The longest mitochondrial protein in metazoans is encoded by the male-transmitted mitogenome of the bivalve Scrobicularia plana

Abstract

Cytochrome c oxidase subunit II (COX2) is one of the three mitochondrially encoded proteins of the complex IV of the respiratory chain that catalyses the reduction of oxygen to water. The cox2 gene spans about 690 base pairs in most animal species and produces a protein composed of approximately 230 amino acids. We discovered an extreme departure from this pattern in the male-transmitted mitogenome of the bivalve Scrobicularia plana with doubly uniparental inheritance (DUI) of mitochondrial DNA (mtDNA), which possesses an important in-frame insertion of approximately 4.8 kb in its cox2 gene. This feature—an enlarged male cox2 gene—is found in many species with DUI; the COX2 protein can be up to 420 amino acids long. Through RT-PCRs, immunoassays and comparative genetics, the evolution and functionality of this insertion in S. plana were characterized. The in-frame insertion is conserved among individuals from different populations and bears the signature of purifying selection seemingly indicating maintenance of functionality. Its transcription and translation were confirmed: this gene produces a polypeptide of 1892 amino acids, making it the largest metazoan COX2 protein known to date. We hypothesize that these extreme modifications in the COX2 protein affect the metabolism of mitochondria containing the male-transmitted mtDNA in Scrobicularia plana .

Confirmation of the first intronic sequence in the bivalvian mitochondrial genome of Macoma balthica (Linnaeus, 1758)

“…For example, in theory, the short one could be used most of the time in the mitochondrial energy cycle, and the long one could possibly be used during embryo development as a mitochondrial tagging mechanism. This is highly supported by a recent study on bivalve Scrobicularia plana done by Tassé et al [69]. This clam represents a parallel situation to the one observed here with M. balthica, a long cox2 gene with insertions between domains.…”

“…This is highly supported by a recent study on bivalve Scrobicularia plana done by Tassé et al . [ 69 ]. This clam represents a parallel situation to the one observed here with M. balthica , a long cox2 gene with insertions between domains.…”

“…Unfortunately, the signal for a smaller 32–37 kDa version of the m-cox2 protein was not detected (personal communication). Furthermore, mitochondrial genes are expressed as polycistronic mRNA, so the presence of transcripts containing and lacking introns after excision is expected ( figure 2 ) [ 69 ]. Of course, final proof for the existence of two m-cox2 protein isoforms in M. balthica cannot be reliably answered without proper proteomic studies.…”

ORFanes in mitochondrial genomes of marine polychaetePolydora

“…In male-transmitted mtDNA mitochondrial genomes of bivalves, some standard PCGs are significantly elongated, whereas additional sequences show no homology to any other known sequence (Ghiselli et al 2021). As a result, the size of the corresponding protein is significantly increased (Tassé et al 2022). It is noteworthy that all three ORFane genes are in frame with previous PCGs (Figure S4), although ORFanes 1 and 3 are separated from the upstream proteins by multiple stop codons and tRNAs (Figure 1).…”

ORFans in Mitochondrial Genomes of Marine Polychaete Polydora

“…Additionally, in male-transmitted mtDNA mitochondrial genomes of bivalves, some standard PCGs are significantly elongated, whereas additional sequences show no homology to any other known sequence ( Ghiselli et al 2021 ). As a result, the size of the corresponding protein is significantly increased ( Tassé et al 2022 ).…”