Project Summary Sexual reproduction evolved more than one billion years ago, shortly after the appearance of eukaryotes. Sex is theorized to be an important aspect of creating genetic variation, adapting to new environments, and in removing disadvantageous traits from the gene pool. Despite this, many eukaryotes have reverted to asexual reproductive strategies. Importantly, such transitions to asexual reproduction have huge evolutionary impacts: we see regular examples of this in the rapid spread of invasive, pathogenic, and drug-resistant organisms. Unfortunately, such transitions are notoriously difficult to mechanistically interrogate due to their lack of experimental tractability and the fact that many reversions to asexuality are quite ancient. However, arthropods are rich in recently acquired vertically inherited microbes (e.g., Wolbachia, Rickettsia, and Cardinium) that convert their arthropod hosts to asexual reproduction. So-called “parthenogenesis induction” has been reinvented multiple times across these bacteria and relies on microbial mechanisms for impacting host meiosis or mitosis to alter ploidy. We can manipulate these recently asexual lineages in the lab to mechanistically define the cell biology of asexual reproduction. Furthermore, because there are numerous independent transitions to microbe-mediated asexuality, and lineages will slowly undergo a loss of sexual function, we can use this system to track the genomic and mechanistic consequences of lost sex. The long-term goal of my lab is to link mechanistic processes of mitosis, meiosis, and reproduction to long-term organismal and genomic consequences. This proposal describes my lab’s research goals across the next five years, which include: (1) mechanistically characterizing bacterial proteins mediating asexual reproduction, (2) identifying mitotic- and meiotic- effector proteins across diverse bacteria and reproductive biologies, and (3) using forward genetics to map the genomic consequences of lost sex. Specifically, our creative interdisciplinary research plan integrates genomic approaches (e.g., genome sequencing, comparative genomics, quantitative trait loci mapping), molecular approaches in non-model organisms, and genetics in tractable model systems (e.g., yeast, Drosophila). We will build on our recent discovery of the first putative asexuality inducing bacterial effector proteins to broadly define how microbes have evolved to manipulate mitosis and meiosis, and disentangle the causes of reproductive switches from the consequences. In addition to the broad significance of reproduction, these systems afford new opportunities to understand fundamental aspects of cell biology that underly many human-health relevant processes. For example, defects in mitosis are typical of certain degenerative conditions and cancers, and changes in ploidy significantly contribute to fungal pathogenesis and drug resistance. Our focus on novel mechanisms for altering reproduction and cell ...