Thymocyte subpopulation enriched for progenitors with an unrearranged T-cell receptor beta-chain gene

The development of T cells within the thymus is not well understood. It is known that thymocytes are derived from a progenitor cell in the bone marrow, the prothymocyte, and that cells in the subcapsular area of the thymus can give rise to progeny in both the cortex and the medulla. However, it is not clear whether all medullary thymocytes are necessarily derived from cortical cells. In particular, it has been difficult to distinguish intrathymic progenitor cells. Recently, however, Lesley et al. have defined a thymocyte subpopulation which can be isolated by treatment of the thymus with cytotoxic anti-Thy-1 antibodies and that seems to be enriched for thymocyte progenitors as measured first by its ability to repopulate transiently the thymus of an irradiated host, and second, by its high content of cells bearing Pgp-1 (refs 10, 11), a cell-surface glycoprotein of relative molecular mass 95,000 that is present on most or all prothymocytes of the bone marrow and on fetal thymocytes, but on only a few per cent of cells in the adult thymus. We show here that the gene encoding the beta-chain of the T-cell receptor for antigen, which is rearranged during T-cell ontogeny, is predominantly in the germline configuration in these cells.     

Pattern of nucleotide substitution at major histocompatibility complex class I loci reveals overdominant selection

The major histocompatibility complex (MHC) loci are known to be highly polymorphic in humans, mice and certain other mammals, with heterozygosity as high as 80-90% (ref. 1). Four different hypotheses have been proposed to explain this high degree of polymorphism: (1) a high mutation rate, (2) gene conversion or interlocus genetic exchange, (3) over dominant selection and (4) frequency-dependent selection. In an attempt to establish which of these hypotheses is correct, we examined the pattern of nucleotide substitution between polymorphic alleles in the region of the antigen recognition site (ARS) and other regions of human and mouse class I MHC genes. The results indicate that in ARS the rate of nonsynonymous (amino acid altering) substitution is significantly higher than that of synonymous substitution in both humans and mice, whereas in other regions the reverse is true. This observation, together with a theoretical study and other considerations, supports the hypothesis of overdominant selection (heterozygote advantage).     

Ant parasite queens revert to mating singly

Multiple mating (polyandry) is widespread among animal groups, particularly insects. But the factors that maintain it and underlie its evolution are hard to verify because benefits and costs are not easily quantified and they tend to be similar in related species. Here we compare the mating strategies of the leaf-cutting ant Acromyrmex echinatior and its recently derived social parasite Acromyrmex insinuator, which is also its closest relative. We find that although the host queens mate with up to a dozen different males, the social parasite mates only singly. This rapid and surprising reversion to single mating in a socially parasitic ant indicates that the costs of polyandry are probably specific to a free-living lifestyle.     

Activation of Escherichia coli prohaemolysin to the mature toxin by acyl carrier protein-dependent fatty acylation

Haemolysin secreted by pathogenic Escherichia coli binds to mammalian cell membranes, disrupting cellular activities and lysing cells by pore-formation. It is synthesized as nontoxic prohaemolysin (proHlyA), which is activated intracellularly by a mechanism dependent on the cosynthesized HlyC. Haemolysin is one of a family of membrane-targeted toxins, including the leukotoxins of Pasteurella and Actinobacillus and the bifunctional adenylate cyclase haemolysin of Bordetella pertussis, which require this protoxin activation 1-5. HlyC alone cannot activate proHlyA, but requires a cytosolic activating factor6. Here we report the cytosolic activating factor is identical to the acyl carrier protein and that activation to mature toxin is achieved by the transfer of a fatty acyl group from acyl carrier protein to proHlyA. Only acyl carrier protein, not acyl-CoA, can promote HlyC-directed proHlyA acylation, but a range of acyl groups are effective.     

Coral reef diversity refutes the neutral theory of biodiversity

The global decline of coral reefs highlights the need to understand the mechanisms that regulate community structure and sustain biodiversity in these systems. The neutral theory, which assumes that individuals are demographically identical regardless of species, seeks to explain ubiquitous features of community structure and biodiversity patterns. Here we present a test of neutral-theory predictions with the use of an extensive species-level data set of Indo-Pacific coral communities. We show that coral assemblages differ markedly from neutral-model predictions for patterns of community similarity and the relative abundance of species. Within local communities, neutral models do not fit relative abundance distributions as well as the classical log-normal distribution. Relative abundances of species across local communities also differ markedly from neutral-theory predictions: coral communities exhibit community similarity values that are far more variable, and lower on average, than the neutral theory can produce. Empirical community similarities deviate from the neutral model in a direction opposite to that predicted in previous critiques of the neutral theory. Instead, our results support spatio-temporal environmental stochasticity as a major driver of diversity patterns on coral reefs.     

Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia

The vanilloid receptor-1 (VR1) is a ligand-gated, non-selective cation channel expressed predominantly by sensory neurons. VR1 responds to noxious stimuli including capsaicin, the pungent component of chilli peppers, heat and extracellular acidification, and it is able to integrate simultaneous exposure to these stimuli. These findings and research linking capsaicin with nociceptive behaviours (that is, responses to painful stimuli in animals have led to VR1 being considered as important for pain sensation. Here we have disrupted the mouse VR1 gene using standard gene targeting techniques. Small diameter dorsal root ganglion neurons isolated from VR1-null mice lacked many of the capsaicin-, acid- and heat-gated responses that have been previously well characterized in small diameter dorsal root ganglion neurons from various species. Furthermore, although the VR1-null mice appeared normal in a wide range of behavioural tests, including responses to acute noxious thermal stimuli, their ability to develop carrageenan-induced thermal hyperalgesia was completely absent. We conclude that VR1 is required for inflammatory sensitization to noxious thermal stimuli but also that alternative mechanisms are sufficient for normal sensation of noxious heat.     

Recombination signal sequences restrict chromosomal V(D)J recombination beyond the 12/23 rule

The genes encoding the variable regions of lymphocyte antigen receptors are assembled from variable (V), diversity (D) and joining (J) gene segments. V(D)J recombination is initiated by the recombinase activating gene (RAG)-1 and -2 proteins, which introduce DNA double-strand breaks between the V, D and J segments and their flanking recombination signal sequences (RSSs). Generally expressed DNA repair proteins then carry out the joining reaction. The conserved heptamer and nonamer sequences of the RSSs are separated by non-conserved spacers of 12 or 23 base pairs (forming 12-RSSs and 23-RSSs). The 12/23 rule, which is mediated at the level of RAG-1/2 recognition and cutting, specifies that V(D)J recombination occurs only between a gene segment flanked by a 12-RSS and one flanked by a 23-RSS. Vbeta segments are appended to DJbeta rearrangements, with little or no direct Vbeta to Jbeta joining, despite 12/23 compatibility of Vbeta 23-RSSs and Jbeta12-RSSs. Here we use embryonic stem cells and mice with a modified T-cell receptor (TCR)beta locus containing only one Dbeta (Dbeta1) gene segment and one Jbeta (Jbeta1) gene cluster to show that the 5' Dbeta1 12-RSS, but not the Jbeta1 12-RSSs, targets rearrangement of a diverse Vbeta repertoire. This targeting is precise and position-independent. This additional restriction on V(D)J recombination has important implications for the regulation of variable region gene assembly and repertoire development.     

A human oncogene formed by the fusion of truncated tropomyosin and protein tyrosine kinase sequences

A biologically active complementary DNA clone of a transforming gene present in a human colon carcinoma contains gene sequences of both tropomyosin and a previously unknown protein tyrosine kinase. The predicted protein (641 amino acids) encoded by this oncogene seems to have been formed by a somatic rearrangement that replaced the extracellular domain of a putative transmembrane receptor by the first 221 amino acids of a non-muscle tropomyosin molecule.     

Export of dissolved organic carbon from peatlands under elevated carbon dioxide levels

Peatlands represent a vast store of global carbon. Observations of rapidly rising dissolved organic carbon concentrations in rivers draining peatlands have created concerns that those stores are beginning to destabilize. Three main factors have been put forward as potential causal mechanisms, but it appears that two alternatives--warming and increased river discharge--cannot offer satisfactory explanations. Here we show that the third proposed mechanism, namely shifting trends in the proportion of annual rainfall arriving in summer, is similarly unable to account for the trend. Instead we infer that a previously unrecognized mechanism--carbon dioxide mediated stimulation of primary productivity--is responsible. Under elevated carbon dioxide levels, the proportion of dissolved organic carbon derived from recently assimilated carbon dioxide was ten times higher than that of the control cases. Concentrations of dissolved organic carbon appear far more sensitive to environmental drivers that affect net primary productivity than those affecting decomposition alone.