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      Hypoxia Inducible Factor (HIF) transcription factor family expansion, diversification, divergence and selection in eukaryotes

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      PLoS ONE
      Public Library of Science

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          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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          Most cited references49

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          The recent literature on profile hidden Markov model (profile HMM) methods and software is reviewed. Profile HMMs turn a multiple sequence alignment into a position-specific scoring system suitable for searching databases for remotely homologous sequences. Profile HMM analyses complement standard pairwise comparison methods for large-scale sequence analysis. Several software implementations and two large libraries of profile HMMs of common protein domains are available. HMM methods performed comparably to threading methods in the CASP2 structure prediction exercise.
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            ProtTest: selection of best-fit models of protein evolution.

            Using an appropriate model of amino acid replacement is very important for the study of protein evolution and phylogenetic inference. We have built a tool for the selection of the best-fit model of evolution, among a set of candidate models, for a given protein sequence alignment. ProtTest is available under the GNU license from http://darwin.uvigo.es
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                14 June 2017
                2017
                : 12
                : 6
                : e0179545
                Affiliations
                [001]Department of Biology, University of Miami, Coral Gables, Florida, United States of America
                Laboratoire Oceanologique de Banyuls sur Mer, FRANCE
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: AMG JSP.

                • Data curation: AMG JSP.

                • Formal analysis: AMG JSP.

                • Investigation: AMG JSP.

                • Methodology: AMG JSP.

                • Software: AMG JSP.

                • Visualization: AMG JSP.

                • Writing – original draft: AMG JSP.

                • Writing – review & editing: AMG JSP.

                Author information
                http://orcid.org/0000-0001-7404-168X
                Article
                PONE-D-16-39812
                10.1371/journal.pone.0179545
                5470732
                28614393
                fe6ba7ee-e932-4d52-a9e1-5ac5dcd2e1f9
                © 2017 Graham, Presnell

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 5 October 2016
                : 31 May 2017
                Page count
                Figures: 3, Tables: 1, Pages: 15
                Funding
                The authors received no specific funding for this work.
                Categories
                Research Article
                Biology and Life Sciences
                Organisms
                Animals
                Vertebrates
                Biology and Life Sciences
                Biochemistry
                Proteins
                Protein Domains
                Biology and Life Sciences
                Genetics
                Genomics
                Animal Genomics
                Invertebrate Genomics
                Biology and Life Sciences
                Organisms
                Animals
                Invertebrates
                Biology and Life Sciences
                Evolutionary Biology
                Evolutionary Genetics
                Biology and Life Sciences
                Biochemistry
                Proteins
                Protein Domains
                Basic Helix-Loop-Helix Domain
                Biology and life sciences
                Biochemistry
                Proteins
                DNA-binding proteins
                Research and Analysis Methods
                Database and Informatics Methods
                Bioinformatics
                Sequence Analysis
                Sequence Alignment
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

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                Uncategorized

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