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This issue includes a landmark collection of papers on the stalwart of the genetics lab, the Drosophila fruit fly. The centrepiece is the publication by the Drosophila 12 Genomes Consortium of the genomic sequence for ten Drosophila species. The paper compares the newly sequenced genomes (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi species), with the two previously known sequences for D. melanogaster and D. pseudoobscura. The resulting database of genetic variation will be invaluable for the study of the forces of evolutionary change. A second major collaboration has mined the dozen Drosophila genome sequences for conserved elements, and reports the relationship between conservation and function for many specific sequence motifs. A detailed regulatory network emerges, identifying protein-coding genes and exons, RNA genes, microRNAs and their targets. These papers are discussed in News and Views. Two further research papers use the new genomic data to study gene expression, first for genes with male-biased expression and those unique to each species and second, to track the evolution of gene dosage compensation on Drosophila sex chromosomes. Four new reviews focus on how the latest work on Drosophila is taking this genetically pliant lab model into exciting new fields. Pierre Leopold and Norbert Perrimon review advances in the study of endocrinology and homeostasis that are establishing Drosophila as a model for mammalian physiology. Drosophila has proved a powerful system in which to study the pathways controlling cell shape in growing tissue, as reported by Thomas Lecuit and Loic Le Goff. Leslie Vosshall reviews the remarkable work linking neural circuits and behaviour and John Lis reviews work on Drosophila that has rewritten the textbook view of gene transcription. The cover shows anaesthetized individuals of all twelve Drosophila species. The evolution of dosage compensation on Drosophila sex chromosomes is examined by using microarrays to determine relative gene expression of sex-linked genes in a number of fly species. How this expression changes over time is discussed, particularly in species with a neo-X chromosome, to determine why genes might have male-biased expression. X chromosomes evolve differently from autosomes, but general governing principles have not emerged1. For example, genes with male-biased expression are under-represented on the X chromosome of D. melanogaster2, but are randomly distributed in the genome of Anopheles gambiae3. In direct global profiling experiments using species-specific microarrays, we find a nearly identical paucity of genes with male-biased expression on D. melanogaster, D. simulans, D. yakuba, D. ananassae, D. virilis and D. mojavensis X chromosomes. We observe the same under-representation on the neo-X of D. pseudoobscura. It has been suggested that precocious meiotic silencing of the X chromosome accounts for reduced X chromosome male-biased expression in nematodes4, mammals5 and Drosophila6. We show that X chromosome genes with male-biased expression are under-represented in somatic cells and in mitotic male germ cells. These data are incompatible with simple X chromosome inactivation models. Using expression profiling and comparative sequence analysis, we show that selective gene extinction on the X chromosome, creation of new genes on autosomes and changed genomic location of existing genes contribute to the unusual X chromosome gene content.

Both genome content and deployment contribute to phenotypic differences between species1-5. Sex is the most important difference between individuals in a species and has long been posited to be rapidly evolving. Indeed, in the Drosophila genus, traits such as sperm length, genitalia, and gonad size are the most obvious differences between species6. Comparative analysis of sex-biased expression should deepen our understanding of the relationship between genome content and deployment during evolution. Using existing7,8 and newly assembled genomes9, we designed species-specific microarrays to examine sex-biased expression of orthologues and species-restricted genes in D. melanogaster, D. simulans, D. yakuba, D. ananassae, D. pseudoobscura, D. virilis and D. mojavensis. We show that averaged sex-biased expression changes accumulate monotonically over time within the genus. However, different genes contribute to expression variance within species groups compared to between groups. We observed greater turnover of species-restricted genes with male-biased expression, indicating that gene formation and extinction may play a significant part in species differences. Genes with male-biased expression also show the greatest expression and DNA sequence divergence. This higher divergence and turnover of genes with male-biased expression may be due to high transcription rates in the male germline, greater functional pleiotropy of genes expressed in females, and/or sexual competition.

Females and males often exhibit conspicuous morphological, physiological and behavioral differences. Similarly, gene expression profiles indicate that a large portion of the genome is sex-differentially deployed, particularly in the germ line. Because males and females are so fundamentally different, each sex is likely to have a different optimal gene expression profile that is never fully achieved in either sex because of antagonistic selection in females versus males. Males are hemizygous for the X chromosome, which means that recessive male-favorable de novo mutations on the X chromosome are subject to immediate selection. In females, a recessive female-favorable mutation on one of two X chromosomes is not available for selection until it becomes frequent enough in the local population to result in homozygous individuals. Given that most mutations are recessive, one would expect that genes or alleles favoring males should accumulate on the X chromosome. Recent microarray work in Drosophila and C. elegans clearly shows the opposite. Why is the X chromosome a highly disfavored location for genes with male-biased expression in these animals? BioEssays 26:543–548, 2004. Published 2004 Wiley Periodicals, Inc.

Sex chromosomes are primary determinants of sexual dimorphism in many organisms. These chromosomes are thought to arise via the divergence of an ancestral autosome pair and are almost certainly influenced by differing selection in males and females. Exploring how sex chromosomes differ from autosomes is highly amenable to genomic analysis. We examined global gene expression in Drosophila melanogaster and report a dramatic underrepresentation of X-chromosome genes showing high relative expression in males. Using comparative genomics, we find that these same X-chromosome genes are exceptionally poorly conserved in the mosquito Anopheles gambiae. These data indicate that the X chromosome is a disfavored location for genes selectively expressed in males.

A global analysis of sex-biased transcription in Drosophila shows extensive differential expression between the sexes. Most sex-differential expression is due to germ cells and nearly all genes with germline expression show sex-bias., Background Sexual dimorphism results in the formation of two types of individuals with specialized reproductive roles and is most evident in the germ cells and gonads. Results We have undertaken a global analysis of transcription between the sexes using a 31,464 element FlyGEM microarray to determine what fraction of the genome shows sex-biased expression, what tissues express these genes, the predicted functions of these genes, and where these genes map onto the genome. Females and males (both with and without gonads), dissected testis and ovary, females and males with genetically ablated germlines, and sex-transformed flies were sampled. Conclusions Using any of a number of criteria, we find extensive sex-biased expression in adults. The majority of cases of sex differential gene expression are attributable to the germ cells. There is also a large class of genes with soma-biased expression. There is little germline-biased expression indicating that nearly all genes with germline expression also show sex-bias. Monte Carlo simulations show that some genes with sex-biased expression are non-randomly distributed in the genome.

Background Drosophila females commit tremendous resources to egg production and males produce some of the longest sperm in the animal kingdom. We know little about the coordinated regulation of gene expression patterns in distant somatic tissues that support the developmental cost of gamete production. Results We determined the non-gonadal gene expression patterns of Drosophila females and males with or without a germline. Our results show that germline-dependent expression in the non-gonadal soma is extensive. Interestingly, gene expression patterns and hormone titers are consistent with a hormone axis between the gonads and non-gonadal soma. Conclusions The germline has a long-range influence on gene expression in the Drosophila sexes. We suggest that this is the result of a germline/soma hormonal axis.

Recent studies have shed new light on translational repression by Nanos and Pumilio proteins. The ancestral function of this repression mechanism appears to be in early germline development; later, species-specific applications in embryonic patterning and spermatogenesis—oogenesis switching evolved.