Background

Mitochondria, the power plant of the cell, is the only extra-nuclear organelle harboring its own independent genome, which is strictly maternally inherited in vertebrates. The mitochondrial genome (mtDNA) is 10 times more variable than any coding region in the nuclear genome, a trait that is exploited by molecular evolutionists investigating human genetic history. Nevertheless, some mutations defining human variation occur in highly conserved positions within the 37 genes encoded by the mtDNA. Since mtDNA genes encode key players in the major source for cellular energy - the OXPHOS pathway, genetic variants could affect their activities. This is further complicated by the fact that factors needed for mitochondrial function are encoded by the nuclear and mitochondrial genome, differing 10 times in their mutation rates. How does this the genetic variation affect function? How do mitochondrial and nuclear proteins cooperate?

Current Projects

My group’s projects focus on two aspects of mitochondrial genetics:

(1) Human mitochondrial DNA (mtDNA) variation and the tendency to develop complex disorders, focusing on type II diabetes mellitus (T2DM), diabetic complications and Schizophrenia.

(2) Deciphering the evolutionary and functional advantage in the evolutionary increase of complexity, focusing on the first and largest protein complex of the mitochondrial respiratory chain, NADH Ubiquinone Oxidoreductase (complex I).

Recent Publications

Levin.L & Mishmar.D.(2017).The genomic landscape of evolutionary convergence in mammals, birds and reptiles. Nature Ecology & Evolution,10.1038/s41559-016-0041 Link

Blumberg, A., Kundaje, A., Danko, C. G., & Mishmar, D. (2017). Initiation of mtDNA transcription is followed by pausing, and diverge across human cell types and during evolution. Genome Research, gr-209924.‏ Link

Cohen T, Levin L, Mishmar D (2016) Ancient Out-of-Africa Mitochondrial DNA Variants Associate with Distinct Mitochondrial Gene Expression Patterns. PLoS Genet 12(11): e1006407. doi:10.1371/journal.pgen.1006407 Link

Bar-Yaacov, D., I. Frumkin, Y. Yashiro, T. Chujo, Y. Ishigami, Y. Chemla, A. Blumberg, O. Schlesinger, P. Bieri, B. Greber, N. Ban, R. Zarivach, L. Alfonta, Y. Pilpel, T. Suzuki and D. Mishmar (2016). "Mitochondrial 16S rRNA Is Methylated by tRNA Methyltransferase TRMT61B in All Vertebrates." PLoS Biol 14(9): e1002557. Link

Bar-Yaacov D, Hadjivasiliou Z, Levin L, Barshad G, Zarivach R, Bouskila A, Mishmar D. Mitochondrial involvement in vertebrate speciation? The case of mito-nuclear genetic divergence in chameleons. Genome Biol Evol . 2015 Dec 1;7(12):3322-36.Link

Ph.D. The Hebrew University of Jerusalem, 2000.