Add time:07/14/2019         Source:sciencedirect.com

Cytochrome B is the mitochondrial protein, which functions as part of the electron transport chain and is the main subunit of transmembrane cytochrome bc1 and b6f complexes affecting energy metabolism through oxidative phosphorylation. The present study was conducted to study the effect of mutation of Cytochrome B gene on the health condition of sheep, which the first report of association of mitochondrial gene with disease traits in livestock species. Non-synonymous substitutions (F33 L and D171N) and Indel mutations were observed for Cytochrome B gene, leading to a truncated protein, where anemia, malfunctioning of most of the vital organs as liver, kidney and mineral status was observed and debility with exercise intolerance and cardiomyopathy in extreme cases were depicted. These findings were confirmed by bioinformatics analysis, haematological and biochemical data analysis, and other phenotypical physiological data pertaining to different vital organs. The molecular mechanism of cytochrome B mutation was that the mutant variant interferes with the site of heme binding (iron containing) domain and calcium binding essential for electron transport chain. Mutation at amino acid site 33 is located within transmembrane helix A, a hydrophobic environment at the Qi site and close to heme binding domain, and mutation effects these domain and diseases occur. Thermodynamic stability was also observed to decrease in mutant variant. Sheep Cytochrome B being genetically more similar to the human, it may be used as a model for studying human diseases related to cytochrome B defects. Future prospect of the study includes the therapeutic application of recombinant protein, gene therapy and marker-assisted selection of disease-resistant livestock.

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