The DNA sequences of the 11 linear chromosomes of the ∼2.9 Mbp genome of Encephalitozoon cuniculi, an obligate intracellular parasite of mammals, include ∼2000 putative protein-coding genes. The compactness of this genome is associated with the length reduction of various genes. Essential functions are dependent on a minimal set of genes. Phylogenetic analysis supports the hypotheses that microsporidia are related to fungi and have retained a mitochondrion-derived organelle, the mitosome.