95 research outputs found
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Seismological constraints on the down-dip shape of normal faults
We present a seismological technique for determining the down-dip shape of seismogenic normal faults. Synthetic models of non-planar source geometries reveal the important signals in teleseismic P and SH waveforms that are diagnostic of down-dip curvature. In particular, along-strike SH waveforms are the most sensitive to variations in source geometry, and have significantly more complex and larger-amplitude waveforms for curved source geometries than planar ones. We present the results of our forward-modelling technique for 13 earthquakes. Most continental normal-faulting earthquakes that rupture through the full seismogenic layer are planar and have dips of 30°–60°. There is evidence for faults with a listric shape from some of the earthquakes occurring in two regions; Tibet and East Africa. These ruptures occurred on antithetic faults, or minor faults within the hanging walls of the rifts affected, which may suggest a reason for the down-dip curvature. For these earthquakes, the change in dip across the seismogenic part of the fault plane is ≤30°.This work forms part of the NERC- and ESRC-funded project ‘Earthquakes without Frontiers’ and was partially supported by the NERC large grant ‘Looking inside the Continents from Space’
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Crustal Deformation and Fault Strength of the Sulawesi Subduction Zone
This paper investigates the seismicity and rheology of the North-Sulawesi subduction zone. Body-wave modeling is used to estimate focal mechanisms and centroid depths of moderate magnitude (M5–M6.5) earthquakes on the North Sulawesi megathrust and surrounding region. The slip vectors of megathrust earthquakes radiate outward from Sulawesi, indicating motion that is incompatible with the relative motion of two rigid plates. Instead, the observed deformation implies lateral spreading of high topography, controlled by gravitational potential energy contrasts. This finding suggests that the observed deformation of Sulawesi results from stresses transmitted through the lithosphere, rather than basal tractions due to circulation in the mantle. Our modeling of the force balance on the megathrust shows that the subduction megathrust is weak, with an average shear stress of ∼13 MPa and an effective coefficient of friction of 0.03. Elsewhere in Sulawesi, slip vectors of other earthquakes suggest similar potential-energy-driven deformation is present, but at significantly slower rates. Our results show the importance of lateral rheology contrasts in determining deformation rate, and hence seismic hazard, in response to a given driving force.Newton Institutional Links
Leverhulme Fellowshi
The origin of large molecules in primordial autocatalytic reaction networks
Large molecules such as proteins and nucleic acids are crucial for life, yet
their primordial origin remains a major puzzle. The production of large
molecules, as we know it today, requires good catalysts, and the only good
catalysts we know that can accomplish this task consist of large molecules.
Thus the origin of large molecules is a chicken and egg problem in chemistry.
Here we present a mechanism, based on autocatalytic sets (ACSs), that is a
possible solution to this problem. We discuss a mathematical model describing
the population dynamics of molecules in a stylized but prebiotically plausible
chemistry. Large molecules can be produced in this chemistry by the coalescing
of smaller ones, with the smallest molecules, the `food set', being buffered.
Some of the reactions can be catalyzed by molecules within the chemistry with
varying catalytic strengths. Normally the concentrations of large molecules in
such a scenario are very small, diminishing exponentially with their size.
ACSs, if present in the catalytic network, can focus the resources of the
system into a sparse set of molecules. ACSs can produce a bistability in the
population dynamics and, in particular, steady states wherein the ACS molecules
dominate the population. However to reach these steady states from initial
conditions that contain only the food set typically requires very large
catalytic strengths, growing exponentially with the size of the catalyst
molecule. We present a solution to this problem by studying `nested ACSs', a
structure in which a small ACS is connected to a larger one and reinforces it.
We show that when the network contains a cascade of nested ACSs with the
catalytic strengths of molecules increasing gradually with their size (e.g., as
a power law), a sparse subset of molecules including some very large molecules
can come to dominate the system.Comment: 49 pages, 17 figures including supporting informatio
A Measure of the Promiscuity of Proteins and Characteristics of Residues in the Vicinity of the Catalytic Site That Regulate Promiscuity
Promiscuity, the basis for the evolution of new functions through ‘tinkering’ of residues in the vicinity of the catalytic site, is yet to be quantitatively defined. We present a computational method Promiscuity Indices Estimator (PROMISE) - based on signatures derived from the spatial and electrostatic properties of the catalytic residues, to estimate the promiscuity (PromIndex) of proteins with known active site residues and 3D structure. PromIndex reflects the number of different active site signatures that have congruent matches in close proximity of its native catalytic site, the quality of the matches and difference in the enzymatic activity. Promiscuity in proteins is observed to follow a lognormal distribution (μ = 0.28, σ = 1.1 reduced chi-square = 3.0E-5). The PROMISE predicted promiscuous functions in any protein can serve as the starting point for directed evolution experiments. PROMISE ranks carboxypeptidase A and ribonuclease A amongst the more promiscuous proteins. We have also investigated the properties of the residues in the vicinity of the catalytic site that regulates its promiscuity. Linear regression establishes a weak correlation (R2∼0.1) between certain properties of the residues (charge, polar, etc) in the neighborhood of the catalytic residues and PromIndex. A stronger relationship states that most proteins with high promiscuity have high percentages of charged and polar residues within a radius of 3 Å of the catalytic site, which is validated using one-tailed hypothesis tests (P-values∼0.05). Since it is known that these characteristics are key factors in catalysis, their relationship with the promiscuity index cross validates the methodology of PROMISE
Why Is the Correlation between Gene Importance and Gene Evolutionary Rate So Weak?
One of the few commonly believed principles of molecular evolution is that functionally more important genes (or DNA sequences) evolve more slowly than less important ones. This principle is widely used by molecular biologists in daily practice. However, recent genomic analysis of a diverse array of organisms found only weak, negative correlations between the evolutionary rate of a gene and its functional importance, typically measured under a single benign lab condition. A frequently suggested cause of the above finding is that gene importance determined in the lab differs from that in an organism's natural environment. Here, we test this hypothesis in yeast using gene importance values experimentally determined in 418 lab conditions or computationally predicted for 10,000 nutritional conditions. In no single condition or combination of conditions did we find a much stronger negative correlation, which is explainable by our subsequent finding that always-essential (enzyme) genes do not evolve significantly more slowly than sometimes-essential or always-nonessential ones. Furthermore, we verified that functional density, approximated by the fraction of amino acid sites within protein domains, is uncorrelated with gene importance. Thus, neither the lab-nature mismatch nor a potentially biased among-gene distribution of functional density explains the observed weakness of the correlation between gene importance and evolutionary rate. We conclude that the weakness is factual, rather than artifactual. In addition to being weakened by population genetic reasons, the correlation is likely to have been further weakened by the presence of multiple nontrivial rate determinants that are independent from gene importance. These findings notwithstanding, we show that the principle of slower evolution of more important genes does have some predictive power when genes with vastly different evolutionary rates are compared, explaining why the principle can be practically useful despite the weakness of the correlation
Probing the Mutational Interplay between Primary and Promiscuous Protein Functions: A Computational-Experimental Approach
Protein promiscuity is of considerable interest due its role in adaptive metabolic plasticity, its fundamental connection with molecular evolution and also because of its biotechnological applications. Current views on the relation between primary and promiscuous protein activities stem largely from laboratory evolution experiments aimed at increasing promiscuous activity levels. Here, on the other hand, we attempt to assess the main features of the simultaneous modulation of the primary and promiscuous functions during the course of natural evolution. The computational/experimental approach we propose for this task involves the following steps: a function-targeted, statistical coupling analysis of evolutionary data is used to determine a set of positions likely linked to the recruitment of a promiscuous activity for a new function; a combinatorial library of mutations on this set of positions is prepared and screened for both, the primary and the promiscuous activities; a partial-least-squares reconstruction of the full combinatorial space is carried out; finally, an approximation to the Pareto set of variants with optimal primary/promiscuous activities is derived. Application of the approach to the emergence of folding catalysis in thioredoxin scaffolds reveals an unanticipated scenario: diverse patterns of primary/promiscuous activity modulation are possible, including a moderate (but likely significant in a biological context) simultaneous enhancement of both activities. We show that this scenario can be most simply explained on the basis of the conformational diversity hypothesis, although alternative interpretations cannot be ruled out. Overall, the results reported may help clarify the mechanisms of the evolution of new functions. From a different viewpoint, the partial-least-squares-reconstruction/Pareto-set-prediction approach we have introduced provides the computational basis for an efficient directed-evolution protocol aimed at the simultaneous enhancement of several protein features and should therefore open new possibilities in the engineering of multi-functional enzymes
Functional evolution of ADAMTS genes: Evidence from analyses of phylogeny and gene organization
BACKGROUND: The ADAMTS (A Disintegrin-like and Metalloprotease with Thrombospondin motifs) proteins are a family of metalloproteases with sequence similarity to the ADAM proteases, that contain the thrombospondin type 1 sequence repeat motifs (TSRs) common to extracellular matrix proteins. ADAMTS proteins have recently gained attention with the discovery of their role in a variety of diseases, including tissue and blood disorders, cancer, osteoarthritis, Alzheimer's and the genetic syndromes Weill-Marchesani syndrome (ADAMTS10), thrombotic thrombocytopenic purpura (ADAMTS13), and Ehlers-Danlos syndrome type VIIC (ADAMTS2) in humans and belted white-spotting mutation in mice (ADAMTS20). RESULTS: Phylogenetic analysis and comparison of the exon/intron organization of vertebrate (Homo, Mus, Fugu), chordate (Ciona) and invertebrate (Drosophila and Caenorhabditis) ADAMTS homologs has elucidated the evolutionary relationships of this important gene family, which comprises 19 members in humans. CONCLUSIONS: The evolutionary history of ADAMTS genes in vertebrate genomes has been marked by rampant gene duplication, including a retrotransposition that gave rise to a distinct ADAMTS subfamily (ADAMTS1, -4, -5, -8, -15) that may have distinct aggrecanase and angiogenesis functions
Evidence for Loss of a Partial Flagellar Glycolytic Pathway during Trypanosomatid Evolution
Classically viewed as a cytosolic pathway, glycolysis is increasingly recognized as a metabolic pathway exhibiting surprisingly wide-ranging variations in compartmentalization within eukaryotic cells. Trypanosomatid parasites provide an extreme view of glycolytic enzyme compartmentalization as several glycolytic enzymes are found exclusively in peroxisomes. Here, we characterize Trypanosoma brucei flagellar proteins resembling glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and phosphoglycerate kinase (PGK): we show the latter associates with the axoneme and the former is a novel paraflagellar rod component. The paraflagellar rod is an essential extra-axonemal structure in trypanosomes and related protists, providing a platform into which metabolic activities can be built. Yet, bioinformatics interrogation and structural modelling indicate neither the trypanosome PGK-like nor the GAPDH-like protein is catalytically active. Orthologs are present in a free-living ancestor of the trypanosomatids, Bodo saltans: the PGK-like protein from B. saltans also lacks key catalytic residues, but its GAPDH-like protein is predicted to be catalytically competent. We discuss the likelihood that the trypanosome GAPDH-like and PGK-like proteins constitute molecular evidence for evolutionary loss of a flagellar glycolytic pathway, either as a consequence of niche adaptation or the re-localization of glycolytic enzymes to peroxisomes and the extensive changes to glycolytic flux regulation that accompanied this re-localization. Evidence indicating loss of localized ATP provision via glycolytic enzymes therefore provides a novel contribution to an emerging theme of hidden diversity with respect to compartmentalization of the ubiquitous glycolytic pathway in eukaryotes. A possibility that trypanosome GAPDH-like protein additionally represents a degenerate example of a moonlighting protein is also discussed
The self-organizing fractal theory as a universal discovery method: the phenomenon of life
A universal discovery method potentially applicable to all disciplines studying organizational phenomena has been developed. This method takes advantage of a new form of global symmetry, namely, scale-invariance of self-organizational dynamics of energy/matter at all levels of organizational hierarchy, from elementary particles through cells and organisms to the Universe as a whole. The method is based on an alternative conceptualization of physical reality postulating that the energy/matter comprising the Universe is far from equilibrium, that it exists as a flow, and that it develops via self-organization in accordance with the empirical laws of nonequilibrium thermodynamics. It is postulated that the energy/matter flowing through and comprising the Universe evolves as a multiscale, self-similar structure-process, i.e., as a self-organizing fractal. This means that certain organizational structures and processes are scale-invariant and are reproduced at all levels of the organizational hierarchy. Being a form of symmetry, scale-invariance naturally lends itself to a new discovery method that allows for the deduction of missing information by comparing scale-invariant organizational patterns across different levels of the organizational hierarchy
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