Dengue-like viruses isolated by an improved method

Zusammenfassung Aus Seren von Dengue-Fieberkranken (Epidemie 1963) wurden zwei «Dengue-like» Viren isoliert. Die Isolierung der Stämme gelang in Bristol-HeLa-Zellen, die mit dem LKB 6300 A Ultrafilter dargestellt wurden. Die Identifizierung der Viren erfolgte mit der Reaktion der Komplementbindung.     

Genome-scale approaches to resolving incongruence in molecular phylogenies

One of the most pervasive challenges in molecular phylogenetics is the incongruence between phylogenies obtained using different data sets, such as individual genes. To systematically investigate the degree of incongruence, and potential methods for resolving it, we screened the genome sequences of eight yeast species and selected 106 widely distributed orthologous genes for phylogenetic analyses, singly and by concatenation. Our results suggest that data sets consisting of single or a small number of concatenated genes have a significant probability of supporting conflicting topologies. By contrast, analyses of the entire data set of concatenated genes yielded a single, fully resolved species tree with maximum support. Comparable results were obtained with a concatenation of a minimum of 20 genes; substantially more genes than commonly used but a small fraction of any genome. These results have important implications for resolving branches of the tree of life.     

A 3' splice site-binding sequence in the catalytic core of a group I intron

Ribozymes use specific RNA-RNA interactions for substrate binding and active-site formation. Self-splicing group I introns have approximately 70 nucleotides constituting the core, a region containing sequences and structures indispensable for catalytic function. The catalytic core must interact with the substrates used for the two steps of the self-splicing reaction, that is, guanosine, the 5'-splice-site helix (P1) and the 3' splice site. Mutational evidence suggests that core sequences near segment J6/7 that joins the base-paired stems P6 and P7, and the bulged base of P7(5'), participate in binding guanosine substrate, but nothing is known about the interactions between the core, the 5'-splice-site helix and the 3' splice site. On the basis of comparative sequence data, it has been suggested that two specific bases in the catalytic core of group I introns might form a binding sequence for the 3' splice site. Here we present genetic evidence that such a binding site exists in the core of the Tetrahymena large subunit ribosomal RNA intron. We demonstrate that this pairing, termed P9.0, is functionally important in the exon ligation step of self-splicing, but is not itself responsible for 3'-splice-site selection.     

Genes mirror geography within Europe

Understanding the genetic structure of human populations is of fundamental interest to medical, forensic and anthropological sciences. Advances in high-throughput genotyping technology have markedly improved our understanding of global patterns of human genetic variation and suggest the potential to use large samples to uncover variation among closely spaced populations. Here we characterize genetic variation in a sample of 3,000 European individuals genotyped at over half a million variable DNA sites in the human genome. Despite low average levels of genetic differentiation among Europeans, we find a close correspondence between genetic and geographic distances; indeed, a geographical map of Europe arises naturally as an efficient two-dimensional summary of genetic variation in Europeans. The results emphasize that when mapping the genetic basis of a disease phenotype, spurious associations can arise if genetic structure is not properly accounted for. In addition, the results are relevant to the prospects of genetic ancestry testing; an individual's DNA can be used to infer their geographic origin with surprising accuracy-often to within a few hundred kilometres.     

Conformational entropy in molecular recognition by proteins

Molecular recognition by proteins is fundamental to almost every biological process, particularly the protein associations underlying cellular signal transduction. Understanding the basis for protein-protein interactions requires the full characterization of the thermodynamics of their association. Historically it has been virtually impossible to experimentally estimate changes in protein conformational entropy, a potentially important component of the free energy of protein association. However, nuclear magnetic resonance spectroscopy has emerged as a powerful tool for characterizing the dynamics of proteins. Here we employ changes in conformational dynamics as a proxy for corresponding changes in conformational entropy. We find that the change in internal dynamics of the protein calmodulin varies significantly on binding a variety of target domains. Surprisingly, the apparent change in the corresponding conformational entropy is linearly related to the change in the overall binding entropy. This indicates that changes in protein conformational entropy can contribute significantly to the free energy of protein-ligand association.