title: Subfunctionalization of cyprinid hypoxia-inducible factors for roles in development and oxygen sensing.
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.
authors: Division of Genetics and Physiology, Department of Biology, University of Turku, FI-20014 Turku, Finland. kalle.rytkonen@yale.edu
authors: Kalle T
authors: KT
authors: Rytkönen
authors: Arash
authors: A
authors: Akbarzadeh
authors: Hamed K
authors: HK
authors: Miandare
authors: Hiroyasu
authors: H
authors: Kamei
authors: Cunming
authors: C
authors: Duan
authors: Erica H
authors: EH
authors: Leder
authors: Tom A
authors: TA
authors: Williams
authors: Mikko
authors: M
authors: Nikinmaa
mesh_terms: D000818:Animals; D019143:Evolution, Molecular; D020440:Gene Duplication; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D016366:Open Reading Frames; D010100:Oxygen / Q000502:physiology; D050436:Regulatory Elements, Transcriptional; D015027:Zebrafish / Q000235:genetics* / Q000254:growth & development
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010100:Oxygen