authors contributed equally to this work.

Affiliations

  1. Department of Biological Sciences, University of Manitoba, Winnipeg, Canada.

    • Kevin L Campbell
    • , Jason E E Roberts
    • , Angela M Sloan
    • , Anthony V Signore
    •  & Jesse W Howatt
  2. Australian Centre for Ancient DNA, School of Earth and Environmental Sciences, University of Adelaide, Adelaide, Australia.

    • Laura N Watson
    • , Jeremy J Austin
    •  & Alan Cooper
  3. Department of Chemistry, University of Manitoba, Winnipeg, Canada.

    • Jörg Stetefeld
  4. Protein Design Laboratory, Yokohama City University, Yokohama, Japan.

    • Jeremy R H Tame
  5. Junior Research Group Molecular Ecology, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.

    • Nadin Rohland
    •  & Michael Hofreiter
  6. Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA.

    • Tong-Jian Shen
    •  & Chien Ho
  7. Zoophysiology, Institute of Biological Sciences, University of Aarhus, Aarhus, Denmark.

    • Roy E Weber

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Contributions

K.L.C. conceived the research. K.L.C., J.S., M.H., J.J.A., T.-J.S., C.H., R.E.W. and A.C. designed the experiments. K.L.C., J.E.E.R., L.N.W., A.M.S., A.V.S., J.W.H., N.R., T.-J.S., R.E.W. and J.J.A. conducted the experiments. K.L.C., J.S., A.V.S., J.R.H.T., R.E.W. and A.C. analyzed the data. K.L.C. and A.C. drafted the manuscript, and K.L.C., M.H., J.R.H.T., C.H., R.E.W. and A.C. contributed to the final manuscript writing and its revisions.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Kevin L Campbell or Alan Cooper.

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DOI

https://doi.org/10.1038/ng.574

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