Cohen 2015 Abstract MiP2015
|Ancient out of Africa mitochondrial DNA variants associate with distinct mitochondrial gene expression patterns.|
Mitochondrial DNA (mtDNA) variants have been used as markers for ancient population migrations. The past decade revealed association of a subset of these variants with altered susceptibility to various disorders, suggesting their functional importance. However, only little is known about the direct genotype-phenotype relationship of ancient mtDNA variants, especially in terms of transcript regulation. Here, by analyzing RNA-seq data from 454 lymphoblast cell lines from unrelated individuals representing major global populations, we show that the variants defining the ancient African genetic background L haplogroup have distinct expression pattern from the rest of the world. This correlation was independent of mtDNA copy number, suggesting that the effect is due to transcript level regulation and not due to variation in mitochondrial quantities. As mtDNA transcription and post-transcription are regulated by nuclear DNA (nDNA) genes we sought for nDNA genes whose expression pattern associated with the L haplogroup. Strikingly, this analysis revealed the best correlation with RNA-binding proteins, of which some are known mitochondrial proteins, thus suggesting post transcriptional candidates to modulate this phenomenon. Our results underline marked change in the regulation of mtDNA transcripts as humans left Africa to populate the rest of the world.
Labels: MiParea: mtDNA;mt-genetics, nDNA;cell genetics, Comparative MiP;environmental MiP
Event: C1, Oral MiP2015
Dept Life Sc, Ben-Gurion Univ Negev, Beer Sheva, Israel. - [email protected]