Evolution of an extreme hemoglobin phenotype contributed to the sub-Arctic specialization of extinct Steller's sea cows

  1. Anthony V Signore
  2. Phillip R Morrison
  3. Colin J Brauner
  4. Angela Fago
  5. Roy E Weber
  6. Kevin L Campbell  Is a corresponding author
  1. University of Manitoba, Canada
  2. University of British Columbia, Canada
  3. Aarhus University, Denmark

Abstract

The extinct Steller's sea cow (Hydrodamalis gigas; †1768) was a whale-sized marine mammal that manifested profound morphological specializations to exploit the harsh coastal climate of the North Pacific. Yet despite first-hand accounts of their biology, little is known regarding the physiological adjustments underlying their evolution to this environment. Here, the adult-expressed hemoglobin (Hb; a2β/δ2) of this sirenian is shown to harbor a fixed amino acid replacement at an otherwise invariant position (β/δ82Lys→Asn) that alters multiple aspects of Hb function. First, our functional characterization of recombinant sirenian Hb proteins demonstrate that the Hb-O2 affinity of this sub-Arctic species was less affected by temperature than those of living (sub)tropical sea cows. This phenotype presumably safeguarded O2 delivery to cool peripheral tissues and largely arises from a reduced intrinsic temperature sensitivity of the H. gigas protein. Additional experiments on H. gigas β/δ82Asn→Lys mutant Hb further reveal this exchange renders Steller's sea cow Hb unresponsive to the potent intraerythrocytic allosteric effector 2,3-diphosphoglycerate, a radical modification that is the first documented example of this phenotype among mammals. Notably, β/δ82Lys→Asn moreover underlies the secondary evolution of a reduced blood-O2 affinity phenotype that would have promoted heightened tissue and maternal/fetal O2 delivery. This conclusion is bolstered by analyses of two Steller's sea cow prenatal Hb proteins (Hb Gower I; z2e2 and HbF; a2g2) that suggest an exclusive embryonic stage expression pattern, and reveal uncommon replacements in H. gigas HbF (g38Thr→Ile and g101Glu→Asp) that increased Hb-O2 affinity relative to dugong HbF. Finally, the β/δ82Lys→Asn replacement of the adult/fetal protein is shown to increase protein solubility, which may have elevated red blood cell Hb content within both the adult and fetal circulations and contributed to meeting the elevated metabolic (thermoregulatory) requirements and fetal growth rates associated with this species cold adaptation.

Data availability

Source data files for all data presented are provided as Excel files. Accession numbers for previously published nucleotide sequences used in this study are provided in the manuscript and supporting file.

Article and author information

Author details

  1. Anthony V Signore

    Department of Biological Sciences, University of Manitoba, Winnipeg, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0664-0864
  2. Phillip R Morrison

    Department of Zoology, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
  3. Colin J Brauner

    Department of Zoology, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
  4. Angela Fago

    Department of Biology, Aarhus University, Aarhus, Denmark
    Competing interests
    The authors declare that no competing interests exist.
  5. Roy E Weber

    Department of Biology, Aarhus University, Aarhus, Denmark
    Competing interests
    The authors declare that no competing interests exist.
  6. Kevin L Campbell

    Department of Biological Sciences, University of Manitoba, Winnipeg, Canada
    For correspondence
    kevin.campbell@umanitoba.ca
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7005-7086

Funding

Natural Sciences and Engineering Research Council of Canada (RGPIN/238838-2011)

  • Kevin L Campbell

Natural Sciences and Engineering Research Council of Canada (RGPIN/412336-2011)

  • Kevin L Campbell

Natural Sciences and Engineering Research Council of Canada (RGPIN/06562-2016)

  • Kevin L Campbell

Natural Sciences and Engineering Research Council of Canada (RGPIN/261924-2013)

  • Colin J Brauner

Natural Sciences and Engineering Research Council of Canada (RGPIN/446005-2013)

  • Colin J Brauner

Danmarks Frie Forskningsfond (DFF-4181-00094)

  • Angela Fago

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2023, Signore et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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https://doi.org/10.7554/eLife.85414

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