Functional profiling of the Saccharomyces cerevisiae genome

Determining the effect of gene deletion is a fundamental approach to understanding gene function. Conventional genetic screens exhibit biases, and genes contributing to a phenotype are often missed. We systematically constructed a nearly complete collection of gene-deletion mutants (96% of annotated open reading frames, or ORFs) of the yeast Saccharomyces cerevisiae. DNA sequences dubbed 'molecular bar codes' uniquely identify each strain, enabling their growth to be analysed in parallel and the fitness contribution of each gene to be quantitatively assessed by hybridization to high-density oligonucleotide arrays. We show that previously known and new genes are necessary for optimal growth under six well-studied conditions: high salt, sorbitol, galactose, pH 8, minimal medium and nystatin treatment. Less than 7% of genes that exhibit a significant increase in messenger RNA expression are also required for optimal growth in four of the tested conditions. Our results validate the yeast gene-deletion collection as a valuable resource for functional genomics.     

Evolutionary genetics: Ambiguous role of CCR5 in Y. pestis infection

Mecsas and colleagues suggest that a deficiency in the chemokine receptor CCR5 in humans is unlikely to confer protection against plague, based on their study of Yersinia pestis infection in Ccr5-deficient mice. They were testing the hypothesis that a mutation in the CCR5 gene, frequently found in Caucasians, may have been selected for in the past because it provided protection against (bubonic) plague; the mutation, called CCR5Delta32, is characterized by a 32-base-pair deletion. We have also tested this hypothesis by using Y. pestis infection in mice and, in addition, we have done phagocytosis experiments with macrophages from wild-type and Ccr5-deficient mice. Although, like Mecsas et al., we did not see any difference in the survival of the two groups of mice, we did find that there was a significantly reduced uptake of Y. pestis by Ccr5-deficient macrophages in vitro. Our results indicate that the role of Ccr5 in Y. pestis infection may therefore be more complex than previously thought.     

Field evidence for surface-wave-induced instability of sand dunes

Field studies of barchans--crescent-shaped dunes that propagate over solid ground under conditions of unidirectional wind--have long focused on the investigation of an equilibrium between sand transport by wind and the control of air flow by dune topography, which are thought to control dune morphology and kinematics. Because of the long timescale involved, however, the underlying dynamic processes responsible for the evolution of dune fields remain poorly understood. Here we combine data from a three-year field study in the Moroccan Sahara with a model study to show that barchans are fundamentally unstable and do not necessarily behave like stable solitary waves, as suggested previously. We find that dune collisions and changes in wind direction destabilize the dunes and generate surface waves on the barchans. Because the resulting surface waves propagate at a higher speed than the dunes themselves, they can produce a series of new barchans of elementary size by breaking the horns of large dunes. The creation of these new dunes provides a mechanism for sand loss that prevents dune fields from merging into a single giant dune and therefore plays a fundamental role in the control of size selection and the development of dune patterns.     

Insect behaviour: arboreal ants build traps to capture prey

To meet their need for nitrogen in the restricted foraging environment provided by their host plants, some arboreal ants deploy group ambush tactics in order to capture flying and jumping prey that might otherwise escape. Here we show that the ant Allomerus decemarticulatus uses hair from the host plant's stem, which it cuts and binds together with a purpose-grown fungal mycelium, to build a spongy 'galleried' platform for trapping much larger insects. Ants beneath the platform reach through the holes and immobilize the prey, which is then stretched, transported and carved up by a swarm of nestmates. To our knowledge, the collective creation of a trap as a predatory strategy has not been described before in ants.     

Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism

Many studies have supported a genetic etiology for autism. Here we report mutations in two X-linked genes encoding neuroligins NLGN3 and NLGN4 in siblings with autism-spectrum disorders. These mutations affect cell-adhesion molecules localized at the synapse and suggest that a defect of synaptogenesis may predispose to autism.     

Truncated TrkB-T1 mediates neurotrophin-evoked calcium signalling in glia cells

The neurotrophin receptor TrkB is essential for normal function of the mammalian brain. It is expressed in three splice variants. Full-length receptors (TrkB(FL)) possess an intracellular tyrosine kinase domain and are considered as those TrkB receptors that mediate the crucial effects of brain-derived neurotrophic factor (BDNF) or neurotrophin 4/5 (NT-4/5). By contrast, truncated receptors (TrkB-T1 and TrkB-T2) lack tyrosine kinase activity and have not been reported to elicit rapid intracellular signalling. Here we show that astrocytes predominately express TrkB-T1 and respond to brief application of BDNF by releasing calcium from intracellular stores. The calcium transients are insensitive to the tyrosine kinase blocker K-252a and persist in mutant mice lacking TrkB(FL). By contrast, neurons produce rapid BDNF-evoked signals through TrkB(FL) and the Na(v)1.9 channel. Expression of antisense TrkB messenger RNA strongly reduces BDNF-evoked calcium signals in glia. Thus, our results show that, unexpectedly, TrkB-T1 has a direct signalling role in mediating inositol-1,4,5-trisphosphate-dependent calcium release; in addition, they identify a previously unknown mechanism of neurotrophin action in the brain.