The effects of genome size reduction on cellular processes

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The human genome is very large, and our genes contain very long stretches of non-coding sequences called introns. Proper gene expression requires that introns be removed from messenger RNAs prior to their translation into proteins, and this task is carried out by a large, macromolecular, cellular machine called the spliceosome. However, not all genomes are large. As genomes are reduced, non-coding sequences such as introns can be shortened, or lost, and complex cellular machines are reduced in size and have fewer components. I propose to examine the process of splicing in eukaryotes with the smallest nuclear genomes known. Identifying common features of reduced splicing systems in unrelated organisms allows for predicting a functional core of the spliceosome, and identifies other constraints in the system (such as intron sequence features) that might otherwise be obscured in more complex systems. Microsporidia are unicellular, eukaryotic parasites that possess Nature's smallest non-organelle genomes and are my main study group. Although common parasites of animals, genomes are characterized for only a small number of species. In an attempt to increase our understanding of genome diversity within the group, and broaden our understanding of host-parasite relationships, I propose to characterize the infection pattern, and genome and transcript architecture of a new microsporidian parasite of nematodes (microscopic round worms). Understanding organismal diversity is key to comprehending life on this planet, and understanding the underlying diversity at the cellular level is just as crucial. By investigating the flexibility of a key eukaryotic process in a cellular system that is highly reduced, yet still functions, we can gain mechanistic understanding. This research impacts the fields of evolutionary genetics, molecular parasitology, splicing biochemistry and microbial genomics.