An empirical test of the mutational landscape model of adaptation using a single-stranded DNA virus

The primary impediment to formulating a general theory for adaptive evolution has been the unknown distribution of fitness effects for new beneficial mutations. By applying extreme value theory, Gillespie circumvented this issue in his mutational landscape model for the adaptation of DNA sequences, and Orr recently extended Gillespie's model, generating testable predictions regarding the course of adaptive evolution. Here we provide the first empirical examination of this model, using a single-stranded DNA bacteriophage related to phiX174, and find that our data are consistent with Orr's predictions, provided that the model is adjusted to incorporate mutation bias. Orr's work suggests that there may be generalities in adaptive molecular evolution that transcend the biological details of a system, but we show that for the model to be useful as a predictive or inferential tool, some adjustments for the biology of the system will be necessary.     

An integrated view of the chemistry and mineralogy of martian soils

The mineralogical and elemental compositions of the martian soil are indicators of chemical and physical weathering processes. Using data from the Mars Exploration Rovers, we show that bright dust deposits on opposite sides of the planet are part of a global unit and not dominated by the composition of local rocks. Dark soil deposits at both sites have similar basaltic mineralogies, and could reflect either a global component or the general similarity in the compositions of the rocks from which they were derived. Increased levels of bromine are consistent with mobilization of soluble salts by thin films of liquid water, but the presence of olivine in analysed soil samples indicates that the extent of aqueous alteration of soils has been limited. Nickel abundances are enhanced at the immediate surface and indicate that the upper few millimetres of soil could contain up to one per cent meteoritic material.     

The Molecule Pages database

The Alliance for Cellular Signaling (AfCS)-Nature Molecule Pages will be a comprehensive database of key facts about more than 3,000 proteins involved in cell signalling. Each entry will be created by invited experts and be peer-reviewed. Alongside the large-scale experiments being conducted by the AfCS scientists, the wealth of information contained in this database offers the potential of accelerating the pace of discovery in signal transduction research.     

Gene silencing: trans-histone regulatory pathway in chromatin

The fundamental unit of eukaryotic chromatin, the nucleosome, consists of genomic DNA wrapped around the conserved histone proteins H3, H2B, H2A and H4, all of which are variously modified at their amino- and carboxy-terminal tails to influence the dynamics of chromatin structure and function -- for example, conjugation of histone H2B with ubiquitin controls the outcome of methylation at a specific lysine residue (Lys 4) on histone H3, which regulates gene silencing in the yeast Saccharomyces cerevisiae. Here we show that ubiquitination of H2B is also necessary for the methylation of Lys 79 in H3, the only modification known to occur away from the histone tails, but that not all methylated lysines in H3 are regulated by this 'trans-histone' pathway because the methylation of Lys 36 in H3 is unaffected. Given that gene silencing is regulated by the methylation of Lys 4 and Lys 79 in histone H3, we suggest that H2B ubiquitination acts as a master switch that controls the site-selective histone methylation patterns responsible for this silencing.     

Malaria in 2002

The burden of malaria is increasing, especially in sub-Saharan Africa, because of drug and insecticide resistance and social and environmental changes. Thus, there is an urgent need for vaccines, new drugs and insecticides. Parasite, mosquito and human genome projects are helping in the search for new control tools and international donors are developing new funding mechanisms that could make them available to poor countries. But these new tools will achieve their maximum impact only if additional resources are deployed to strengthen malaria research and control communities in countries where the new tools will be used.     

Functional neurogenesis in the adult hippocampus

There is extensive evidence indicating that new neurons are generated in the dentate gyrus of the adult mammalian hippocampus, a region of the brain that is important for learning and memory. However, it is not known whether these new neurons become functional, as the methods used to study adult neurogenesis are limited to fixed tissue. We use here a retroviral vector expressing green fluorescent protein that only labels dividing cells, and that can be visualized in live hippocampal slices. We report that newly generated cells in the adult mouse hippocampus have neuronal morphology and can display passive membrane properties, action potentials and functional synaptic inputs similar to those found in mature dentate granule cells. Our findings demonstrate that newly generated cells mature into functional neurons in the adult mammalian brain.     

Crystal structure and mechanism of a calcium-gated potassium channel

Ion channels exhibit two essential biophysical properties; that is, selective ion conduction, and the ability to gate-open in response to an appropriate stimulus. Two general categories of ion channel gating are defined by the initiating stimulus: ligand binding (neurotransmitter- or second-messenger-gated channels) or membrane voltage (voltage-gated channels). Here we present the structural basis of ligand gating in a K(+) channel that opens in response to intracellular Ca(2+). We have cloned, expressed, analysed electrical properties, and determined the crystal structure of a K(+) channel (MthK) from Methanobacterium thermoautotrophicum in the Ca(2+)-bound, opened state. Eight RCK domains (regulators of K(+) conductance) form a gating ring at the intracellular membrane surface. The gating ring uses the free energy of Ca(2+) binding in a simple manner to perform mechanical work to open the pore.