gene expression patterns of oxidative phosphorylation complex i subunits are organized in clusters基因表达模式的氧化磷酸化复杂我子单元组织集群.pdfVIP

Gene Expression Patterns of Oxidative Phosphorylation Complex I Subunits Are Organized in Clusters 1,2 1 1,2 1,2 Yael Garbian , Ofer Ovadia , Sarah Dadon , Dan Mishmar * 1 Department of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel, 2 National Institute of Biotechnology (NIBN), Ben-Gurion University of the Negev, Beer-Sheva, Israel Abstract After the radiation of eukaryotes, the NUO operon, controlling the transcription of the NADH dehydrogenase complex of the oxidative phosphorylation system (OXPHOS complex I), was broken down and genes encoding this protein complex were dispersed across the nuclear genome. Seven genes, however, were retained in the genome of the mitochondrion, the ancient symbiote of eukaryotes. This division, in combination with the three-fold increase in subunit number from bacteria (N = ,14) to man (N = 45), renders the transcription regulation of OXPHOS complex I a challenge. Recently bioinformatics analysis of the promoter regions of all OXPHOS genes in mammals supported patterns of co-regulation, suggesting that natural selection favored a mechanism facilitating the transcriptional regulatory control of genes encoding subunits of these large protein complexes. Here, using real time PCR of mitochondrial (mtDNA)- and nuclear DNA (nDNA)-encoded transcripts in a panel of 13 different human tissues, we show that the expression pattern of OXPHOS complex I genes is regulated in several clusters. Firstly, all mtDNA-encoded complex I subunits (N = 7) share a similar expression pattern, distinct from all tested nDNA-encoded subunits (N = 10). Secondly, two sub-clusters of nDNA-encoded transcripts with significantly different expression patterns were observed. Thirdly, the expression patterns of two nDNA-encoded genes,