Probable presence of an ubiquitous cryptic mitochondrial gene on the antisense strand of the cytochrome oxidase I gene
Résumé
Background: Mitochondria mediate most of the energy production that occurs in the majority of eukaryotic
organisms. These subcellular organelles contain a genome that differs from the nuclear genome and is referred to
as mitochondrial DNA (mtDNA). Despite a disparity in gene content, all mtDNAs encode at least two components
of the mitochondrial electron transport chain, including cytochrome c oxidase I (Cox1).
Presentation of the hypothesis: A positionally conserved ORF has been found on the complementary strand of the
cox1 genes of both eukaryotic mitochondria (protist, plant, fungal and animal) and alpha-proteobacteria. This putative
gene has been named gau for gene antisense ubiquitous in mtDNAs. The length of the deduced protein is
approximately 100 amino acids. In vertebrates, several stop codons have been found in the mt gau region, and
potentially functional gau regions have been found in nuclear genomes. However, a recent bioinformatics study
showed that several hypothetical overlapping mt genes could be predicted, including gau; this involves the possible
import of the cytosolic AGR tRNA into the mitochondria and/or the expression of mt antisense tRNAs with anticodons
recognizing AGR codons according to an alternative genetic code that is induced by the presence of suppressor tRNAs.
Despite an evolutionary distance of at least 1.5 to 2.0 billion years, the deduced Gau proteins share some conserved
amino acid signatures and structure, which suggests a possible conserved function. Moreover, BLAST analysis identified
rare, sense-oriented ESTs with poly(A) tails that include the entire gau region. Immunohistochemical analyses using an
anti-Gau monoclonal antibody revealed strict co-localization of Gau proteins and a mitochondrial marker.
Testing the hypothesis: This hypothesis could be tested by purifying the gau gene product and determining its
sequence. Cell biological experiments are needed to determine the physiological role of this protein.
Implications of the hypothesis: Studies of the gau ORF will shed light on the origin of novel genes and their
functions in organelles and could also have medical implications for human diseases that are caused by
mitochondrial dysfunction. Moreover, this strengthens evidence for mitochondrial genes coded according to an
overlapping genetic code.
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