Skip to main content
Log in

Hypoxia-inducible factor-1α in Antarctic notothenioids contains a polyglutamine and glutamic acid insert that varies in length with phylogeny

  • Original Paper
  • Published:
Polar Biology Aims and scope Submit manuscript

Abstract

The long evolution of the Antarctic perciform suborder of Notothenioidei in the icy, oxygen-rich waters of the Southern Ocean may have reduced selective pressure to maintain a hypoxic response. To test this hypothesis, cDNA of the key transcriptional regulator of hypoxic genes, hypoxia-inducible factor-1α (HIF-1α), was sequenced in heart ventricles of the red-blooded notothenioid, Notothenia coriiceps, and the hemoglobinless icefish, Chaenocephalus aceratus. HIF-1α cDNA is 4500 base pairs (bp) long and encodes 755 amino acids in N. coriiceps, and in C. aceratus, HIF-1α is 3576 bp long and encodes 779 amino acids. All functional domains of HIF-1α are highly conserved compared to other teleosts, but HIF-1α contains a polyglutamine/glutamic acid (polyQ/E) insert nine amino acids long in N. coriiceps and 34 amino acids long in C. aceratus. Sequencing of this region in four additional species, representing three families of notothenioids, revealed that the length of the polyQ/E insert varies with phylogeny. Icefishes, the crown family of notothenioids, contain the longest polyQ/E inserts, ranging between 16 and 34 amino acids long, whereas the basal, cold-temperate notothenioid, Eleginops maclovinus, contains a polyQ/E insert only 4 amino acids long. PolyQ/E inserts may affect dimerization of HIF-1α and HIF-1β, HIF-1 translocation into the nucleus and/or DNA binding.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Anttila K, Dhillon RS, Boulding EG, Farrell AP, Glebe BD, Elliott JAK, Wolters WR, Schulte PM (2013) Variation in temperature tolerance among families of Atlantic salmon (Salmo salar) is associated with hypoxia tolerance, ventricle size and myoglobin level. J Exp Biol 216:1183–1190. doi:10.1242/jeb.080556

    Article  CAS  PubMed  Google Scholar 

  • Beers JM, Sidell BD (2011) Thermal tolerance of Antarctic notothenioid fishes correlates with level of circulating hemoglobin. Physiol Biochem Zool 84:353–362. doi:10.1086/660191

    Article  CAS  PubMed  Google Scholar 

  • Berta M, Brahimi-Horn C, Pouyssegur J (2004) Regulation of the hypoxia-inducible factor-1alpha (HIF-1alpha): a breath of fresh air in hypoxia research. J Soc Biol 198:113–120

    Article  CAS  PubMed  Google Scholar 

  • Bilyk KT, Cheng C-HC (2014) RNA-seq analyses of cellular responses to elevated body temperature in the high Antarctic cryopelagic nototheniid fish Pagothenia borchgrevinki. Mar Genom 18:163–171. doi:10.1016/j.margen.2014.06.006

    Article  Google Scholar 

  • Cao Y-B, Chen X-Q, Wang S, Wang Y-X, Du J-Z (2008) Evolution and regulation of the downstream gene of hypoxia-inducible factor-1α in naked carp (Gymnocypris przewalskii) from Lake Qinghai, China. J Mol Evol 67:570–580. doi:10.1007/s00239-008-9175-4

    Article  CAS  PubMed  Google Scholar 

  • Chen Z, Cheng C-HC, Zhang J, Cao L, Chen L, Zhou L, Jin Y, Ye H, Deng C, Dai Z, Xu Q, Hu P, Sun S, Shen Y, Chen L (2008) Transcriptomic and genomic evolution under constant cold in Antarctic notothenioid fish. Proc Natl Acad Sci USA 105:12944–12949. doi:10.1073/pnas.0802432105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Clark TD, Sandblom E, Cox GK, Hinch SG, Farrell AP (2008) Circulatory limits to oxygen supply during an acute temperature increase in the Chinook salmon (Oncorhynchus tshawytscha). Am J Physiol-Regul Integr Comp Physiol 295:R1631–R1639. doi:10.1152/ajpregu.90461.2008

    Article  CAS  PubMed  Google Scholar 

  • Davie PS, Farrell AP (1991) The coronary and luminal circulations of the myocardium of fishes. Can J Zool 69:1993–2001. doi:10.1139/z91-278

    Article  Google Scholar 

  • Detrich HW, Prasad V, Ludueña RF (1987) Cold-stable microtubules from Antarctic fishes contain unique alpha tubulins. J Biol Chem 262:8360–8366

    CAS  PubMed  Google Scholar 

  • Devor DP, Kuhn DE, O’Brien KM, Crockett EL (2016) Hyperoxia does not extend critical thermal maxima (CT max) in white- or red-blooded antarctic notothenioid fishes. Physiol Biochem Zool 89:1–9. doi:10.1086/684812

    Article  PubMed  Google Scholar 

  • DeVries AL, Wohlschlag DE (1969) Freezing resistance in some Antarctic fishes. Science 163:1073–1075

    Article  CAS  PubMed  Google Scholar 

  • Duyao M, Ambrose C, Myers R, Novelletto A, Persichetti F, Frontali M, Folstein S, Ross C, Franz M, Abbott M, Gray J, Conneally P, Young A, Penney J, Hollingsworth Z, Shoulson I, Lazzarini A, Falek A, Koroshetz W, Sax D, Bird E, Vonsattel J, Bonilla E, Alvir J, Bickham Conde J, Cha J-H, Dure L, Gomez F, Ramos M, Sanchez-Ramos J, Snodgrass S, de Young M, Wexler N, Moscowitz C, Penchaszadeh G, MacFarlane H, Anderson M, Jenkins B, Srinidhi J, Barnes G, Gusella J, MacDonald M (1993) Trinucleotide repeat length instability and age of onset in Huntington’s disease. Nat Genet 4:387–392. doi:10.1038/ng0893-387

    Article  CAS  PubMed  Google Scholar 

  • Eastman JT (1993) Antarctic fish biology: evolution in a unique environment. Academic Press, San Diego

    Google Scholar 

  • Eastman JT (2005) The nature of the diversity of Antarctic fishes. Polar Biol 28:93–107. doi:10.1007/s00300-004-0667-4

    Article  Google Scholar 

  • Eliason EJ, Clark TD, Hague MJ, Hanson LM, Gallagher ZS, Jeffries KM, Gale MK, Patterson DA, Hinch SG, Farrell AP (2011) Differences in thermal tolerance among sockeye Salmon populations. Science 332:109–112. doi:10.1126/science.1199158

    Article  CAS  PubMed  Google Scholar 

  • Ely BR, Lovering AT, Horowitz M, Minson CT (2014) Heat acclimation and cross tolerance to hypoxia. Temperature 1:107–114. doi:10.4161/temp.29800

    Article  Google Scholar 

  • Gerber H-P, Seipel K, Georgiev O, Höfferer M, Hug M, Rusconi S, Schaffner W (1994) Transcriptional activation modulated by homopolymeric glutamine and proline stretches. Science 263:808–811. doi:10.1126/science.8303297

    Article  CAS  PubMed  Google Scholar 

  • Gidalevitz T, Ben-Zvi A, Ho KH, Brignull HR, Morimoto RI (2006) Progressive disruption of cellular protein folding in models of polyglutamine diseases. Science 311:1471–1474. doi:10.1126/science.1124514

    Article  CAS  PubMed  Google Scholar 

  • Hofmann GE, Buckley BA, Airaksinen S, Keen JE, Somero GN (2000) Heat-shock protein expression is absent in the Antarctic fish Trematomus bernacchii (family Nototheniidae). J Exp Biol 203:2331–2339

    CAS  PubMed  Google Scholar 

  • Hon W-C, Wilson MI, Harlos K, Claridge TDW, Schofield CJ, Pugh CW, Maxwell PH, Ratcliffe PJ, Stuart DI, Jones EY (2002) Structural basis for the recognition of hydroxyproline in HIF-1α by pVHL. Nature 417:975–978. doi:10.1038/nature00767

    Article  CAS  PubMed  Google Scholar 

  • Hong S-S, Lee H, Kim K-W (2004) HIF-1α: a valid therapeutic target for tumor therapy. Cancer Res Treat 36:343–353. doi:10.4143/crt.2004.36.6.343

    Article  PubMed  PubMed Central  Google Scholar 

  • Huth TJ, Place SP (2013) De novo assembly and characterization of tissue specific transcriptomes in the emerald notothen, Trematomus bernacchii. BMC Genomics 14:805. doi:10.1186/1471-2164-14-805

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huth TJ, Place SP (2016) RNA-seq reveals a diminished acclimation response to the combined effects of ocean acidification and elevated seawater temperature in Pagothenia borchgrevinki. Mar Genom 28:87–97. doi:10.1016/j.margen.2016.02.004

    Article  Google Scholar 

  • Ivan M, Kondo K, Yang H, Kim W, Valiando J, Ohh M, Salic A, Asara JM, Lane WS, Kaelin WG (2001) HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing. Science 292:464–468. doi:10.1126/science.1059817

    Article  CAS  PubMed  Google Scholar 

  • Jaakkola P, Mole DR, Tian Y-M, Wilson MI, Gielbert J, Gaskell SJ, von Kriegsheim A, Hebestreit HF, Mukherji M, Schofield CJ, Maxwell PH, Pugh CW, Ratcliffe PJ (2001) Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science 292:468–472. doi:10.1126/science.1059796

    Article  CAS  PubMed  Google Scholar 

  • Jiang B-H, Zheng JZ, Leung SW, Roe R, Semenza GL (1997) Transactivation and inhibitory domains of hypoxia-inducible factor 1α. Modulation of transcriptional activity by oxygen tension. J Biol Chem 272:19253–19260. doi:10.1074/jbc.272.31.19253

    Article  CAS  PubMed  Google Scholar 

  • Kumar S, Stecher G, Tamura K (2016) MEGA7: molecular evolutionary genetics analysis version 7.0 for bigger datasets. Mol Biol Evol 33:1870–1874. doi:10.1093/molbev/msw054

    Article  CAS  PubMed  Google Scholar 

  • Lando D, Peet DJ, Whelan DA, Gorman JJ, Whitelaw ML (2002) Asparagine hydroxylation of the HIF transactivation domain a hypoxic switch. Science 295:858–861. doi:10.1126/science.1068592

    Article  CAS  PubMed  Google Scholar 

  • Min J-H, Yang H, Ivan M, Gertler F, Kaelin WG, Pavletich NP (2002) Structure of an HIF-1alpha -pVHL complex: hydroxyproline recognition in signaling. Science 296:1886–1889. doi:10.1126/science.1073440

    Article  CAS  PubMed  Google Scholar 

  • Nalavade R, Griesche N, Ryan DP, Hildebrand S, Krauß S (2013) Mechanisms of RNA-induced toxicity in CAG repeat disorders. Cell Death Dis 4:e752. doi:10.1038/cddis.2013.276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Near TJ, Dornburg A, Kuhn KL, Eastman JT, Pennington JN, Patarnello T, Zane L, Fernández DA, Jones CD (2012) Ancient climate change, antifreeze, and the evolutionary diversification of Antarctic fishes. Proc Natl Acad Sci USA 109:3434–3439. doi:10.1073/pnas.1115169109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Podrabsky JE (2004) Changes in gene expression associated with acclimation to constant temperatures and fluctuating daily temperatures in an annual killifish Austrofundulus limnaeus. J Exp Biol 207:2237–2254. doi:10.1242/jeb.01016

    Article  CAS  PubMed  Google Scholar 

  • Römisch K, Collie N, Soto N, Logue J, Lindsay M, Scheper W, Cheng C-HC (2003) Protein translocation across the endoplasmic reticulum membrane in cold-adapted organisms. J Cell Sci 116:2875–2883. doi:10.1242/jcs.00597

    Article  PubMed  Google Scholar 

  • Rost B, Yachdav G, Liu J (2004) The PredictProtein server. Nucl Acids Res 32:W321–W326. doi:10.1093/nar/gkh377

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sandblom E, Clark TD, Gräns A, Ekström A, Brijs J, Sundström LF, Odelström A, Adill A, Aho T, Jutfelt F (2016) Physiological constraints to climate warming in fish follow principles of plastic floors and concrete ceilings. Nat Commun 7:11447. doi:10.1038/ncomms11447

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schaefer MH, Wanker EE, Andrade-Navarro MA (2012) Evolution and function of CAG/polyglutamine repeats in protein-protein interaction networks. Nucl Acids Res 40:4273–4287. doi:10.1093/nar/gks011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Scherzinger E, Lurz R, Turmaine M, Mangiarini L, Hollenbach B, Hasenbank R, Bates GP, Davies SW, Lehrach H, Wanker EE (1997) Huntingtin-encoded polyglutamine expansions form amyloid-like protein aggregates in vitro and in vivo. Cell 90:549–558. doi:10.1016/S0092-8674(00)80514-0

    Article  CAS  PubMed  Google Scholar 

  • Semenza GL (2004) Hydroxylation of HIF-1: oxygen sensing at the molecular level. Physiology 19:176–182. doi:10.1152/physiol.00001.2004

    Article  CAS  PubMed  Google Scholar 

  • Semenza GL, Agani F, Booth G, Forsythe J, Iyer N, Jiang BH, Leung S, Roe R, Wiener C, Yu A (1997) Structural and functional analysis of hypoxia-inducible factor 1. Kidney Int 51:553–555

    Article  CAS  PubMed  Google Scholar 

  • Shin SC, Ahn DH, Kim SJ, Pyo CW, Lee H, Kim M-K, Lee J, Lee JE, Detrich HW, Postlethwait JH, Edwards D, Lee SG, Lee JH, Park H (2014) The genome sequence of the Antarctic bullhead notothen reveals evolutionary adaptations to a cold environment. Genome Biol 15:468. doi:10.1186/s13059-014-0468-1

    Article  PubMed  PubMed Central  Google Scholar 

  • Sidell BD, Vayda ME, Small DJ, Moylan TJ, Londraville RL, Yuan M-L, Rodnick KJ, Eppley ZA, Costello L (1997) Variable expression of myoglobin among the hemoglobinless Antarctic icefishes. Proc Natl Acad Sci USA 94:3420–3424. doi:10.1073/pnas.94.7.3420

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sollid J, Rissanen E, Tranberg HK, Thorstensen T, Vuori KA, Nikinmaa M, Nilsson GE (2006) HIF-1α and iNOS levels in crucian carp gills during hypoxia-induced transformation. J Comp Physiol B Biochem Syst Environ Physiol 176:359–369. doi:10.1007/s00360-005-0059-2

    Article  CAS  Google Scholar 

  • Somero GN, DeVries AL (1967) Temperature tolerance of some Antarctic fishes. Science 156:257–258

    Article  CAS  PubMed  Google Scholar 

  • Tamura K, Nei M (1993) Estimation of the number of nucleotide substitutions in the control region of mitochondrial DNA in humans and chimpanzees. Mol Biol Evol 10:512–526. doi:10.1093/molbev/msl149

    CAS  PubMed  Google Scholar 

  • Treinin M, Shliar J, Jiang H, Powell-Coffman JA, Bromberg Z, Horowitz M (2003) HIF-1 is required for heat acclimation in the nematode Caenorhabditis elegans. Physiol Genomics 14:17–24. doi:10.1152/physiolgenomics.00179.2002

    Article  CAS  PubMed  Google Scholar 

  • Yachdav G, Kloppmann E, Kajan L, Hecht M, Goldberg T, Hamp T, Hönigschmid P, Schafferhans A, Roos M, Bernhofer M, Richter L, Ashkenazy H, Punta M, Schlessinger A, Bromberg Y, Schneider R, Vriend G, Sander C, Ben-Tal N, Rost B (2014) PredictProtein–an open resource for online prediction of protein structural and functional features. Nucl Acids Res 42:W337–W343. doi:10.1093/nar/gku366

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang Z (2007) PAML 4: phylogenetic analysis by maximum likelihood. Mol Biol Evol 24:1586–1591. doi:10.1093/molbev/msm088

    Article  CAS  PubMed  Google Scholar 

  • Zoghbi HY, Orr HT (2000) Glutamine repeats and neurodegeneration. Annu Rev Neurosci 23:217–247. doi:10.1146/annurev.neuro.23.1.217

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Funding was provided by a grant from the National Science Foundation (PLR-1341663 to KOB). A.R. was supported in part by a graduate fellowship from an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health (NIH) (P20GM103395). The content of this work is solely the responsibility of the authors and does not necessarily reflect the official views of the NIH. Thanks to Dr. Chi-Hing Christina Cheng for providing samples of E. maclovinus.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to K. M. O’Brien.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rix, A.S., Grove, T.J. & O’Brien, K.M. Hypoxia-inducible factor-1α in Antarctic notothenioids contains a polyglutamine and glutamic acid insert that varies in length with phylogeny. Polar Biol 40, 2537–2545 (2017). https://doi.org/10.1007/s00300-017-2164-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00300-017-2164-6

Keywords

Navigation