Molecular basis of hemoglobin adaptation in the high-flying bar-headed goose

Chandrasekhar Natarajan, Agnieszka Jendroszek, Amit Kumar, Roy E. Weber, Jeremy R.H. Tame, Angela Fago, Jay F Storz

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

During the adaptive evolution of a particular trait, some selectively fixed mutations may be directly causative and others may be purely compensatory. The relative contribution of these two classes of mutation to adaptive phenotypic evolution depends on the form and prevalence of mutational pleiotropy. To investigate the nature of adaptive substitutions and their pleiotropic effects, we used a protein engineering approach to characterize the molecular basis of hemoglobin (Hb) adaptation in the high-flying bar-headed goose (Anser indicus), a hypoxia-tolerant species renowned for its trans-Himalayan migratory flights. To test the effects of observed substitutions on evolutionarily relevant genetic backgrounds, we synthesized all possible genotypic intermediates in the line of descent connecting the wildtype bar-headed goose genotype with the most recent common ancestor of bar-headed goose and its lowland relatives. Site-directed mutagenesis experiments revealed one major-effect mutation that significantly increased Hb-O2affinity on all possible genetic backgrounds. Two other mutations exhibited smaller average effect sizes and less additivity across backgrounds. One of the latter mutations produced a concomitant increase in the autoxidation rate, a deleterious side-effect that was fully compensated by a second-site mutation at a spatially proximal residue. The experiments revealed three key insights: (i) subtle, localized structural changes can produce large functional effects; (ii) relative effect sizes of function-altering mutations may depend on the sequential order in which they occur; and (iii) compensation of deleterious pleiotropic effects may play an important role in the adaptive evolution of protein function.

Original languageEnglish (US)
Article numbere1007331
JournalPLoS genetics
Volume14
Issue number4
DOIs
StatePublished - Apr 1 2018

Fingerprint

Geese
hemoglobin
mutation
Hemoglobins
flight
Mutation
genetic background
substitution
protein engineering
pleiotropy
Protein Engineering
protein
autoxidation
site-directed mutagenesis
common ancestry
hypoxia
Site-Directed Mutagenesis
Anser indicus
effect
structural change

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

Cite this

Natarajan, C., Jendroszek, A., Kumar, A., Weber, R. E., Tame, J. R. H., Fago, A., & Storz, J. F. (2018). Molecular basis of hemoglobin adaptation in the high-flying bar-headed goose. PLoS genetics, 14(4), [e1007331]. https://doi.org/10.1371/journal.pgen.1007331

Molecular basis of hemoglobin adaptation in the high-flying bar-headed goose. / Natarajan, Chandrasekhar; Jendroszek, Agnieszka; Kumar, Amit; Weber, Roy E.; Tame, Jeremy R.H.; Fago, Angela; Storz, Jay F.

In: PLoS genetics, Vol. 14, No. 4, e1007331, 01.04.2018.

Research output: Contribution to journalArticle

Natarajan, C, Jendroszek, A, Kumar, A, Weber, RE, Tame, JRH, Fago, A & Storz, JF 2018, 'Molecular basis of hemoglobin adaptation in the high-flying bar-headed goose', PLoS genetics, vol. 14, no. 4, e1007331. https://doi.org/10.1371/journal.pgen.1007331
Natarajan C, Jendroszek A, Kumar A, Weber RE, Tame JRH, Fago A et al. Molecular basis of hemoglobin adaptation in the high-flying bar-headed goose. PLoS genetics. 2018 Apr 1;14(4). e1007331. https://doi.org/10.1371/journal.pgen.1007331
Natarajan, Chandrasekhar ; Jendroszek, Agnieszka ; Kumar, Amit ; Weber, Roy E. ; Tame, Jeremy R.H. ; Fago, Angela ; Storz, Jay F. / Molecular basis of hemoglobin adaptation in the high-flying bar-headed goose. In: PLoS genetics. 2018 ; Vol. 14, No. 4.
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