Gene expression divergence recapitulates the developmental hourglass model

The observation that animal morphology tends to be conserved during the embryonic phylotypic period (a period of maximal similarity between the species within each animal phylum) led to the proposition that embryogenesis diverges more extensively early and late than in the middle, known as the hourglass model. This pattern of conservation is thought to reflect a major constraint on the evolution of animal body plans. Despite a wealth of morphological data confirming that there is often remarkable divergence in the early and late embryos of species from the same phylum, it is not yet known to what extent gene expression evolution, which has a central role in the elaboration of different animal forms, underpins the morphological hourglass pattern. Here we address this question using species-specific microarrays designed from six sequenced Drosophila species separated by up to 40 million years. We quantify divergence at different times during embryogenesis, and show that expression is maximally conserved during the arthropod phylotypic period. By fitting different evolutionary models to each gene, we show that at each time point more than 80% of genes fit best to models incorporating stabilizing selection, and that for genes whose evolutionarily optimal expression level is the same across all species, selective constraint is maximized during the phylotypic period. The genes that conform most to the hourglass pattern are involved in key developmental processes. These results indicate that natural selection acts to conserve patterns of gene expression during mid-embryogenesis, and provide a genome-wide insight into the molecular basis of the hourglass pattern of developmental evolution.     

Origin of Columbia River flood basalt controlled by propagating rupture of the Farallon slab

The origin of the Steens-Columbia River (SCR) flood basalts, which is presumed to be the onset of Yellowstone volcanism, has remained controversial, with the proposed conceptual models involving either a mantle plume or back-arc processes. Recent tomographic inversions based on the USArray data reveal unprecedented detail of upper-mantle structures of the western USA and tightly constrain geodynamic models simulating Farallon subduction, which has been proposed to influence the Yellowstone volcanism. Here we show that the best-fitting geodynamic model depicts an episode of slab tearing about 17?million years ago under eastern Oregon, where an associated sub-slab asthenospheric upwelling thermally erodes the Farallon slab, leading to formation of a slab gap at shallow depth. Driven by a gradient of dynamic pressure, the tear ruptured quickly north and south and within about two million years covering a distance of around 900?kilometres along all of eastern Oregon and northern Nevada. This tear would be consistent with the occurrence of major volcanic dikes during the SCR-Northern Nevada Rift flood basalt event both in space and time. The model predicts a petrogenetic sequence for the flood basalt with sources of melt starting from the base of the slab, at first remelting oceanic lithosphere and then evolving upwards, ending with remelting of oceanic crust. Such a progression helps to reconcile the existing controversies on the interpretation of SCR geochemistry and the involvement of the putative Yellowstone plume. Our study suggests a new mechanism for the formation of large igneous provinces.     

Quality assessment of the human genome sequence

As the final sequencing of the human genome has now been completed, we present the results of the largest examination of the quality of the finished DNA sequence. The completed study covers the major contributing sequencing centres and is based on a rigorous combination of laboratory experiments and computational analysis.     

The DNA sequence and comparative analysis of human chromosome 5

Chromosome 5 is one of the largest human chromosomes and contains numerous intrachromosomal duplications, yet it has one of the lowest gene densities. This is partially explained by numerous gene-poor regions that display a remarkable degree of noncoding conservation with non-mammalian vertebrates, suggesting that they are functionally constrained. In total, we compiled 177.7 million base pairs of highly accurate finished sequence containing 923 manually curated protein-coding genes including the protocadherin and interleukin gene families. We also completely sequenced versions of the large chromosome-5-specific internal duplications. These duplications are very recent evolutionary events and probably have a mechanistic role in human physiological variation, as deletions in these regions are the cause of debilitating disorders including spinal muscular atrophy.     

CD3delta couples T-cell receptor signalling to ERK activation and thymocyte positive selection

Thymocytes from mice lacking the CD3delta chain of the T-cell receptor (TCR), unlike those of other CD3-deficient mice, progress from a CD4- CD8- double-negative to a CD4+ CD8+ double-positive stage. However, CD3delta-/- double-positive cells fail to undergo positive selection, by which double-positive cells differentiate into more mature thymocytes. Positive selection is also impaired in mice expressing inactive components of the Ras/mitogen activated protein (MAP) kinase signalling pathway. Here we show that CD3delta-/- thymocytes are defective in the induction of extracellular signal-regulated protein kinase (ERK) MAP kinases upon TCR engagement, whereas activation of other MAP kinases is unaffected. The requirement for CD3delta maps to its extracellular or transmembrane domains, or both, as expression of a tail-less CD3delta rescues both ERK activation and positive selection in CD3delta-/- mice. Furthermore, the defect correlates with severely impaired tyrosine phosphorylation of the linker protein LAT, and of the CD3zeta chain that is localized to membrane lipid rafts upon TCR engagement. Our data indicate that the blockade of positive selection of CD3delta-/- thymocytes may derive from defective tyrosine phosphorylation of CD3zeta in lipid rafts, resulting in impaired activation of the LAT/Ras/ERK pathway.     

Worst-Input Mutation Approach to Web Services Vulnerability Testing Based on SOAP Messages

The growing popularity and application of Web services have led to increased attention regarding the vulnerability of software based on these services. Vulnerability testing examines the trustworthiness and reduces the security risks of software systems. This paper proposes a worst-input mutation approach for testing Web service vulnerability based on Simple Object Access Protocol （SOAP） messages. Based on characteristics of SOAP messages, the proposed approach uses the farthest neighbor concept to guide generation of the test suite. The corresponding automatic test case generation algorithm, namely, the Test Case generation based on the Farthest Neighbor （TCFN）, is also presented. The method involves partitioning the input domain into sub-domains according to the number and type of SOAP message parameters in the TCFN, selecting the candidate test case whose distance is the farthest from all executed test cases, and applying it to test the Web service. We also implement and describe a prototype Web service vulnerability testing tool. The tool was applied to the testing of Web services on the Internet. The experimental results show that the proposed approach can find more vulnerability faults than other related approaches.     

Evolution of genes and genomes on the Drosophila phylogeny

Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.