Linkage disequilibrium in the human genome

With the availability of a dense genome-wide map of single nucleotide polymorphisms (SNPs), a central issue in human genetics is whether it is now possible to use linkage disequilibrium (LD) to map genes that cause disease. LD refers to correlations among neighbouring alleles, reflecting 'haplotypes' descended from single, ancestral chromosomes. The size of LD blocks has been the subject of considerable debate. Computer simulations and empirical data have suggested that LD extends only a few kilobases (kb) around common SNPs, whereas other data have suggested that it can extend much further, in some cases greater than 100 kb. It has been difficult to obtain a systematic picture of LD because past studies have been based on only a few (1-3) loci and different populations. Here, we report a large-scale experiment using a uniform protocol to examine 19 randomly selected genomic regions. LD in a United States population of north-European descent typically extends 60 kb from common alleles, implying that LD mapping is likely to be practical in this population. By contrast, LD in a Nigerian population extends markedly less far. The results illuminate human history, suggesting that LD in northern Europeans is shaped by a marked demographic event about 27,000-53,000 years ago.     

An auroral flare at Jupiter

Jupiter's aurora is the most powerful in the Solar System. It is powered largely by energy extracted from planetary rotation, although there seems also to be a contribution from the solar wind. This contrasts with Earth's aurora, which is generated through the interaction of the solar wind with the magnetosphere. The major features of Jupiter's aurora (based on far-ultraviolet, near-infrared and visible-wavelength observations) include a main oval that generally corotates with the planet and a region of patchy, diffuse emission inside the oval on Jupiter's dusk side. Here we report the discovery of a rapidly evolving, very bright and localized emission poleward of the northern main oval, in a region connected magnetically to Jupiter's outer magnetosphere. The intensity of the emission increased by a factor of 30 within 70 s, and then decreased on a similar timescale, all captured during a single four-minute exposure. This type of flaring emission has not previously been reported for Jupiter (similar, but smaller, transient events have been observed at Earth), and it may be related directly to changes in the solar wind.     

ICOS is essential for effective T-helper-cell responses

The outcome of T-cell responses after T-cell encounter with specific antigens is modulated by co-stimulatory signals, which are required for both lymphocyte activation and development of adaptive immunity. ICOS, an inducible co-stimulator with homology to CD28, is expressed on activated, but not resting T cells, and shows T-cell co-stimulatory function in vitro. ICOS binds specifically to its counter-receptor B7RP-1 (refs 5,6,7), but not to B7-1 or B7-2. Here we provide in vivo genetic evidence that ICOS delivers a co-stimulatory signal that is essential both for efficient interaction between T and B cells and for normal antibody responses to T-cell-dependent antigens. To determine the physiological function of ICOS, we generated and characterized gene-targeted ICOS-deficient mice. In vivo, a lack of ICOS results in severely deficient T-cell-dependent B-cell responses. Germinal centre formation is impaired and immunoglobulin class switching, including production of allergy-mediating IgE, is defective. ICOS-deficient T cells primed in in vivo and restimulated in vitro with specific antigen produce only low levels of interleukin-4, but remain fully competent to produce interferon-gamma.     

Bone marrow cells regenerate infarcted myocardium

Myocardial infarction leads to loss of tissue and impairment of cardiac performance. The remaining myocytes are unable to reconstitute the necrotic tissue, and the post-infarcted heart deteriorates with time. Injury to a target organ is sensed by distant stem cells, which migrate to the site of damage and undergo alternate stem cell differentiation; these events promote structural and functional repair. This high degree of stem cell plasticity prompted us to test whether dead myocardium could be restored by transplanting bone marrow cells in infarcted mice. We sorted lineage-negative (Lin-) bone marrow cells from transgenic mice expressing enhanced green fluorescent protein by fluorescence-activated cell sorting on the basis of c-kit expression. Shortly after coronary ligation, Lin- c-kitPOS cells were injected in the contracting wall bordering the infarct. Here we report that newly formed myocardium occupied 68% of the infarcted portion of the ventricle 9 days after transplanting the bone marrow cells. The developing tissue comprised proliferating myocytes and vascular structures. Our studies indicate that locally delivered bone marrow cells can generate de novo myocardium, ameliorating the outcome of coronary artery disease.     

Genetic linkage of ecological specialization and reproductive isolation in pea aphids

The evolution of ecological specialization generates biological diversity and may lead to speciation. Genetic architecture can either speed or retard this process. If resource use and mate choice have a common genetic basis through pleiotropy or close linkage, the resulting genetic correlations can promote the joint evolution of specialization and reproductive isolation, facilitating speciation. Here we present a model of the role of genetic correlations in specialization and speciation, and test it by analysing the genetic architecture of key traits in two highly specialized host races of the pea aphid (Acyrthosiphon pisum pisum; Hemiptera : Aphididae). We found several complexes of pleiotropic or closely linked quantitative trait loci (QTL) that affect key traits in ways that would promote speciation: QTL with antagonistic effects on performance on the two hosts are linked to QTL that produce asortative mating (through habitat choice). This type of genetic architecture may be common in taxa that have speciated under divergent natural selection.     

An arbuscular mycorrhizal fungus accelerates decomposition and acquires nitrogen directly from organic material

Arbuscular mycorrhizal fungi (order Glomales), which form mycorrhizal symbioses with two out of three of all plant species, are believed to be obligate biotrophs that are wholly dependent on the plant partner for their carbon supply. It is thought that they possess no degradative capability and that they are unable to decompose complex organic molecules, the form in which most soil nutrients occur. Earlier suggestions that they could exist saprotrophically were based on observation of hyphal proliferation on organic materials. In contrast, other mycorrhizal types have been shown to acquire nitrogen directly from organic sources. Here we show that the arbuscular mycorrhizal symbiosis can both enhance decomposition of and increase nitrogen capture from complex organic material (grass leaves) in soil. Hyphal growth of the fungal partner was increased in the presence of the organic material, independently of the host plant.     

Arthropod phylogeny based on eight molecular loci and morphology

The interrelationships of major clades within the Arthropoda remain one of the most contentious issues in systematics, which has traditionally been the domain of morphologists. A growing body of DNA sequences and other types of molecular data has revitalized study of arthropod phylogeny and has inspired new considerations of character evolution. Novel hypotheses such as a crustacean-hexapod affinity were based on analyses of single or few genes and limited taxon sampling, but have received recent support from mitochondrial gene order, and eye and brain ultrastructure and neurogenesis. Here we assess relationships within Arthropoda based on a synthesis of all well sampled molecular loci together with a comprehensive data set of morphological, developmental, ultrastructural and gene-order characters. The molecular data include sequences of three nuclear ribosomal genes, three nuclear protein-coding genes, and two mitochondrial genes (one protein coding, one ribosomal). We devised new optimization procedures and constructed a parallel computer cluster with 256 central processing units to analyse molecular data on a scale not previously possible. The optimal 'total evidence' cladogram supports the crustacean-hexapod clade, recognizes pycnogonids as sister to other euarthropods, and indicates monophyly of Myriapoda and Mandibulata.     

Rae1 and H60 ligands of the NKG2D receptor stimulate tumour immunity

Natural killer (NK) cells attack many tumour cell lines, and are thought to have a critical role in anti-tumour immunity; however, the interaction between NK cells and tumour targets is poorly understood. The stimulatory lectin-like NKG2D receptor is expressed by NK cells, activated CD8+ T cells and by activated macrophages in mice. Several distinct cell-surface ligands that are related to class I major histocompatibility complex molecules have been identified, some of which are expressed at high levels by tumour cells but not by normal cells in adults. However, no direct evidence links the expression of these 'induced self' ligands with tumour cell rejection. Here we demonstrate that ectopic expression of the murine NKG2D ligands Rae1beta or H60 in several tumour cell lines results in potent rejection of the tumour cells by syngeneic mice. Rejection is mediated by NK cells and/or CD8+ T cells. The ligand-expressing tumour cells induce potent priming of cytotoxic T cells and sensitization of NK cells in vivo. Mice that are exposed to live or irradiated tumour cells expressing Rae1 or H60 are specifically immune to subsequent challenge with tumour cells that lack NKG2D ligands, suggesting application of the ligands in the design of tumour vaccines.     

The timing of the last deglaciation in North Atlantic climate records

To determine the mechanisms governing the last deglaciation and the sequence of events that lead to deglaciation, it is important to obtain a temporal framework that applies to both continental and marine climate records. Radiocarbon dating has been widely used to derive calendar dates for marine sediments, but it rests on the assumption that the 'apparent age' of surface water (the age of surface water relative to the atmosphere) has remained constant over time. Here we present new evidence for variation in the apparent age of surface water (or reservoir age) in the North Atlantic ocean north of 40 degrees N over the past 20,000 years. In two cores we found apparent surface-water ages to be larger than those of today by 1,230 +/- 600 and 1,940 +/- 750 years at the end of the Heinrich 1 surge event (15,000 years BP) and by 820 +/- 430 to 1,010 +/- 340 years at the end of the Younger Dryas cold episode. During the warm B?lling-Aller?d period, between these two periods of large reservoir ages, apparent surface-water ages were comparable to present values. Our results allow us to reconcile the chronologies from ice cores and the North Atlantic marine records over the entire deglaciation period. Moreover, the data imply that marine carbon dates from the North Atlantic north of 40 degrees N will need to be corrected for these highly variable effects.     

Ancient chronology. Astronomical orientation of the pyramids

Spence speculates that Egypt's pyramid builders found true north by using a plumb line: when the stars Kochab and Mizar were seen on the same vertical, one was facing north. As evidence in support of this hypothesis, she points to the proposed interstar-line precession past the north celestial pole at a rate of 27' per century (cy). We argue that a mathematical error affects this result, which when corrected points more strongly to a different pair of stars. This suggests that the conventional ancient chronology, instead of being compressed, may actually have to be expanded slightly.