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. This thesis
makes three contributions to 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 exciting 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, large-scale
genome rearrangements have the potential to complement sequence-based
methods in the reconstruction of the evolutionary history of
species. Third, we apply comparative genomics methods to study the
global conservation patterns of microRNAs, a recently-discovered class
of small, non-coding RNAs which regulate a large fraction of all genes
in animal and plant genomes. Although the function and conservation of
a few specific microRNAs have been previously studied, this is the first
large-scale, global analysis of microRNA target evolution across the
very large phylogenetic distances separating vertebrates, flies and
nematodes.