Genetic basis of hybrid sterility between Drosophila pseudoobscura and D. persimilis

Speciation is the underlying process that leads to formation of new species, and therefore is the basis of biodiversity. Genes involved in each stage of speciation, such as those involved in interspecies sterility, remain elusive. Male hybrid sterility and postzygotic isolation between Drosophila pseudoobscura and D. persimilis was examined in this study through backcrossing of female hybrids into each parental line (introgression), selecting for a sterile sperm phenotype, needle-eye sperm. Sperm phenotypes did not separate through backcrossing; instead, males presented with multiple sperm phenotypes. A relationship between the phenotypes observed and the potential genes involved was examined through whole genome sequencing and SNP analysis of the DNA of 20 introgressed male hybrid samples. One finding was SNPs for hybrid sperm sterility were species specific. Also, sperm sterility and heteromorphism appear to be controlled by many loci. Further analysis of SNPs isolated in this study has the strong potential to identify candidates for loci involved in formation of needle-eye sperm, and postzygotic male hybrid sterility in other species

Using genetic buffering relationships identified in fission yeast to reveal susceptibilities in cells lacking hamartin or tuberin function

Tuberous sclerosis complex is an autosomal dominant disorder characterized by benign tumors arising from the abnormal activation of mTOR signaling in cells lacking TSC1 (hamartin) or TSC2 (tuberin) activity. To expand the genetic framework surrounding this group of growth regulators, we utilized the model eukaryote Schizosaccharomyces pombe to uncover and characterize genes that buffer the phenotypic effects of mutations in the orthologous tsc1 or tsc2 loci. Our study identified two genes: fft3 (encoding a DNA helicase) and ypa1 (encoding a peptidyle-prolyl cis/trans isomerase). While the deletion of fft3 or ypa1 has little effect in wild-type fission yeast cells, their loss in tsc1Δ or tsc2Δ backgrounds results in severe growth inhibition. These data suggest that the inhibition of Ypa1p or Fft3p might represent an ‘Achilles’ heel’ of cells defective in hamartin/tuberin function. Furthermore, we demonstrate that the interaction between tsc1/tsc2 and ypa1 can be rescued through treatment with the mTOR inhibitor, torin-1, and that ypa1Δ cells are resistant to the glycolytic inhibitor, 2-deoxyglucose. This identifies ypa1 as a novel upstream regulator of mTOR and suggests that the effects of ypa1 loss, together with mTOR activation, combine to result in a cellular maladaptation in energy metabolism that is profoundly inhibitory to growth