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1161. Comparative methods for explaining adaptations.
The ways that taxonomic differences in morphology, behaviour or life history are related to each other and to differences in lifestyle have been used regularly to test ideas about the selective forces involved in their evolution. Such comparative tests have been transformed recently by using increased statistical rigour. The realization that the statistical model against which comparisons are made is a model of how evolution proceeds, forms the basis of a new generation of comparative tests that are grounded properly on phylogenetic reconstruction.
1162. The p53 tumour suppressor gene.
The cell cycle is composed of a series of steps which can be negatively or positively regulated by various factors. Chief among the negative regulators is the p53 protein. Alteration or inactivation of p53 by mutation, or by its interactions with oncogene products of DNA tumour viruses, can lead to cancer. These mutations seem to be the most common genetic change in human cancers.
1164. Structures in colloidal physical chemistry.
The vast range of technological and industrial application of colloidal systems is largely a direct result of their diversity of structure on microscopic and mesoscopic scales. Recent progress in understanding these structures allows for greater control of the macroscopic properties, as well as providing new avenues of fundamental research in physics, chemistry and materials science.
1165. Structure and function of telomeres.
The DNA of telomeres--the terminal DNA-protein complexes of chromosomes--differs notably from other DNA sequences in both structure and function. Recent work has highlighted its remarkable mode of synthesis by the ribonucleoprotein reverse transcriptase, telomerase, as well as its ability to form unusual structures in vitro. Moreover, telomere synthesis by telomerase has been shown to be essential for telomere maintenance and long-term viability.
1166. Enzyme catalysis: not different, just better.
Where are we in our understanding of enzyme catalysis? The gloomier view is that protein structure and enzyme function are the finely balanced end-products of many weak interactions that can be summed only by massive computing power, and more precise parameterization than we enjoy at present. The cheerier position is that proteins are built on definable principles, and that enzymes use recognizable catalytic devices that will allow us to understand how existing enzymes work and to design new ones. To assess which interpretation is the more realistic, the simple reaction catalysed by triosephosphate isomerase is considered here. This examination illustrates some of the catalytic features of enzymes that are understood, and exposes a few that are not. But overall, the question turns out to have an optimistic answer.
1167. The conformation of membranes.
Membranes composed of amphiphilic molecules are highly flexible surfaces that determine the architecture of biological systems and provide a basic structural element for complex fluids such as microemulsions. Physical theories have been developed to describe many aspects of their conformational behaviour, such as the preferred shapes and shape transformations of closed vesicles, and the shape fluctuations, random-surface configurations, and adhesion and unbinding of interacting membranes. Understanding of these phenomena has been much improved through fruitful interactions between theory and experiment.
1168. Man-made antibodies.
Monoclonal antibodies can now be genetically engineered and endowed with new properties. In the future, gene technology could enable antigen-binding fragments to be made by exploiting repertoires of variable domain genes derived from immunized animals and expressed in bacteria. How readily can this approach be extended to production of 'in vitro' repertoires of variable domain genes, and obviate the immunization of animals?
1169. Mitochondrial proteins essential for viability mediate protein import into yeast mitochondria.
Only five mitochondrial proteins are known to be essential for viability of the yeast Saccharomyces cerevisiae; all of them are key components of the mitochondrial protein import system. Other components of this system are not essential for life; they include functionally redundant import receptors on the mitochondrial surface and enzymes acting upon only a few precursor proteins.
1170. The GTPase superfamily: conserved structure and molecular mechanism.
GTPases are conserved molecular switches, built according to a common structural design. Rapidly accruing knowledge of individual GTPases--crystal structures, biochemical properties, or results of molecular genetic experiments--support and generate hypotheses relating structure to function in other members of the diverse family of GTPases.
1171. The GTPase superfamily: a conserved switch for diverse cell functions.
Proteins that bind and hydrolyse GTP are being discovered at a rapidly increasing rate. Each of these many GTPases acts as a molecular switch whose 'on' and 'off' states are triggered by binding and hydrolysis of GTP. Conserved structure and mechanism in myriad versions of the switch--in bacteria, yeast, flies and vertebrates--suggest that all derive from a single primordial protein, repeatedly modified in the course of evolution to perform a dazzling variety of functions.
1172. Molecular dynamics simulations in biology.
Molecular dynamics--the science of simulating the motions of a system of particles--applied to biological macromolecules gives the fluctuations in the relative positions of the atoms in a protein or in DNA as a function of time. Knowledge of these motions provides insights into biological phenomena such as the role of flexibility in ligand binding and the rapid solvation of the electron transfer state in photosynthesis. Molecular dynamics is also being used to determine protein structures from NMR, to refine protein X-ray crystal structures faster from poorer starting models, and to calculate the free energy changes resulting from mutations in proteins.
1173. Adhesion receptors of the immune system.
The adhesive interactions of cells with other cells and with the extracellular matrix are crucial to all developmental processes, but have a central role in the functions of the immune system throughout life. Three families of cell-surface molecules regulate the migration of lymphocytes and the interactions of activated cells during immune responses.
1174. Activators and targets.
Proteins that activate genes are quite disparate in character; in particular, some work 'universally' and others do not. A simple model can accommodate most of the recently published results.
1180. Sex determination compared in Drosophila and Caenorhabditis.
Fruitflies and nematodes show many similarities in the general organization of the gene networks that control sexual dimorphism and dosage compensation. In contrast, the underlying molecular mechanisms appear to be very different in these two species. Developmental processes such as sex determination need not be strongly conserved in evolution.
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