Three variations on the theme of comparative genomics: Metagenomics, mitochondrial gene rearrangements and microRNAs

With the emergence of large-scale whole-genome shotgun sequencing in the last decade, comparative genomics has come to the forefront as a fundamental paradigm within the field of bioinformatics. We use the term genomics to refer to the study of all the DNA sequence of an organism in its entirety, and the term comparative genomics to refer to the use of mathematical, computational and statistical tools to compare genomic sequence from several different organisms. Such comparisons have proven to be very successful both for identifying functional genomic elements, such as genes and regulatory elements, as well as for elucidating the evolutionary history of genomes and species.; This thesis makes three different contributions to the field of comparative genomics. First, we extend the comparative method from the comparison of single genomes to the comparison of whole communities of microbial genomes. This is an important problem in the new field of metagenomics, the culture-independent study of entire communities of microbes using the techniques of modern genomic analysis. Second, we study large-scale genome rearrangements (e.g. inversions, transpositions, duplications, etc.) in animal mitochondrial genomes. Aside from being fascinating evolutionary and genetic processes in their own right, the study of large-scale genome rearrangements complements sequence-based methods in the reconstruction of the evolutionary history of species. Finally, we apply classic comparative genomics methods to study the global evolutionary patterns of microRNA networks in vertebrates, flies and nematode worms. MicroRNA s are a recently discovered class of genes which are known to regulate a significant fraction of the genes in animals, plants and their viruses. Although the function and conservation of a few specific microRNAs have been previously studied, this is the first large-scale, global analysis of microRNA network evolution across very large phylogenetic distances in animals.