Genomic compatibility as the backstop at the species boundary

Species divergence is a central theme in evolutionary biology. Speciation begins as genetic differentiation of populations leading to biological differences that will eventually prevent gene flow from one species to another, thus reinforcing the differentiation process. However, the molecular determinants of species differentiation are presently poorly understood. Our recent analysis of the gene flow between mountain hares and brown hares suggests that mitochondria play an important role in enforcing the species boundary.

Mitochondrial proteins are partly encoded by maternally inherited mitochondrial DNA (mtDNA) and partly by bi-parental nuclear DNA. Backed by earlier studies using artificial mitochondrial transfer between species, we hypothesize that the incompatibility of the two genetic compartments could result in decreased hybrid fitness and constitute an important backstop for the species boundary. In the proposed study, we will test the fitness effects of hybrid mitochondria by transferring mtDNA from one hare species to another, measuring the efficiency of oxidative phosphorylation (OXPHOS), production of free radicals, mitochondrial turnover, changes in the signaling between mitochondria and the nucleus, differences in mtDNA maintenance, and expression as well as competition between different haplotypes of mtDNA within the same cell. Genome-wide analysis of 200 hare DNA samples will enable us to identify nuclear genes, which are under selection in hares with non-species specific mtDNA and are important for the genetic compatibility. The function of these candidate genes will be further validated through genetic engineering of hare cells.

The study is tailored to elucidate the molecular mechanisms of species differentiation, nuclear regulation of OXPHOS function, signaling between the mitochondria and the nucleus, as well as to provide new insight into the variation in pathological mechanisms in human mitochondrial diseases. Due to advancing climate change and its impact on mountain hares, aggravated by hybridization with invasive brown hares, the study also has important applications in conservation biology.

The consortium partners involved in the project, will bring together unique expertise in mitochondrial functions and their molecular regulatory networks, genomics and conservation biology.