Nov. 27, 2016
BGU researchers have shown, for the first time, that the ancient migrations out of Africa that gave rise to all human populations in the world left their signatures as functional regulatory mutations in the maternally inherited mitochondrial genome. That is, whereas for the past 30 years, scientists believed the 37 genes of mitochondrial DNA (mtDNA), out of 25,000 genes in the entire genome, merely recorded changes, BGU researchers have now shown that mtDNA mutations have a regulatory impact on mitochondrial function in a way that quantitatively differs between Africans and non-Africans. 


Mitochondria, ancient bacterial-like organelles, are considered to be the major power plants of our cells. They provide the energy for human beings to think, hear, see and move. Such mitochondrial mutations, which occurred during the course of human evolution over the last ~150,000 years, have altered the genetic material of the mitochondria and shaped their regulatory landscape.

Specifically, using a hypothesis-free approach, Prof. Dan Mishmar and his PhD students Tal Cohen and Liron Levin studied gene expression (RNA-seq) in a large group of individuals (454) and discovered that current-day Africans have a distinct expression pattern of genes encoded by the mitochondrial genome, as compared to non-Africans (mainly Caucasians). Gene expression means transcribing the DNA into RNA, which then instructs the body to produce proteins. Their analysis even went so far as to offer a candidate post-transcriptional mechanism involving mitochondrial-targeted RNA-binding proteins that explains such differences. These findings were just published in  PLoS Genetics.

For more than three decades, genetic variations in the mitochondrial genome were considered non-functional and neutral and were, therefore, supposed to have accumulated over time without exerting any impact. This theory led to the usage of mitochondrial genetic variants merely as markers of ancient migrations. However, this view has to be reevaluated in light of the new findings emerging from Ben-Gurion University. Using tools capable of measuring much more subtle differences in mtDNA, Prof. Mishmar and his students have discovered their active role.  

“Our paper shows strong evidence that mitochondrial DNA genetic variants have a regulatory impact, and hence are functional and not passive. This implies that such variants likely played an active role as humans left Africa to populate the rest of the world,” says Mishmar.

“Since our findings change the view of the role of genetic variation in the mitochondrial genome during human evolution, they are likely to be of particular interest to population geneticists, biochemists, evolutionists, archaeologists, anthropologists and even self-educated genealogists,” he adds.

Prof. Mishmar heads BGU’s Center of Evolutionary Genomics and Medicine, and is a faculty member in the Department of Life Sciences, Faculty of Natural Sciences.

This study was supported by grants from the Israel Science Foundation (ISF), Binational Science Foundation (BSF) and by the US Army Life Sciences Division.