Journal
GENE
Volume 420, Issue 1, Pages 1-10Publisher
ELSEVIER
DOI: 10.1016/j.gene.2008.04.018
Keywords
oxygen; vertebrates; transcription factor; bHLH-PAS; negative selection; positive selection
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The hypoxia-inducible factor-1 alpha (HIF-1 alpha) protein is the major regulator of oxygen-dependent gene expression and a member of the bHLH-PAS family of transcription factors. In this study we compared and contrasted the rate and mode of HIF-1 alpha molecular evolution between teleost fishes and mammals, as well as within teleost fishes and mammals. Various likelihood methods for estimating codon substitutions were used to detect different modes of selection. Although the overall evolutionary rate in teleost HIF-1 alpha was atleast twice as fast as in mammalian HIF-1 alpha compared to mammalian HIF-1 alpha was detected, but no evidence for positive selection that was supported by all methods was found. We suggest that the relaxed selective constraints in teleost HIF-1 alpha may be associated with the variable environmental oxygen levels to which teleosts have been exposed during their evolutionary history. However, in teleosts the positions with partial support for positive selection were not found in the vicinity of the HIF-1 alpha domains which confer the oxygen sensitivity, but in the bHLH-PAS domain responsible for DNA binding and dimerization. The pattern of selection in the bHLH-PAS domain has some similarities with the patterns observed in the adaptive evolution of the homeodomain of Hox genes and may be typical in the molecular evolution of transcription factors. (C) Elsevier B.V. All rights reserved.
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