ArticlePloS one2017
Hypoxia Inducible Factor (HIF) transcription factor family expansion, diversification, divergence and selection in eukaryotes.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 108 citations in OpenAlex.
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- Hypoxia Disrupts Sex-Specific Physiology and Gene Expression Leading to Decreased Fitness in the Estuarine Sea Anemone Nematostella vectensis.Molecular ecology · 2025Article
- Selection Pressure Regulates the Evolution-Structure-Function Paradigm of Monocyte Chemoattractant Protein Family.Journal of molecular evolution · 2025Article
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- Identification of novel potential hypoxia-inducible factor-1α inhibitors through machine learning and computational simulations.Frontiers in chemistry · 2025Article
- Transformative Impact of Nanocarrier-Mediated Drug Delivery: Overcoming Biological Barriers and Expanding Therapeutic Horizons.Small science · 2024Article
- Evolution of Key Oxygen-Sensing Genes Is Associated with Hypoxia Tolerance in Fishes.Genome biology and evolution · 2024Article
- Article
- Hypoxia-induced pulmonary hypertension in adults and newborns: implications for drug development.Drug discovery today · 2024Review
- The strict regulation of HIF-1α by non-coding RNAs: new insight towards proliferation, metastasis, and therapeutic resistance strategies.Cancer metastasis reviews · 2024Review
- Evolution of the Major Components of Innate Immunity in Animals.Journal of molecular evolution · 2024Review
- Targeting Hypoxia-Inducible Factor-1 (HIF-1) in Cancer: Emerging Therapeutic Strategies and Pathway Regulation.Pharmaceuticals (Basel, Switzerland) · 2024Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia inducible factor (HIF) transcription factors are crucial for regulating a variety of cellular activities in response to oxygen stress (hypoxia). In this study, we determine the evolutionary history of HIF genes and their associated transactivation domains, as well as perform selection and functional divergence analyses across their four characteristic domains. Here we show that the HIF genes are restricted to metazoans: At least one HIF-α homolog is found within the genomes of non-bilaterians and bilaterian invertebrates, while most vertebrate genomes contain between two and six HIF-α genes. We also find widespread purifying selection across all four characteristic domain types, bHLH, PAS, NTAD, CTAD, in HIF-α genes, and evidence for Type I functional divergence between HIF-1α, HIF-2α /EPAS, and invertebrate HIF genes. Overall, we describe the evolutionary histories of the HIF transcription factor gene family and its associated transactivation domains in eukaryotes. We show that the NTAD and CTAD domains appear de novo, without any appearance outside of the HIF-α subunits. Although they both appear in invertebrates as well as vertebrate HIF- α sequences, there seems to have been a substantial loss across invertebrates or were convergently acquired in these few lineages. We reaffirm that HIF-1α is phylogenetically conserved among most metazoans, whereas HIF-2α appeared later. Overall, our findings can be attributed to the substantial integration of this transcription factor family into the critical tasks associated with maintenance of oxygen homeostasis and vascularization, particularly in the vertebrate lineage.
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