Recurrent erosion ofCOA1/MITRAC15demonstrates gene dispensability in oxidative phosphorylation

Abstract

Skeletal muscle fibers rely upon either oxidative phosphorylation or glycolytic pathway to achieve muscular contractions that power mechanical movements. Species with energy-intensive adaptive traits that require sudden bursts of energy have a greater dependency on fibers that use the glycolytic pathway. Glycolytic fibers have decreased reliance on OXPHOS and lower mitochondrial content compared to oxidative fibers. Hence, we hypothesized that adaptive gene loss might have occurred within the OXPHOS pathway in lineages that largely depend on glycolytic fibers. The protein encoded by the COA1/MITRAC15 gene with conserved orthologs found in budding yeast to humans promotes mitochondrial translation. We show that gene disrupting mutations have accumulated within the COA1/MITRAC15 gene in the cheetah, several species of galliforms, and rodents. The genomic region containing COA1/MITRAC15 is a well-established evolutionary breakpoint region in mammals. Careful inspection of genome assemblies of closely related species of rodents and marsupials suggests two independent COA1/MITRAC15 gene loss events co-occurring with chromosomal rearrangements. Besides recurrent gene loss events, we document changes in COA1/MITRAC15 exon structure in primates and felids. The detailed evolutionary history presented in this study reveals the intricate link between skeletal muscle fiber composition and dispensability of the chaperone-like role of the COA1/MITRAC15 gene.

Sideroflexin 4 is a complex I assembly factor that interacts with the MCIA complex and is required for the assembly of the ND2 module

“…It is important to note that SFXN4 is not absolutely required for complex I biogenesis, as some complex I is able to assemble in its absence, and patients with homozygous loss-of-function mutations in SFXN4 are able to live into at least early adolescence ( 7 , 8 ). It will be interesting to determine when SFXN4 emerged as a complex I assembly factor from an evolutionary perspective and whether its role is conserved in some lineages and lost in others, as a recent study demonstrated has occurred for COA1 ( 29 ).…”