The cost of inbreeding in Arabidopsis

Population geneticists have long sought to estimate the distribution of selection intensities among genes of diverse function across the genome. Only recently have DNA sequencing and analytical techniques converged to make this possible. Important advances have come from comparing genetic variation within species (polymorphism) with fixed differences between species (divergence). These approaches have been used to examine individual genes for evidence of selection. Here we use the fact that the time since species divergence allows combination of data across genes. In a comparison of amino-acid replacements among species of the mustard weed Arabidopsis with those among species of the fruitfly Drosophila, we find evidence for predominantly beneficial gene substitutions in Drosophila but predominantly detrimental substitutions in Arabidopsis. We attribute this difference to the Arabidopsis mating system of partial self-fertilization, which corroborates a prediction of population genetics theory that species with a high frequency of inbreeding are less efficient in eliminating deleterious mutations owing to their reduced effective population size.     

Strong male-driven evolution of DNA sequences in humans and apes

Studies of human genetic diseases have suggested a higher mutation rate in males than in females and the male-to-female ratio (alpha) of mutation rate has been estimated from DNA sequence and microsatellite data to be about 4-6 in higher primates. Two recent studies, however, claim that alpha is only about 2 in humans. This is even smaller than the estimates (alpha > 4) for carnivores and birds; humans should have a higher alpha than carnivores and birds because of a longer generation time and a larger sex difference in the number of germ cell cycles. To resolve this issue, we sequenced a noncoding fragment on Y of about 10.4 kilobases (kb) and a homologous region on chromosome 3 in humans, greater apes, and lesser apes. Here we show that our estimate of alpha from the internal branches of the phylogeny is 5.25 (95% confidence interval (CI) 2.44 to infinity), similar to the previous estimates, but significantly higher than the two recent ones. In contrast, for the external (short, species-specific) branches, alpha is only 2.23 (95% CI: 1.47-3.84). We suggest that closely related species are not suitable for estimating alpha, because of ancient polymorphism and other factors. Moreover, we provide an explanation for the small estimate of alpha in a previous study. Our study reinstates a high alpha in hominoids and supports the view that DNA replication errors are the primary source of germline mutation.     

Instant neural control of a movement signal

The activity of motor cortex (MI) neurons conveys movement intent sufficiently well to be used as a control signal to operate artificial devices, but until now this has called for extensive training or has been confined to a limited movement repertoire. Here we show how activity from a few (7-30) MI neurons can be decoded into a signal that a monkey is able to use immediately to move a computer cursor to any new position in its workspace (14 degrees x 14 degrees visual angle). Our results, which are based on recordings made by an electrode array that is suitable for human use, indicate that neurally based control of movement may eventually be feasible in paralysed humans.     

Active fluidization of polymer networks through molecular motors

Entangled polymer solutions and melts exhibit elastic, solid-like resistance to quick deformations and a viscous, fluid-like response to slow deformations. This viscoelastic behaviour reflects the dynamics of individual polymer chains driven by brownian motion: since individual chains can only move in a snake-like fashion through the mesh of surrounding polymer molecules, their diffusive transport, described by reptation, is so slow that the relaxation of suddenly imposed stress is delayed. Entangled polymer solutions and melts therefore elastically resist deforming motions that occur faster than the stress relaxation time. Here we show that the protein myosin II permits active control over the viscoelastic behaviour of actin filament solutions. We find that when each actin filament in a polymerized actin solution interacts with at least one myosin minifilament, the stress relaxation time of the polymer solution is significantly shortened. We attribute this effect to myosin's action as a 'molecular motor', which allows it to interact with randomly oriented actin filaments and push them through the solution, thus enhancing longitudinal filament motion. By superseding reptation with sliding motion, the molecular motors thus overcome a fundamental principle of complex fluids: that only depolymerization makes an entangled, isotropic polymer solution fluid for quick deformations.     

Using the fossil record to estimate the age of the last common ancestor of extant primates

Divergence times estimated from molecular data often considerably predate the earliest known fossil representatives of the groups studied. For the order Primates, molecular data calibrated with various external fossil dates uniformly suggest a mid-Cretaceous divergence from other placental mammals, some 90 million years (Myr) ago, whereas the oldest known fossil primates are from the basal Eocene epoch (54-55 Myr ago). The common ancestor of primates should be earlier than the oldest known fossils, but adequate quantification is needed to interpret possible discrepancies between molecular and palaeontological estimates. Here we present a new statistical method, based on an estimate of species preservation derived from a model of the diversification pattern, that suggests a Cretaceous last common ancestor of primates, approximately 81.5 Myr ago, close to the initial divergence time inferred from molecular data. It also suggests that no more than 7% of all primate species that have ever existed are known from fossils. The approach unites all the available palaeontological methods of timing evolutionary events: the fossil record, extant species and clade diversification models.     

Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2)

Streptomyces coelicolor is a representative of the group of soil-dwelling, filamentous bacteria responsible for producing most natural antibiotics used in human and veterinary medicine. Here we report the 8,667,507 base pair linear chromosome of this organism, containing the largest number of genes so far discovered in a bacterium. The 7,825 predicted genes include more than 20 clusters coding for known or predicted secondary metabolites. The genome contains an unprecedented proportion of regulatory genes, predominantly those likely to be involved in responses to external stimuli and stresses, and many duplicated gene sets that may represent 'tissue-specific' isoforms operating in different phases of colonial development, a unique situation for a bacterium. An ancient synteny was revealed between the central 'core' of the chromosome and the whole chromosome of pathogens Mycobacterium tuberculosis and Corynebacterium diphtheriae. The genome sequence will greatly increase our understanding of microbial life in the soil as well as aiding the generation of new drug candidates by genetic engineering.     

Allometric cascade as a unifying principle of body mass effects on metabolism

The power function of basal metabolic rate scaling is expressed as aM(b), where a corresponds to a scaling constant (intercept), M is body mass, and b is the scaling exponent. The 3/4 power law (the best-fit b value for mammals) was developed from Kleiber's original analysis and, since then, most workers have searched for a single cause to explain the observed allometry. Here we present a multiple-causes model of allometry, where the exponent b is the sum of the influences of multiple contributors to metabolism and control. The relative strength of each contributor, with its own characteristic exponent value, is determined by the control contribution. To illustrate its use, we apply this model to maximum versus basal metabolic rates to explain the differing scaling behaviour of these two biological states in mammals. The main difference in scaling is that, for the basal metabolic rate, the O(2) delivery steps contribute almost nothing to the global b scaling exponent, whereas for the maximum metabolic rate, the O(2) delivery steps significantly increase the global b value.     

Low host specificity of herbivorous insects in a tropical forest

Two decades of research have not established whether tropical insect herbivores are dominated by specialists or generalists. This impedes our understanding of species coexistence in diverse rainforest communities. Host specificity and species richness of tropical insects are also key parameters in mapping global patterns of biodiversity. Here we analyse data for over 900 herbivorous species feeding on 51 plant species in New Guinea and show that most herbivorous species feed on several closely related plant species. Because species-rich genera are dominant in tropical floras, monophagous herbivores are probably rare in tropical forests. Furthermore, even between phylogenetically distant hosts, herbivore communities typically shared a third of their species. These results do not support the classical view that the coexistence of herbivorous species in the tropics is a consequence of finely divided plant resources; non-equilibrium models of tropical diversity should instead be considered. Low host specificity of tropical herbivores reduces global estimates of arthropod diversity from 31 million (ref. 1) to 4 6 million species. This finding agrees with estimates based on taxonomic collections, reconciling an order of magnitude discrepancy between extrapolations of global diversity based on ecological samples of tropical communities with those based on sampling regional faunas.     

Annexin II light chain regulates sensory neuron-specific sodium channel expression

The tetrodotoxin-resistant sodium channel Na(V)1.8/SNS is expressed exclusively in sensory neurons and appears to have an important role in pain pathways. Unlike other sodium channels, Na(V)1.8 is poorly expressed in cell lines even in the presence of accessory beta-subunits. Here we identify annexin II light chain (p11) as a regulatory factor that facilitates the expression of Na(V)1.8. p11 binds directly to the amino terminus of Na(V)1.8 and promotes the translocation of Na(V)1.8 to the plasma membrane, producing functional channels. The endogenous Na(V)1.8 current in sensory neurons is inhibited by antisense downregulation of p11 expression. Because direct association with p11 is required for functional expression of Na(V)1.8, disrupting this interaction may be a useful new approach to downregulating Na(V)1.8 and effecting analgesia.