Comparison of the gene-expression profiles between adults of Drosophila melanogaster and Drosophila simulans has uncovered the evolution of genes that exhibit sex-dependent regulation. Approximately half the genes showed differences in expression between the species, and among these, approximately 83% involved a gain, loss, increase, decrease, or reversal of sex-biased expression. Most of the interspecific differences in messenger RNA abundance affect male-biased genes. Genes that differ in expression between the species showed functional clustering only if they were sex-biased. Our results suggest that sex-dependent selection may drive changes in expression of many of the most rapidly evolving genes in the Drosophila transcriptome.

Mitochondrial transcription, translation, and respiration require interactions between genes encoded in two distinct genomes, generating the potential for mutations in nuclear and mitochondrial genomes to interact epistatically and cause incompatibilities that decrease fitness. Mitochondrial-nuclear epistasis for fitness has been documented within and between populations and species of diverse taxa, but rarely has the genetic or mechanistic basis of these mitochondrial–nuclear interactions been elucidated, limiting our understanding of which genes harbor variants causing mitochondrial–nuclear disruption and of the pathways and processes that are impacted by mitochondrial–nuclear coevolution. Here we identify an amino acid polymorphism in the Drosophila melanogaster nuclear-encoded mitochondrial tyrosyl–tRNA synthetase that interacts epistatically with a polymorphism in the D. simulans mitochondrial-encoded tRNATyr to significantly delay development, compromise bristle formation, and decrease fecundity. The incompatible genotype specifically decreases the activities of oxidative phosphorylation complexes I, III, and IV that contain mitochondrial-encoded subunits. Combined with the identity of the interacting alleles, this pattern indicates that mitochondrial protein translation is affected by this interaction. Our findings suggest that interactions between mitochondrial tRNAs and their nuclear-encoded tRNA synthetases may be targets of compensatory molecular evolution. Human mitochondrial diseases are often genetically complex and variable in penetrance, and the mitochondrial–nuclear interaction we document provides a plausible mechanism to explain this complexity.

A number of genes associated with sexual traits and reproduction evolve at the sequence level faster than the majority of genes coding for non-sex-related traits. Whole genome analyses allow this observation to be extended beyond the limited set of genes that have been studied thus far. We use cDNA microarrays to demonstrate that this pattern holds in Drosophila for the phenotype of gene expression as well, but in one sex only. Genes that are male-biased in their expression show more variation in relative expression levels between conspecific populations and two closely related species than do female-biased genes or genes with sexually monomorphic expression patterns. Additionally, elevated ratios of interspecific expression divergence to intraspecific expression variation among male-biased genes suggest that differences in rates of evolution may be due in part to natural selection. This finding has implications for our understanding of the importance of sexual dimorphism for speciation and rates of phenotypic evolution.A nisogamous reproduction is common in many animal and plant species and can produce a number of conflicts with important evolutionary consequences. For example, differential selection coefficients between the two sexes can lead to stable genetic polymorphisms or a decline in population mean fitness (1). It can also drive accelerated rates of phenotypic evolution, as many morphologies associated with sex and reproduction diverge more rapidly than other phenotypes (2). Molecular techniques that provide rapid and quantitative measures of genotypic and phenotypic variation have extended this pattern to include accelerated rates of evolution among proteins with sexual or reproductive functions (3, 4). Since then, most data supporting this observation have come from homologous nucleotide sequences of genes that are associated with sex or reproduction. In ciliates, green algae, diatoms, angiosperms, fungi, and at least four animal phyla, unusually high ratios of nonsynonymous to synonymous substitutions (d N ͞d S ) between species have been documented in sex-related genes (reviewed in ref. 5). Some of these genes also show high levels of intraspecific differentiation (5). In Drosophila, much of this work has focused on genes that are expressed in testes or accessory glands (e.g., refs. 6 and 7), although a high d N ͞d S has also been observed for genes expressed in females and components of the sex determination pathway (8).Protein coding sequences provide a natural context for studying rates of evolution, as the effect of a given nucleotide substitution on the polypeptide is predictable, and comparison between neighboring synonymous and nonsynonymous sites controls for mutation rate. Because of the lack of an analogous context for regulatory sequences, the rates and patterns of evolution in regions of the genome controlling gene expression are less well understood. Thus, it is not known whether the rapid rates of evolution among genes associated with sex and reproduction holds for gene expression as w...