BGU researchers have shown that certain genotype combinations of the mitochondrial and nuclear genomes, but not each genome alone, alter the susceptibility to develop type 2 diabetes. Prof. Dan Mishmar (pictured left) and his colleagues published their findings recently in Genome Biology and Evolution.
“One of the major research projects in my lab focuses on investigating the functional importance of the interaction between the mitochondrial and nuclear genomes for health, disease and evolution,” says Mishmar of the Department of Life Sciences. In the past year, his lab has published two breakthrough papers.
In the first paper (Gershoni et al. 2014) the Mishmar group showed that certain genotype combinations of the mitochondrial and nuclear genome, but not each genome alone, alter the susceptibility to develop type 2 diabetes. Secondly, they showed that certain interacting proteins from the mitochondrial and nuclear genomes mutate in a coordinated way during the evolution of vertebrates. Finally, they showed that disruption of this mito-nuclear genotype combination by introducing mutations from other species into the human proteins interfere with physical interactions of proteins important for the activity of the first and largest protein complex of the mitochondrial energy production system, complex I.
In the second paper (Blumberg et al. 2014) the Mishmar lab were the first to identify c-Jun, Jun-D and CEBPb, bona fide transcriptional regulators of nuclear genes, within human mitochondria and showed that these factors bind the human mitochondrial genome within protein coding genes, rather than in known non-coding regulatory elements. They demonstrated that these binding sites are under Darwinian selection, thus suggesting that mitochondrial DNA sequences have dual roles: the same sequences both code for genes and for regulatory elements.
