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Evolution of the Cytochrome c Oxidase Subunit 4 Paralogs
Author(s) -
Moyes Christopher D,
Porplycia Danielle,
McDonald Jared
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.979.5
Subject(s) - biology , biochemistry , cytochrome c oxidase , hypoxia (environmental) , microbiology and biotechnology , chemistry , mitochondrion , oxygen , organic chemistry
The largest subunit of cytochrome c oxidase exists as two paralogs in most vertebrates: a constitutive COX4‐1 and hypoxia‐inducible COX4‐2. In primates and rodents, COX4‐2 is a hypoxia‐responsive gene encoding a protein with its ATP‐binding site disrupted by a disulfide bridge, precluding COX from the allosteric regulation that is exerted through the this site in COX4‐1. In an effort to understand the evolution of the gene, we examined role of the paralogs in fish. COX4‐2 of fish differs from mammals in three respects. First, the fish COX4‐2 gene does not appear to be hypoxia responsive at either the mRNA or protein level. This was shown in mammalian cells transfected with fish promoter constructs, and hypoxia treatments of cultured fish cells and whole animals. We used fish species from multiple lineages and differing in hypoxia tolerance, exposed to different degrees and durations of low oxygen. Second, the fish COX4‐2 protein lacks the structural features (paired CYS residues) that distinguish COX4‐2 from COX4‐1 in mammals. This pair of CYS residues in COX4‐2 protein appears only in the lineage of vertebrates that encompasses rodents and primates. Third, COX4‐2 expression patterns are quite different in fish. They show higher constitutive expression of COX4‐2 in all tissues, and demonstrate changes in COX4‐2 expression with development. Immunohistochemistry of tissues expressing both COX4 paralogs revealed that some tissues displayed both proteins in most cells, whereas other tissues showed cell‐specific patterns. In heart, individual myocytes expressed both COX4 paralogs, although select non‐myocytes expressed only COX4‐1. The paralog patterns also changed with size/age. Heart was dominated by COX4‐1 mRNA and protein in small fish but transitioned to predominately mRNA and COX4‐2 in large fish. The distinctions in COX4‐2 between mammalian models (rodents, humans) and other vertebrates (other mammalian lineages, reptiles, fish) bring into question the genetic origins of the paralog pair and its functional evolution during vertebrate diversification. Support or Funding Information Supported by NSERC Canada