Effects of Interactions between Mitochondrial Haplotype and Nuclear Genotype on the Reproductive Success of the Fruit Fly Drosophila melanogaster

• Applicant: Dr. Ralph Dobler
• Subject Area: Reproductive Medicine, Urology
• Term: from 2013 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 240828102

I aim to provide the lacking experimental proof of principle that different mt-haplotypes expressed in different (isogenic) nuclear backgrounds lead to combination specific variation in male fertilisation-success and female fecundity. The objective of the here proposed pilot project is to investigate the male and female reproductive success of the fruit fly Drosophila melanogaster and to determine to which degree variations in reproductive success can be explained by interactions between mtDNA and nuclear DNA. Knowledge about the amount of variation caused by the DNA interaction is crucial for the understanding of differences in male and female reproductive success on a genetic level and hence to understand why some individuals have a low (or no) reproductive success. I propose an experimental approach where I establish lines of flies with different mt-haplotypes expressed in corresponding isogenic nuclear background (full-factorial design, see 1.2 for details). These unique combinations of fly lines will allow me to experimentally and statistically separate interaction effects between mtDNA and nuclear DNA from other effects (i.e., mainly the proper effects of the two DNA types themselves) causing differences in male and female reproductive success. Knowledge about the interaction effects between mtDNA and nuclear DNA in D. melanogaster can also shed light on the problem of low fertilisation success or infertility in humans, especially as Drosophila is presently proposed as a model system for complex human traits. Mitochondrial DNA in humans and D. melanogaster code for the same 13 gene products which are all constitutive parts of elements involved in the electron transfer-chain. It is thus conceivable that DNA interactions in D. melanogaster and humans have very similar effects on reproductive success. In addition, the insights on effects of DNA interactions obtained from my pilot project can provide crucial input for the field of mitochondrial gene replacement to cure mitochondrial caused diseases. Replacing deficient mtDNA may apparently cause changes in gene expression and hence lead to unpredictable side effects - a fact currently not considered by medical biologists advancing these therapies. Although applied in D. melanogaster, my study will provide basic knowledge to assess and investigate long term and unintended effects of mitochondrial gene replacement in humans.

• DFG Programme: Research Grants