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Predictable convergence in hemoglobin function has unpredictable molecular underpinnings

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Science  21 Oct 2016:
Vol. 354, Issue 6310, pp. 336-339
DOI: 10.1126/science.aaf9070
  • Fig. 1 Amino acid differences that distinguish the Hbs of each pair of high- and low-altitude taxa.

    Derived (nonancestral) amino acids are shown in red lettering, and rows corresponding to high-altitude taxa are shaded in blue. Subunits of the major HbA isoform are encoded by the αA- and βA-globin genes, whereas those of the minor HbD isoform are encoded by the αD- and βA-globin genes. Phylogenetically replicated β-chain replacements that contribute to convergent increases in Hb-O2 affinity (N/G83S, A86S, D94E, and A116S) are outlined. Single-letter abbreviations for the amino acid residues are as follows: A, Ala; C, Cys; D, Asp; E, Glu; F, Phe; G, Gly; H, His; I, Ile; K, Lys; L, Leu; M, Met; N, Asn; P, Pro; Q, Gln; R, Arg; S, Ser; T, Thr; V, Val; and Y, Tyr.

  • Fig. 2 Convergent increases in Hb-O2 affinity in high-altitude Andean birds.

    (A) Plot of P50(KCl+IHP) (± 1 SE) for HbA in 28 matched pairs of high- and low-altitude taxa. Data points that fall below the diagonal line (x = y) denote cases in which the high-altitude member of a given taxon pair possesses a higher Hb-O2 affinity (lower P50). Comparisons involve replicated pairs of taxa, so all data points are phylogenetically independent. (B) Plot of P50(KCl+IHP) (± 1 SE) for the minor HbD isoform in a subset of the same taxon pairs in which both members of the pair express HbD. P50(KCl+IHP), O2 partial pressure at which Hb is 50% saturated in the presence of chloride and inositol hexaphosphate.

  • Fig. 3 Phenotypic effects of substitutions at β83 are conditional on genetic background.

    (A) The engineered G83S mutation produced a significant reduction in P50(KCl+IHP) (increase in Hb-O2 affinity) in the reconstructed Hb of the hummingbird ancestor. (B) The engineered A67V and N83S mutations produced additive reductions in P50(KCl+IHP) in the reconstructed Hb of the flowerpiercer ancestor. Underlining indicates derived (nonancestral) amino acids. (C) Diagrammatic tree with time-scaled branch lengths showing internal nodes that we targeted for ancestral protein resurrection. Scale bar, 10 million years. (D) N/G83S mutations produced significant increases in Hb-O2 affinity (expressed as reductions in P50(KCl+IHP)) in the ancestors of hummingbirds and flowerpiercers. Substitutions at the same site produced no detectable effects in Anc Neoaves or Anc Neornithes.

Supplementary Materials

  • Predictable convergence in hemoglobin function has unpredictable molecular underpinnings

    Chandrasekhar Natarajan, Federico G. Hoffmann, Roy E. Weber, Angela Fago, Christopher C. Witt, Jay F. Storz

    Materials/Methods, Supplementary Text, Tables, Figures, and/or References

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    • Materials and Methods
    • Figs. S1 to S9
    • Tables S1 to S6
    • References

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