Grant: Discovery Grants Program - Individual

Life science research is in the midst of a revolution built upon our understanding of DNA, the heredity material of life. Using the tools of modern molecular biology, it is possible to explore the living world in ways unimaginable 20 years ago. One area in which considerable advances have occurred is our understanding of the microbial biosphere. The genomes of thousands of species have been decoded, not only microbes cultured in the lab but those taken directly from their natural habitats: everything from ocean and soil samples to the human gut. Comparative analyses of these genome sequences have shown that lateral gene transfer (LGT)-the exchange of DNA across species bounds-is a major force in the evolution of prokaryotic cells. LGT is now widely accepted as an important mechanism by which bacteria develop resistance to antibiotics, acquire pathogenicity determinants, and adapt to new environments. Much less is known about the extent to which eukaryotic (nucleus-containing) cells engage in LGT. Between-species LGT has been invoked to explain the presence of `unexpected' genes in the genomes of some microbial eukaryotes, as well as those of plants, fungi and even animals. However, the underlying biological mechanisms of such gene transfer events are for the most part unclear. The long-term goal of our research is to elucidate the forces driving genome evolution in eukaryotes. Here we will work towards this goal by focusing on three inter-related short-term objectives: (1) We will generate large, robust genome sequence datasets from within species clusters of single-celled algae and amoebae. (2) We will compare genomes within and between species clusters in order to infer patterns of gene gain and loss over short evolutionary timescales; phylogenetic analyses of patchily distributed genes will allow us to determine the donors of foreign genetic material to these genomes. In particular, we will search for evidence that viruses can act of mediators of LGT in eukaryotes, as they do in prokaryotes. (3) We will compare the DNA sequences of putative LGT-derived genes between closely related strains of our algae and amoebae to look for evidence of natural selection, thereby explicitly testing the hypothesis that prokaryote-to-eukaryote and eukaryote-to-eukaryote LGTs can be adaptive for the recipient organisms. When microbes are considered, Darwin's `tree of life' has begun to look more like a web of life-genes have flowed both vertically and horizontally between diverse life forms for more than three billion years of life on our planet. The data generated in this project will help elucidate the tempo and modes of LGT across the eukaryotic tree, thereby contributing to a robust picture of how microbes adapt and diversify in nature.