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SUBFUNCTIONALIZATION OF CYPRINID HYPOXIA-INDUCIBLE FACTORS FOR ROLES IN DEVELOPMENT AND OXYGEN SENSING

Authors

  • Kalle T. Rytkönen,

    1. Division of Genetics and Physiology, Department of Biology, University of Turku, FI-20014 Turku, Finland
    2. Current Address: Department of Ecology and Evolutionary Biology, Yale Systems Biology Institute, Yale University, 300 Heffernan Drive, West Haven, Connecticut 06516
    3. E-mail: kalle.rytkonen@yale.edu
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  • Arash Akbarzadeh,

    1. Division of Genetics and Physiology, Department of Biology, University of Turku, FI-20014 Turku, Finland
    2. Department of Fisheries, Faculty of Agriculture and Natural Resources, University of Hormozgan, 3995 Bandar Abbas, Iran
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  • Hamed K. Miandare,

    1. Division of Genetics and Physiology, Department of Biology, University of Turku, FI-20014 Turku, Finland
    2. Department of Fishery, Gorgan University of Agricultural Sciences and Natural Resources, Gorgan 4917638585, Iran
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  • Hiroyasu Kamei,

    1. Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109-1048
    2. Current Address: Departments of Animal Sciences and Applied Biological Chemistry, University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan
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  • Cunming Duan,

    1. Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109-1048
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  • Erica H. Leder,

    1. Division of Genetics and Physiology, Department of Biology, University of Turku, FI-20014 Turku, Finland
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  • Tom A. Williams,

    1. Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE2 4HH, United Kingdom
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  • Mikko Nikinmaa

    1. Division of Genetics and Physiology, Department of Biology, University of Turku, FI-20014 Turku, Finland
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Abstract

Among vertebrates, teleost fishes have evolved the most impressive adaptations to variable oxygen tensions in water (Shoubridge and Hochachka 1980; Nilsson and Randall 2010). Under conditions of oxygen deprivation (hypoxia), major changes in gene expression are mediated by hypoxia-inducible factors (HIF alpha). Here we show that hif alpha genes were duplicated in the teleost specific whole-genome duplication. Although one of each paralogous gene pair was lost in most teleosts, both copies were retained in cyprinids. Computational analyses suggest that these duplicates have become subfunctionalized with complementary changes in coding and regulatory sequences within each paralogous gene pair. We tested our predictions with comparisons of hif alpha transcription in zebrafish, a cyprinid, and sturgeon, an outgroup that diverged from teleosts before the duplication event. Our experiments revealed distinct transcriptional profiles in the cyprinid duplicates: while one of each paralogous pair maintained the ancestral developmental response, the other was more sensitive to changes in oxygen tension. These results demonstrate the subfunctionalization of cyprinid hif alpha paralogs for specialized roles in development and the hypoxic stress response.

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