This Week in Science

Science  11 Mar 2011:
Vol. 331, Issue 6022, pp. 1239
  1. Watching Splicing Live


      The spliceosome, which excises introns from precursors to messenger RNAs (pre-mRNAs), is a highly dynamic macromolecular machine consisting of five RNAs and scores of both core and accessory proteins. To overcome the difficulties of fully reconstituting the spliceosome from its purified components, Hoskins et al. (p. 1289) followed its assembly in yeast using colocalization single-molecule spectroscopy (CoSMoS) in unfractionated cell extracts. Their kinetic analysis reveals that the spliceosome assembles by first binding U1 small nuclear RNA followed by U2, U4/U6.U5, and then the multiprotein Prp19-complex. No single subcomplex binding event limits the overall assembly rate, and the commitment of the pre-mRNA molecule to splicing progressively increases as the spliceosome assembles.

    1. Prehistoric Social Networking

        A hunter-gatherer life-style is thought to have been the predominant social structure for most of human history. The common assumption is that hunter-gatherer groups consisted largely of related individuals: parents, siblings, offspring, and possibly extending to include spousal relations. Hill et al. (p. 1286; see the Perspective by Chapais) have analyzed the kin relationships of groups in 32 contemporary hunter-gatherer societies and surprisingly find that most members of a group are not related to each other. Although siblings may often be co-resident, neither matrilineal nor patrilineal organization dominates. The occurrence of networks of interacting yet genetically unrelated individuals has implications for theories about the origins of prosocial behavior and of culture.

      1. Tomcod Toxicology

          From 1947 to 1976, two General Electric manufacturing facilities released around 600,000 kg of polychlorinated biphenyls (PCBs) into the Hudson River, NY, USA. Atlantic tomcod in the river accumulated some of the highest levels of PCBs ever seen in natural populations and became resistant to the poisonous effects of the contamination. The toxic effects of PCBs are usually mediated by cytochrome P4501A, which is regulated by the aryl hydrocarbon receptor (AHR), but the Hudson River tomcod population show poor inducibility of cytochrome P4501A. Wirgin et al. (p. 1322, published online 17 February) found that the Hudson River tomcod AHR2 gene had four distinct polymorphisms, but a two–amino acid deletion was found to reduce the ability of the AHR2-1 allele to bind PCBs and appears to be the basis of the fish's resistance to poisoning. The presence of this allele at low frequencies in tomcod from nearby, cleaner, rivers indicates that AHR2-1 was also present at low frequency in the Hudson River tomcod before the contamination event and was very rapidly selected for after the PCB leak.

        1. Add Water to Dry

            The intertropical convergence zone, the globe-circling region where winds from the Northern and Southern hemispheres converge near the equator, is where most tropical rainfall occurs. The position of this region is variable on seasonal time scales, as well as on longer ones, being particularly susceptible to the effects of large-scale climate perturbations. Stager et al. (p. 1299, published online 24 February) connect one of these major perturbations with a concurrent widespread and severe drought in Africa. Large volumes of glacial meltwater and ice that entered the North Atlantic between 15,000 and 18,000 years ago shifted the convergence zone further south, thus depriving that region of Africa of the moisture that it received so abundantly both before and after that period.

          1. Another Example of Frustration

              Geometry can be used to create frustrated systems (that is, those that do not pack in configurations of minimum energy), such as block copolymers, where two or more polymer molecules are forced to be near each other through a covalent chemical bond. Zeng et al. (p. 1302; see the cover) examine liquid crystalline rod-like molecules with two incompatible side groups that pack into honeycomb structures and form complex tiling patterns. Upon heating, a reversible phase transition is observed from a phase-separated state to a mixed one, in a transition analogous to the Curie transition in simple and frustrated ferro- and antiferromagnets.

            1. A Silicon Rhombus

                CREDIT: SUZUKI ET AL.

                Unlike carbon atoms, silicon atoms tend not to engage in π-bonding in their natural compounds. By using bulky groups to force the silicon atoms into close proximity while inhibiting their reactivity toward other molecules nearby, Suzuki et al. (p. 1306; see the Perspective by Apeloig) have synthesized and structurally characterized a silicon analog of cyclobutadiene, the strained, π-bonded tetragonal hydrocarbon that exhibits anti-aromaticity. Whereas the carbon compound compensates for its electronic instability by lengthening and shortening its bonds in alternation, the four Si-Si bonds adopt essentially equal lengths. Instead, the silicon centers vary their angular disposition, and theoretical calculations support an accompanying variation in their charge polarizations.

              1. Turing Patterns in 3D

                  Turing patterns—self-organized structures created by systems that undergo reaction and diffusion—are a possible mechanism underlying pattern formation in living organisms. Although there are many experimental studies of two-dimensional (2D) pattern formation—three-dimensional (3D) structures, the most relevant to biology, have been difficult to observe and should, according to theoretical studies, show even richer patterns. Using tomographic methods, Bánsági et al. (p. 1309, published online 10 February) demonstrate the existence of patterns that are inherently 3D, as opposed to simple extensions of 2D patterns, in a reaction-diffusion system known as the Belousov-Zhabotinsky reaction, running in a microemulsion.

                1. Metabolic Lags

                    Jet travel and working the night shift uncouple patterns of eating and activity from the body's internal circadian clock. Recent evidence indicates that such disruption of circadian rhythms has deleterious consequences for metabolic control and can increase the occurrence of diseases like obesity or diabetes. Feng et al. (p. 1315; see the Perspective by Moore) provide insight into the molecular mechanisms that couple circadian rhythms to metabolic control in the liver. The authors found that histone deacetylase 3 (HDAC3) bound to over 14,000 genes throughout the genome during the day when mice were inactive but only to about 100 genes during the night when the animals were active and feeding. Genes with products that function in liver metabolism tended to bind HDAC3, and the presence of HDAC3 was associated with histone deacetylation and decreased transcription. Thus, failure to coordinate expression of such genes with feeding and activity may contribute to the observed effects of circadian disruption on metabolism.

                  1. Tissues Simply

                      CREDIT: DANIEL J. DICKINSON

                      The identification of shared genes and derived characteristics among distantly related organisms help us to understand how cells and tissues are organized and how this organization evolved. Dickinson et al. (p. 1336) have discovered that unicellular organisms capable of social organization, such as the amoeba Dictyostelium discoideum, can differentiate cells into simple tissues. Dictyostelium epithelium is composed of a single layer of elongated polarized cells necessary for the formation of the fruiting body. The organization, morphology, and function of Dictyostelium epithelium are dependent on an ancestral signaling pathway that is comprised of the functional orthologs of α- and β-catenins, but that does not require Wnt signaling nor cadherins.

                    1. Bacterial-Host Exploitation

                        Intracellular bacterial pathogens are responsible for a variety of diseases, including listeriosis and legionnaire's disease. The bacterial pathogens subvert cellular functions through the interaction of bacterial effector proteins with host components. Lebreton et al. (p. 1319; published online 20 January; see the Perspective by Rohde) found that a virulence factor, LntA, of the bacterial pathogen Listeria monocytogenes targets the host cell nucleus to activate the type III–interferon signaling pathway. LntA counteracted the repression mediated by the chromatin regulator BAHD1 to subvert the heterochromatin machinery and reprogram the transcription of host genes involved in innate immunity. The pathogens thus manipulate epigenetic regulation to their advantage.

                      1. Feeling the Heat

                          Given a choice, a fruit fly will seek a temperature optimum of 18°C. This behavior requires a biochemical signaling pathway apparently initiated by a heterotrimeric guanine nucleotide–binding protein (G protein)–coupled receptor. Given the similarity of these signaling events to those initiated by rhodopsin, the G protein–coupled receptor that senses light, Shen et al. (p. 1333; see the Perspective by Minke and Peters) tested the effects of rhodopsin mutations on temperature selection in flies and, surprisingly, found that it resulted in discrimination between temperatures within a few degrees of the the optimal 18°C, independent of light sensation. One or more accessory molecules may also be required, as the rhodopsin molecule itself does not seem to be the temperature sensor.

                        1. Casually Causal Learning

                            Children are amazing learners, and how this happens is a question that has nourished several disciplines. Tenenbaum et al. (p. 1279) review recent developments in the frameworks used for studying how humans learn concepts and causal relations. Abstract concepts provide organizing schemes within which new information can be examined and by which a judgment can be formed about whether the existing scheme need be expanded or even discarded in favor of a new one. Causal learning can be seen as the imposition of a selected set of relations on concepts, which again can be regarded as provisional, depending on the acquisition of new data and testing for consistency. Formal mathematical models, such as those reviewed, offer the promise of more discoveries about the neural bases for cognition.

                          1. Organic Aerosol Blowout

                              On 20 April 2010, the Deepwater Horizon drilling installation began to spew enormous quantities of crude oil into the Gulf of Mexico. Much of the oil that escaped floated to the sea surface, where it began to evaporate. Based on airborne measurements of the gaseous and aerosol composition of air above the oil spill, de Gouw et al. (p. 1295; see the Perspective by Coe) demonstrate the heretofore poorly documented importance of compounds of intermediate volatility in secondary organic compounds in secondary organic aerosol formation, a process that has been suggested to be a significant source of organic aerosols in the atmosphere.

                            1. Lining Up for Photoreactions

                                Conjugated organic molecules can photodimerize in solution, but some reaction products may not be observed. For example, the substituted anthracene, 9-phenylethynylanthracene, can form six-membered rings (a 4 + 2 addition) but not eight-membered rings (a 4 + 4 addition). Kim et al. (p. 1312) show that a sulfur-bearing derivative of this molecule, absorbed in defects within alkane thiolate monolayers on gold, can orient so that it undergoes ultraviolet photodimerization reactions that produce the 4 + 4 reaction product.

                              1. Aping Aging

                                  Human beings are considered distinct from other primates for a host of traits, including how we age. A long-term study of several primate groups in their natural habitat by Bronikowski et al. (p. 1325) provided life history parameters for aging of many primates, which were then compared with those of humans. The general life history pattern of humans seems not exceptional after all and falls within the parameters found for primates in general. However, human males do show unusually low mortality rates compared with other primate males, but even this is consistent with the general finding that males of monogamous species age more slowly than males of polygynous ones. Finally, aging patterns across primate species showed no relationship to phylogeny, indicating that aging patterns are evolutionarily labile.

                                1. Relax, Uncoil

                                    During replication, the DNA helix has to be partially unwound, requiring enzymes called topoisomerases, to relax DNA coils and then to rewind them. As a result, the strands of DNA tangle into catenanes that must be removed before cell division can be completed. Baxter et al. (p. 1328) used yeast centromeric plasmids to probe the events preceding decatenation. They found that as the mitotic spindles form and attach to the chromosomes' kinetochores, a topological transition is initiated that throws the DNA into positive supercoils. The geometry of the positive supercoils allows maximal activity of topoisomerase II, which disentangles any intertwining between the DNA strands and ensures that they can be equally partitioned between the daughter cells.