Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.

Here we report the genome sequence of the honeybee Apis mellifera, a key model for social behaviour and essential to global ecology through pollination. Compared with other sequenced insect genomes, the A. mellifera genome has high A+T and CpG contents, lacks major transposon families, evolves more slowly, and is more similar to vertebrates for circadian rhythm, RNA interference and DNA methylation genes, among others. Furthermore, A. mellifera has fewer genes for innate immunity, detoxification enzymes, cuticle-forming proteins and gustatory receptors, more genes for odorant receptors, and novel genes for nectar and pollen utilization, consistent with its ecology and social organization. Compared to Drosophila, genes in early developmental pathways differ in Apis, whereas similarities exist for functions that differ markedly, such as sex determination, brain function and behaviour. Population genetics suggests a novel African origin for the species A. mellifera and insights into whether Africanized bees spread throughout the New World via hybridization or displacement.

Drosophila melanogaster is a valuable invertebrate model for viral infection and antiviral immunity, and is a focus for studies of insect-virus coevolution. Here we use a metagenomic approach to identify more than 20 previously undetected RNA viruses and a DNA virus associated with wild D. melanogaster. These viruses not only include distant relatives of known insect pathogens but also novel groups of insect-infecting viruses. By sequencing virus-derived small RNAs, we show that the viruses represent active infections of Drosophila. We find that the RNA viruses differ in the number and properties of their small RNAs, and we detect both siRNAs and a novel miRNA from the DNA virus. Analysis of small RNAs also allows us to identify putative viral sequences that lack detectable sequence similarity to known viruses. By surveying >2,000 individually collected wild adult Drosophila we show that more than 30% of D. melanogaster carry a detectable virus, and more than 6% carry multiple viruses. However, despite a high prevalence of the Wolbachia endosymbiont—which is known to be protective against virus infections in Drosophila—we were unable to detect any relationship between the presence of Wolbachia and the presence of any virus. Using publicly available RNA-seq datasets, we show that the community of viruses in Drosophila laboratories is very different from that seen in the wild, but that some of the newly discovered viruses are nevertheless widespread in laboratory lines and are ubiquitous in cell culture. By sequencing viruses from individual wild-collected flies we show that some viruses are shared between D. melanogaster and D. simulans. Our results provide an essential evolutionary and ecological context for host–virus interaction in Drosophila, and the newly reported viral sequences will help develop D. melanogaster further as a model for molecular and evolutionary virus research.

The availability of complete genome sequence from 12 Drosophila species presents the opportunity to examine how natural selection has affected patterns of gene family evolution and sequence divergence among different components of the innate immune system. We have identified orthologs and paralogs of 245 Drosophila melanogaster immune-related genes in these recently sequenced genomes. Genes encoding effector proteins, and to a lesser extent genes encoding recognition proteins, are much more likely to vary in copy number across species than genes encoding signaling proteins. Furthermore, we can trace the apparent recent origination of several evolutionarily novel immune-related genes and gene families. Using codon-based likelihood methods, we show that immune-system genes, and especially those encoding recognition proteins, evolve under positive darwinian selection. Positively selected sites within recognition proteins cluster in domains involved in recognition of microorganisms, suggesting that molecular interactions between hosts and pathogens may drive adaptive evolution in the Drosophila immune system.

Antimicrobial peptides (AMPs) are essential components of immune defenses of multicellular organisms and are currently in development as anti-infective drugs. AMPs have been classically assumed to have broad-spectrum activity and simple kinetics, but recent evidence suggests an unexpected degree of specificity and a high capacity for synergies. Deeper evaluation of the molecular evolution and population genetics of AMP genes reveals more evidence for adaptive maintenance of polymorphism in AMP genes than has previously been appreciated, as well as adaptive loss of AMP activity. AMPs exhibit pharmacodynamic properties that reduce the evolution of resistance in target microbes, and AMPs may synergize with one another and with conventional antibiotics. Both of these properties make AMPs attractive for translational applications. However, if AMPs are to be used clinically, it is crucial to understand their natural biology in order to lessen the risk of collateral harm and avoid the crisis of resistance now facing conventional antibiotics.