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.

Temporal division of labor and foraging specialization are key characteristics of honeybee social organization. Worker honeybees (Apis mellifera) initiate foraging for food around their third week of life and often specialize in collecting pollen or nectar before they die. Variation in these fundamental social traits correlates with variation in worker reproductive physiology. However, the genetic and hormonal mechanisms that mediate the control of social organization are not understood and remain a central question in social insect biology. Here we demonstrate that a yolk precursor gene, vitellogenin, affects a complex suite of social traits. Vitellogenin is a major reproductive protein in insects in general and a proposed endocrine factor in honeybees. We show by use of RNA interference (RNAi) that vitellogenin gene activity paces onset of foraging behavior, primes bees for specialized foraging tasks, and influences worker longevity. These findings support the view that the worker specializations that characterize hymenopteran sociality evolved through co-option of reproductive regulatory pathways. Further, they demonstrate for the first time how coordinated control of multiple social life-history traits can originate via the pleiotropic effects of a single gene that affects multiple physiological processes.

Haplodiploid organisms comprise about 20% of animals. Males develop from unfertilized eggs while females are derived from fertilized eggs. The underlying mechanisms of sex determination, however, appear to be diverse and are poorly understood. We have dissected the complementary sex determiner (csd) locus in the honeybee to understand its molecular basis. In this species, csd acts as the primary sex-determining signal with several alleles segregating in populations. Males are hemizygous and females are heterozygous at this locus; nonreproducing diploid males occur when the locus is homozygous. We have characterized csd by positional cloning and repression analysis. csd alleles are highly variable and no transcription differences were found between sexes. These results establish csd as a primary signal that governs sexual development by its allelic composition. Structural similarity of csd with tra genes of Dipteran insects suggests some functional relation of what would otherwise appear to be unrelated sex-determination mechanisms.

The colony-level phenotype of an insect society emerges from interactions between large numbers of individuals that may differ considerably in their morphology, physiology, and behavior. The proximate and ultimate mechanisms that allow this complex integrated system to form are not fully known, and understanding the evolution of social life strategies is a major topic in systems biology. In solitary insects, behavior, sensory tuning, and reproductive physiology are linked. These associations are controlled in part by pleiotropic networks that organize the sequential expression of phases in the reproductive cycle. Here we explore whether similar associations give rise to different behavioral phenotypes in a eusocial worker caste. We document that the pleiotropic genetic network that controls foraging behavior in functionally sterile honey bee workers (Apis mellifera) has a reproductive component. Associations between behavior, physiology, and sensory tuning in workers with different foraging strategies indicate that the underlying genetic architectures were designed to control a reproductive cycle. Genetic circuits that make up the regulatory ''ground plan'' of a reproductive strategy may provide powerful building blocks for social life. We suggest that exploitation of this ground plan plays a fundamental role in the evolution of social insect societies.