title: Mito-nuclear interactions as drivers of gene movement on and off the X-chromosome.
abstract: BACKGROUND
  Mito-nuclear gene interactions regulate energy conversion, and are fundamental to eukaryotes. Generally, mito-nuclear coadaptation would be most efficient if the interacting nuclear genes were X-linked, because this maximizes the probability of favorable mito-nuclear allelic combinations co-transmitting across generations. Thus, under a coadaptation (CA) hypothesis, nuclear genes essential for mitochondrial function might be under selection to relocate to the X-chromosome. However, maternal inheritance predisposes the mitochondrial DNA (mtDNA) to accumulate variation that, while male-harming, is benign to females. Numerous nuclear genes were recently reported in Drosophila melanogaster, which exhibit male-specific patterns of differential expression when placed alongside different mtDNA haplotypes, suggesting that nuclear genes are sensitive to an underlying male-specific mitochondrial mutation load. These genes are thus candidates for involvement in mito-nuclear interactions driven by sexual conflict (SC), and selection might have moved them off the X-chromosome to facilitate an optimal evolutionary counter-response, through males, to the presence of male-harming mtDNA mutations. Furthermore, the presence of male-harming mtDNA mutations could exert selection for modifiers on the Y-chromosome, thus placing these mito-sensitive nuclear genes at the center of an evolutionary tug-of-war between mitochondrion and Y-chromosome.We test these hypotheses by examining the chromosomal distributions of three distinct sets of mitochondrial-interacting nuclear genes in D. melanogaster; the first is a list of genes with mitochondrial annotations by Gene Ontologies, the second is a list comprising the core evolutionary-conserved mitochondrial proteome, and the third is a list of genes involved in male-specific responses to maternally-inherited mitochondrial variation and which might be putative targets of Y-chromosomal regulation.
  
  
  RESULTS
  Genes with mitochondrial annotations and genes representing the mitochondrial proteome do not exhibit statistically-significant biases in chromosomal representation. However, genes exhibiting sex-specific sensitivity to mtDNA are under-represented on the X-chromosome, over-represented among genes known to be sensitive to Y-chromosomal variation, and among genes previously associated with male fitness, but under-represented among genes associated with direct sexual antagonism.
  
  
  CONCLUSIONS
  Our results are consistent with the SC hypothesis, suggesting that mitochondrial mutational pressure selects for gene movement off-the-X, hence enabling mito-nuclear coadaptation to proceed along trajectories that result in optimized fitness in both sexes.
authors.affiliation: School of Biological Sciences, Monash University, Clayton 3800, Australia. Bjorn.Rogell@monash.edu.
authors.forename: Björn
authors.initials: B
authors.lastname: Rogell
authors.forename: Rebecca
authors.initials: R
authors.lastname: Dean
authors.forename: Bernardo
authors.initials: B
authors.lastname: Lemos
authors.forename: Damian K
authors.initials: DK
authors.lastname: Dowling
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics*; D005260:Female; D008297:Male; D008938:Mitosis / Q000235:genetics*; D014960:X Chromosome