Sequence comparison across multiple organisms aids in the detection of regions under selection. However, resource limitations require a prioritization of genomes to be sequenced. This prioritization should be grounded in two considerations: the lineal scope encompassing the biological phenomena of interest, and the optimal species within that scope for detecting functional elements. We introduce a statistical framework for optimal species subset selection, based on maximizing power to detect conserved sites. Analysis of a phylogenetic star topology shows theoretically that the optimal species subset is not in general the most evolutionarily diverged subset. We then demonstrate this finding empirically in a study of vertebrate species. Our results suggest that marsupials are prime sequencing candidates.