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Low dissolved oxygen (hypoxia) poses significant challenges to aquatic ecosystems, affecting the behavior, reproduction, and survival of aquatic organisms. Some fishes respond to hypoxia by changes in gene expression, which may be regulated by the hypoxia inducible factor (HIF) family of transcription factors. HIF abundance and activity depends upon the post-translational modification of the alpha protein subunit, although several studies indicate that HIFA mRNA abundance increases in tissues of fishes exposed to hypoxia. This study reviewed reports of laboratory exposures of adult ray-finned fishes to hypoxia and used generalized linear mixed effects models to examine the influence of HIFA gene, tissue sampled, and exposure conditions in explaining the diversity of responses seen in HIFA mRNA abundance. The frequency of hypoxia-induced increases in HIFA mRNA was poorly explained by gene, tissue, or the severity of the hypoxic exposure. Rather, the frequency of reported increases was strongly related to the extent to which studies adhered to guidelines for documenting quantitative real-time PCR methods: the frequency of hypoxia-induced increases in HIFA mRNA decreased sharply in studies with more thorough description of experimental design. Future research should (a) adhere to stringent reporting of experimental design, (b) address the relative paucity of data on HIF2A and HIF3A , and (c) determine levels of HIF alpha protein subunits. By following these recommendations, it is hoped that a more complete understanding will be gained of the role of the HIF family of transcription factors in the response of fish to hypoxia. [ABSTRACT FROM AUTHOR]

Low dissolved oxygen (hypoxia) is recognized as a major threat to aquatic ecosystems worldwide. Because oxygen is paramount for the energy metabolism of animals, understanding the functional and genetic drivers of whole-animal hypoxia tolerance is critical to predicting the impacts of aquatic hypoxia. In this study, we investigate the molecular evolution of key genes involved in the detection of and response to hypoxia in ray-finned fishes: the prolyl hydroxylase domain (PHD)–hypoxia-inducible factor (HIF) oxygen-sensing system, also known as the EGLN (egg-laying nine)– HIF oxygen-sensing system. We searched fish genomes for HIFA and EGLN genes, discovered new paralogs from both gene families, and analyzed protein-coding sites under positive selection. The physicochemical properties of these positively selected amino acid sites were summarized using linear discriminants for each gene. We employed phylogenetic generalized least squares to assess the relationship between these linear discriminants for each HIFA and EGLN and hypoxia tolerance as reflected by the critical oxygen tension (P crit) of the corresponding species. Our results demonstrate that P crit in ray-finned fishes correlates with the physicochemical variation of positively selected sites in specific HIFA and EGLN genes. For HIF2A , two linear discriminants captured more than 90% of the physicochemical variation of these sites and explained between 20% and 39% of the variation in P crit. Thus, variation in HIF2A among fishes may contribute to their capacity to cope with aquatic hypoxia, similar to its proposed role in conferring tolerance to high-altitude hypoxia in certain lineages of terrestrial vertebrates. [ABSTRACT FROM AUTHOR]

As aquatic hypoxia worsens on a global scale, fishes will become increasingly challenged by low oxygen, and understanding the molecular basis of their response to hypoxia may help to better define the capacity of fishes to cope with this challenge. The hypoxia inducible factor (HIF) plays a critical role in the molecular response to hypoxia by activating the transcription of genes that serve to improve oxygen delivery to the tissues or enhance the capacity of tissues to function at low oxygen. The current study examines the molecular evolution of genes encoding the oxygen-dependent HIFα subunit (HIFA) in the ray-finned fishes (Actinopterygii). Genomic analyses demonstrate that several lineages retain four paralogs of HIFA predicted from two rounds of genome duplication at the base of vertebrate evolution, broaden the known distribution of teleost-specific HIFA paralogs, and provide evidence for salmonid-specific HIFA duplicates. Evolution of the HIFA gene family is characterized by widespread episodic positive selection at amino acid sites that potentially mediate protein stability, protein–protein interactions, and transcriptional regulation. HIFA transcript abundance depends upon paralog, tissue, and fish lineage. A phylogenetically-informed gene nomenclature is proposed along with avenues for future research on this critical family of transcription factors. [ABSTRACT FROM AUTHOR]