Wigglesworthia glossinidia brevipalpis, the obligate bacterial endosymbiont of the tsetse fly Glossina brevipalpis, is characterized by extreme genome reduction and AT nucleotide composition bias. Here, multivariate statistical analyses are used to test the hypothesis that mutational bias and genetic drift shape synonymous codon usage and amino acid usage of Wigglesworthia. The results show that synonymous codon usage patterns vary little across the genome and do not distinguish genes of putative high and low expression levels, thus indicating a lack of translational selection. Extreme AT composition bias across the genome also drives relative amino acid usage, but predicted high-expression genes (ribosomal proteins and chaperonins) use GC-rich amino acids more frequently than do low-expression genes. The levels and configuration of amino acid differences between Wigglesworthia and Escherichia coli were compared to test the hypothesis that the relatively GC-rich amino acid profiles of high-expression genes reflect greater amino acid conservation at these loci. This hypothesis is supported by reduced levels of protein divergence at predicted high-expression Wigglesworthia genes and similar configurations of amino acid changes across expression categories. Combined, the results suggest that codon and amino acid usage in the Wigglesworthia genome reflect a strong AT mutational bias and elevated levels of genetic drift, consistent with expected effects of an endosymbiotic lifestyle and repeated population bottlenecks. However, these impacts of mutation and drift are apparently attenuated by selection on amino acid composition at high-expression genes.