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

  title={Substitutions in woolly mammoth hemoglobin confer biochemical properties adaptive for cold tolerance},
  author={Kevin L. Campbell and Jason Roberts and Laura N. Watson and J{\"o}rg Stetefeld and Angela M Sloan and Anthony V. Signore and Jesse W Howatt and Jeremy R. H. Tame and Nadin Rohland and T J Shen and Jeremy J. Austin and Michael Hofreiter and Chien Ho and Roy E. Weber and Alan Cooper},
  journal={Nature Genetics},
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… 
Emergence of a Chimeric Globin Pseudogene and Increased Hemoglobin Oxygen Affinity Underlie the Evolution of Aquatic Specializations in Sirenia
Analysis of the globin repertoire of the extinct Steller’s sea cow, dugong, and Florida manatee in relation to their closest living terrestrial relatives indicates most loci experienced elevated nucleotide substitution rates during their transition to a fully aquatic lifestyle, and indicates this trait evolved to maximize O2 extraction from finite lung stores and suppress tissue O2 offloading.
Structures of haemoglobin from woolly mammoth in liganded and unliganded states.
These models, which are the first structures of Hb from an extinct species, show many features reminiscent of human Hb, but underline how the delicate control of oxygen affinity relies on much more than simple overall quaternary-structure changes.
Elephantid genomes reveal the molecular bases of Woolly Mammoth adaptations to the arctic
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Signals of positive selection in mitochondrial protein‐coding genes of woolly mammoth: Adaptation to extreme environments?
Abstract The mammoths originated in warm and equatorial Africa and later colonized cold and high‐latitude environments. Studies on nuclear genes suggest that woolly mammoth had evolved genetic
A biochemical--biophysical study of hemoglobins from woolly mammoth, Asian elephant, and humans.
It is shown that the four Hbs exhibit distinct structural properties and respond differently to allosteric effectors, suggesting that the oxygen affinity of mammoth blood was also less sensitive to temperature change.
Evolution of Hemoglobin Genes in Codfishes Influenced by Ocean Depth
The results suggest that the more variable environment in shallower water has led to selection for a larger Hb gene repertoire and that Hbs have a key role in adaptive processes in marine environments.
Resurrecting phenotypes from ancient DNA sequences: promises and perspectives
Anatomical changes in extinct mammalian lineages over evolutionary time, such as the loss of fingers and teeth and the rapid increase in body size that accompanied the late Miocene dispersal of Steller’s sea cows, are prime examples of adaptive evolution underlying the exploitation of new habitats.
Evolutionary adaptation revealed by comparative genome analysis of woolly mammoths and elephants
The analysis was extended to systematically identify not only SNVs but also larger structural variants (SVs) and indels and found multiple mammoth-specific deletions and duplications affecting exons or even complete genes.
Origin and mechanism of thermal insensitivity in mole hemoglobins: a test of the ‘additional’ chloride binding site hypothesis
It is demonstrated that the numerically low ΔH′ of coast and eastern mole Hbs results from heightened proton binding relative to other mole Hb, as the Cl– sensitivity of mole HBS is unaffected by amino acid changes at this site (i.e. the proposed ‘additional’ Cl– binding site is not operational in Mole Hbs).


Species adaptation in a protein molecule.
  • M. Perutz
  • Biology
    Molecular biology and evolution
  • 1983
The results indicate that the tertiary and quaternary structures of deoxy- and oxyhemoglobin have remained almost invariant during vertebrate evolution and that most of the amino acid replacements between species are functionally neutral.
Mutagenic dissection of hemoglobin cooperativity: Effects of amino acidalteration on subunit assembly of oxy and deoxy tetramers
The current data base provides a unique framework for further analyses and modeling of fundamental issues in the structural chemistry of proteins and allosteric mechanisms, and shows that the α1 β2 interface is a unique structural location of the noncovalent bonding interactions that are energetically coupled to cooperativity.
Sequencing the nuclear genome of the extinct woolly mammoth
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The presence of a chimeric beta/delta fusion gene in the African elephant that was created by unequal crossing-over between misaligned HBD and HBB paralogs is reported, illustrating how the evolutionary fates of chimeric fusion genes can be strongly influenced by their recombinational mode of origin.
Reconstructing the evolutionary history of the artiodactyl ribonuclease superfamily
This work suggests that contemporary artiodactyl digestive RNases arose from a non-digestive ancestor, and illustrates how evolutionary reconstructions can help in the understanding of physiological function within a protein family.
From the Arctic to fetal life: physiological importance and structural basis of an 'additional' chloride-binding site in haemoglobin.
It is shown that binding of extra chloride ions to Hb would significantly contribute to lowering the overall heat of oxygenation, thus providing a molecular basis for the low effect of temperature on the oxygenation-deoxygenation cycle.
Allosteric Modulation by Tertiary Structure in Mammalian Hemoglobins
Two mutant human hemoglobins are constructed and Oxygen binding studies demonstrate that these mutations have introduced into human hemoglobin the low oxygen affinity and chloride sensitivity of bovine hemoglobin and reveal the presence of a previously unrecognized allosteric mechanism of oxygen affinity regulation.
Proboscidean Mitogenomics: Chronology and Mode of Elephant Evolution Using Mastodon as Outgroup
The complete mitochondrial genome of the extinct American mastodon is sequenced from an Alaskan fossil that is between 50,000 and 130,000 y old, extending the age range of genomic analyses by almost a complete glacial cycle and concluding that the first sequence of mastodon DNA ever reported is obtained.
Hemoglobin function under extreme life conditions.
A thermodynamic analysis of oxygen binding with hemoglobins from different species reveals a series of adaptive mechanisms which are based on the thermodynamic connection between the binding of heterotropic effectors and the reaction with oxygen.