Expression of mitochondrial protein genes encoded by nuclear and mitochondrial genomes correlate with energy metabolism in dairy cattle

Abstract

Background Mutations in the mitochondrial genome have been implicated in mitochondrial disease, often characterised by impaired cellular energy metabolism. Cellular energy metabolism in mitochondria involves mitochondrial proteins (MPs) from both the nuclear ( Nu MP) and mitochondrial ( Mt MP) genomes. The expression of MP genes in tissues may be tissue specific to meet varying specific energy demands across the tissues. Currently, the characteristics of MP gene expression in tissues of dairy cattle are not well understood. In this study, we profile the expression of MP genes in 29 adult and six foetal tissues in dairy cattle using RNA sequencing and gene expression analyses: particularly differential gene expression and co-expression network analyses. Results MP genes were differentially expressed (DE; over-expressed or under-expressed) across tissues in cattle. All 29 tissues showed DE Nu MP genes in varying proportions of over-expression and under-expression. On the other hand, DE of Mt MP genes was observed in <50% of tissues and notably Mt MP genes within a tissue was either all over-expressed or all under-expressed . A high proportion of Nu MP (up to 60%) and Mt MP (up to 100%) genes were over-expressed in tissues with expected high metabolic demand; heart, skeletal muscles and tongue, and under-expressed (up to 45% of Nu MP, 77% of Mt MP genes) in tissues with expected low metabolic rates; leukocytes, thymus, and lymph nodes. These tissues also invariably had the expression of all Mt MP genes in the direction of dominant Nu MP genes expression. The Nu MP and Mt MP genes were highly co-expressed across tissues and co-expression of genes in a cluster were non-random and functionally enriched for energy generation pathways. The differential gene expression and co-expression patterns were validated in independent cow and sheep datasets. Conclusions This study demonstrated the biological interaction of MP genes from the mitochondrial and nuclear genomes and their over-expression in tissues with high energy demand. This highlights the importance of considering MP genes from both genomes in future studies related to mitochondrial functions and traits related to energy metabolism.