Understanding hierarchical protein evolution from first principles.

We propose a model that explains the hierarchical organization of proteins in fold families. The model, which is based on the evolutionary selection of proteins by their native state stability, reproduces patterns of amino acids conserved across protein families. Due to its dynamic nature, the model sheds light on the evolutionary time-scales. By studying the relaxation of the correlation function between consecutive mutations at a given position in proteins, we observe separation of the evolutionary time-scales: at short time intervals families of proteins with similar sequences and structures are formed, while at long time intervals the families of structurally similar proteins that have low sequence similarity are formed. We discuss the evolutionary implications of our model. We provide a "profile" solution to our model and find agreement between predicted patterns of conserved amino acids and those actually observed in nature.     

Morphological evolution: Estimation principles, patterns, and mechanisms

Directions, modes, specializations, and coordination systems of morphofunctional changes are discussed based on modern data. Phylogenetic heterochronies (pedomorphoses and outstripping), which provide the basis for parallel, mosaic, and saltation development and different rates of morphological evolution, are regarded as important events of morphological diversification. The analysis of specificity and relationships of structural levels of organization (including genetic and epigenetic) and the elaboration of evolutionary principles of their dynamic stability are thought to be the most promising fields of modern research.     

Biophysical modeling of radiation induced genetic damage to cells

The paper deals with the new approach for high accurate prediction of ionising radiation induced lesions of the cellular genetic structures. The previous techniques mainly were based on the assumption of the random radiation-induced breakage of the cellular DNA. They did not consider higher-order DNA organisation in the chromatin and in the interphase chromosomes. The paper discusses the new methods of the biophysical modelling of DNA breakage following high LET irradiation which takes into account the information on 3-dimensional structural organisation of DNA in interphase chromosomes. On this basis the influence of DNA organisation in the chromosomes on both dsb clusters induction and on repair were quantitatively studied, that was impossible by the means of previous computational techniques.     

Spatial and temporal patterns in the activity of European moles

 Using ratio-tracking data obtained at three sites, we assessed the effects of season and of neighbour avoidance on the activity and patterns of home range use by European moles (Talpa europaea). The home ranges of non-breeding male and female moles did not differ significantly in size, and averaged 2324 m² (minimum convex polygon). Although overlap between ranges was small (an average of 12.8% of each range being shared with neighbours and an average of only 3.3% of 2×2 m grid cells were shared with an individual neighbour, ranges were not oriented to avoid neighbours. Non-breeding male/female neighbours tended to share more of their grid cells (3.9±5.7%) mean ±SD than did neighbours of the same sex (male:male 1.2±0.95%; female:female 1.1±1.3%), but there was no significant difference in overlap between any combination of sex pairings. On average, each mole spent only 0.9% of its time within 6 m of another mole, and only 3 out of 46 dyads showed evidence of being attracted to each other; there was no evidence from the simultaneous movement patterns of neighbouring moles that they avoided each other. Although moles tended to return to the same part of their range at the same time on successive days, there was also some indication of gradual changes in the spatial pattern of daily home range use. Moles had a triphasic pattern of activity, but this became tetraphasic under drought conditions. There were significant differences between sites, but not between sexes, in sleeping behaviour and activity patterns. These differences could be related to seasonal differences in soil moisture and thus probably to prey renewal rates. We conclude that in our sites, the activity patterns and movements of moles depend on the temporal and spatial dispersion of food, rather than on short-term interactions between the movements of neighbours. Received: 13 January 1996 / Accepted: 26 June 1996     

Calculation of isotope effects from first principles

Various means of calculating the effect of changing the mass of a given atom upon a chemical process are reviewed. Of particular interest is the deuterium isotope effect comparing the normal protium nucleus with its heavier deuterium congener. The replacement of the bridging protium in a neutral hydrogen bond such as the water dimer by a deuterium strengthens the interaction by a small amount via effects upon the vibrational energy. In an ionic H-bond such as the protonated water dimer, on the other hand, the reverse trend is observed in that replacement of the bridging protium by dimer weakens the interaction. In addition to the stability of a given complex, the rate at which a proton transfers from one group to another is likewise affected by deuterium substitution, viz. kinetic isotope effects (KIEs). The KIE is enlarged as the temperature drops, particularly so if the calculation of KIE includes proton tunneling. The KIE is also sensitive to any angular distortions or stretches present in the H-bond of interest. KIEs can be computed either by the standard transition state theory which is derived via only two points on the potential energy surface, or by more complete formalisms which take account of larger swaths of the surface. While more time intensive, the latter can also be applied to provide insights important in interpretation of experimental data.     

Imitational modeling of evolution: from organic macromolecules to protocell and animal cell

A dynamic imitational model is developed of initial stages of cell evolution based on role of environmental cation concentration. The model is developed on our hypothesis, concerning the medium of the appearance of protocells. Could be potassium water reservoirs rather than sea salt water with its predominance of sodium salts. The necessary elements of appearance the protocells served organic molecules, code of their synthesis, and formation of macromolecules under favorable ion concentration in environment High K+ and Mg2+ concentration and bow Na+. The model is based on an assumption that one of the first stages in evolution of life was the appearance in potassium-magnesium water reservoirs of organic molecules capable for selfreplication on the basis of genetic code and formation of protocells with potassium cytoplasm. The model has demonstrated necessity of formation of cell envelope for development of the protocell. Replacement of the dominant cation in water reservoirs-potassium by sodium-required the appearance of ion-transporting devices in plasma membrane and their participation in adaptation of cells to environment. This stage of evolution was accompanied by the most important morpho-functional event--formation of the plasma membrane instead of cell envelope. The membrane provided the ion asymmetry in the cell (preservation of K+ in it) relatively to the sodium external medium for maintaining optimal intracellular medium. In the model system, predecessors of animal cells elaborated mechanism of maintenance of the potassium cytoplasm with the sodium counter-ion dominating in the environment.     

Convergence and divergence in the evolution of cat skulls: temporal and spatial patterns of morphological diversity

Background

Studies of biological shape evolution are greatly enhanced when framed in a phylogenetic perspective. Inclusion of fossils amplifies the scope of macroevolutionary research, offers a deep-time perspective on tempo and mode of radiations, and elucidates life-trait changes. We explore the evolution of skull shape in felids (cats) through morphometric analyses of linear variables, phylogenetic comparative methods, and a new cladistic study of saber-toothed cats.

Methodology/Principal Findings

A new phylogenetic analysis supports the monophyly of saber-toothed cats (Machairodontinae) exclusive of Felinae and some basal felids, but does not support the monophyly of various saber-toothed tribes and genera. We quantified skull shape variation in 34 extant and 18 extinct species using size-adjusted linear variables. These distinguish taxonomic group membership with high accuracy. Patterns of morphospace occupation are consistent with previous analyses, for example, in showing a size gradient along the primary axis of shape variation and a separation between large and small-medium cats. By combining the new phylogeny with a molecular tree of extant Felinae, we built a chronophylomorphospace (a phylogeny superimposed onto a two-dimensional morphospace through time). The evolutionary history of cats was characterized by two major episodes of morphological divergence, one marking the separation between saber-toothed and modern cats, the other marking the split between large and small-medium cats.

Conclusions/Significance

Ancestors of large cats in the ‘Panthera’ lineage tend to occupy, at a much later stage, morphospace regions previously occupied by saber-toothed cats. The latter radiated out into new morphospace regions peripheral to those of extant large cats. The separation between large and small-medium cats was marked by considerable morphologically divergent trajectories early in feline evolution. A chronophylomorphospace has wider applications in reconstructing temporal transitions across two-dimensional trait spaces, can be used in ecophenotypical and functional diversity studies, and may reveal novel patterns of morphospace occupation.     

Spatial effects favour the evolution of niche construction

We present an individual-based, spatial implementation of an existing two-locus population genetic model of niche construction. Our analysis reveals that, across a broad range of conditions, niche-construction traits can drive themselves to fixation by simultaneously generating selection that favours 'recipient' trait alleles and linkage disequilibrium between niche-construction and recipient trait alleles. The effect of spatiality is key, since it is the local, resource-mediated interaction between recipient and niche-constructing loci which gives rise to gene linkage. Spatial clustering effects point to a possible mechanism by which an initially rare recipient trait whose selection depends on niche construction could establish in an otherwise hostile environment. The same mechanism could also lead to the spread of an established niche-constructing colony. Similar phenomena are observed in the spatial modelling of two species 'engineering webs'. Here, the activities of two niche-constructing species can combine to drive a particular recipient trait to fixation, or in certain circumstances, maintain the presence of polymorphisms through the preservation of otherwise deleterious alleles. This may have some relevance to ecosystem stability and the maintenance of genetic variation, where the frequencies of key resources are affected by the niche-constructing activities of more than one species. Our model suggests that the stability of multi-species webs in natural populations may increase as the complexity of species-environment interactions increases.     

Negative niche construction favors the evolution of cooperation

By benefitting others at a cost to themselves, cooperators face an ever present threat from defectors—individuals that avail themselves of the cooperative benefit without contributing. A longstanding challenge to evolutionary biology is to understand the mechanisms that support the many instances of cooperation that nevertheless exist. In spatially-structured environments, clustered cooperator populations reach greater densities, which creates more mutational opportunities to gain beneficial non-social adaptations. Hammarlund et al. recently demonstrated that cooperation rises in abundance by hitchhiking with these non-social mutations. However, once adaptive opportunities have been exhausted, the ride abruptly ends as cooperators are displaced by adapted defectors. Using an agent-based model, we demonstrate that the selective feedback that is created as populations construct their local niches can maintain cooperation at high proportions and even allow cooperators to invade. This cooperator success depends specifically on negative niche construction, which acts as a perpetual source of adaptive opportunities. As populations adapt, they alter their environment in ways that reveal additional opportunities for adaptation. Despite being independent of niche construction in our model, cooperation feeds this cycle. By reaching larger densities, populations of cooperators are better able to adapt to changes in their constructed niche and successfully respond to the constant threat posed by defectors. We relate these findings to previous studies from the niche construction literature and discuss how this model could be extended to provide a greater understanding of how cooperation evolves in the complex environments in which it is found.     

DNA hybridization in animal taxonomy: a critique from first principles

DNA hybridization is a "distance method" for phylogenetic reconstruction and, as such, shares a set of assumptions, advantages, and problems with other techniques that do not directly employ character data. The technique purports to measure the average percent mismatch of homologous nucleotide sequences between the single-copy genomes of species. This measurement, as any other, is subject to considerations of accuracy and precision. While replicate measurements and technical modifications can improve precision, the accuracy of such measurements is limited by the equivalence of genomes under comparison. Such routine events in genome evolution as gene duplication and deletion may complicate the interpretation of DNA hybridization distances. Beyond measurement limitations, the most serious potential distortions of distances are due to biased sequence sampling and homoplasy. These problems, however, do not necessarily preclude phylogenetic reconstruction, and their effects may be mitigated by numerical corrections. Homoplasy, in particular, is a difficulty faced by all methods of phylogenetic inference. If such distortions can be eliminated, mitigated by correction, or shown to be trivial, pairwise tree-construction strategies should provide reliable estimates of phylogeny.     

Biophysical functionality in polysaccharides: from Lego-blocks to nano-particles

The objective of the paper is to show the very important biophysical concepts that have been developed with polysaccharides. In particular, an attempt will be made to relate “a posteriori” the fundamental aspects, both experimental and theoretical, with some industrial applications of polysaccharide-based materials. The overview of chain conformational aspects includes relationships between topological features and local dynamics, exemplified for some naturally occurring carbohydrate polymers. Thus, by using simulation techniques and computational studies, the physicochemical properties of aqueous solutions of polysaccharides are interpreted. The relevance of conformational disorder–order transitions, chain aggregation, and phase separation to the underlying role of the ionic contribution to these processes is discussed. We stress the importance of combining information from analysis of experimental data with that from statistical–thermodynamic models for understanding the conformation, size, and functional stability of industrially important polysaccharides. The peculiar properties of polysaccharides in industrial applications are summarized for the particularly important example of nanoparticles production, a field of growing relevance and scientific interest.     

Contrasting patterns in trophic niche evolution of polymorphic Arctic charr populations in two subarctic Norwegian lakes

Hydrobiologia - Lipid biomarkers in sediments, which are indicative of biological production, provide important information regarding the environmental conditions in and around lakes, and can be...     

Design of thyroid hormone receptor antagonists from first principles

It is desirable to obtain TR antagonists for treatment of hyperthyroidism and other conditions. We have designed TR antagonists from first principles based on TR crystal structures. Since agonist ligands are buried in the fold of the TR ligand binding domain (LBD), we reasoned that ligands that resemble agonists with large extensions should bind the LBD, but would prevent its folding into an active conformation. In particular, we predicted that extensions at the 5′ aryl position of ligand should reposition helix (H) 12, which forms part of the co-activator binding surface, and thereby inhibit TR activity. We have found that some synthetic ligands with 5′ aryl ring extensions behave as antagonists (DIBRT, NH-3), or partial antagonists (GC-14, NH-4). Moreover, one compound (NH-3) represents the first potent TR antagonist with nanomolar affinity that also inhibits TR action in an animal model. However, the properties of the ligands also reveal unexpected aspects of TR behavior. While nuclear receptor antagonists generally promote binding of co-repressors, NH-3 blocks co-activator binding and also prevents co-repressor binding. More surprisingly, many compounds with extensions behave as full or partial agonists. We present hypotheses to explain both behaviors in terms of dynamic equilibrium of H12 position.     

The evolution of temporal patterns of selfishness, altruism, and group cohesion

In intrademic selection models, individuals interact in groups, and this interaction phase is usually treated as a point in time. It is likely, however, that interactions take place over some time period. If selfishness is treated as a quantitative trait and this time period is explicitly considered, how does the evolutionarily stable strategy (ESS) level of selfishness or altruism change through time? Our main result is that, under biologically reasonable conditions, the ESS level of selfishness is expected to increase. Two of the assumptions behind this result are that there is a finite time horizon on the life of the group and that reproduction occurs continuously throughout the time period in question. If there is no time horizon or if all reproductive output is concentrated at the end of the time period, the ESS level of selfishness is constant. Our main result suggests that care must be taken when interpreting empirical data that is collected at different times and that altruism will often be most pronounced when groups first form. The model also demonstrates that, when individuals interact repeatedly over time, the evolution of altruism can be promoted through a mechanism other than reciprocity.     

Biophysical models of the heart electrical activity

Based on the fundamental knowledge of the space-temporal organization of extracellular electrical fields of the myocardium, a system for 3-D computer modeling of the cardiac electrical activity at different structural levels of the object is being developed at the Institute of Theoretical and Experimental Biophysics. The system is based on the earlier proposed and modified biophysical model of the electrocardiosignal genesis represented by a double electrical layer along the surface of the electrically active myocardium. The system combines the model for activation and repolarization of the heart ventricles; the advanced model for the evaluation of parameters of the cardiac electric field, which makes it possible to derive model electrocardiosignals both in the direct regime of calculation of the potentials and in the regime of calculation of electrocardiosignals from preliminarily determined components of the multipole equivalent electrical heart generator; a database for the model parameters and their combinations in the form of cards of simulated "patients", and a database of modeled electrocardiosignals. In the present paper (first from three within the framework of the problem), simulation methods in electrocardiology are briefly described and a biophysical model of the heart electrical activity is presented, which has made up the basis of the system for computer modeling of forward and inverse problems of the cardiac electric field. The parameters of the model are electrophysiological, anatomical, and biophysical characteristics of the heart.     

The nocturnal bottleneck and the evolution of activity patterns in mammals

In 1942, Walls described the concept of a ‘nocturnal bottleneck’ in placental mammals, where these species could survive only by avoiding daytime activity during times in which dinosaurs were the dominant taxon. Walls based this concept of a longer episode of nocturnality in early eutherian mammals by comparing the visual systems of reptiles, birds and all three extant taxa of the mammalian lineage, namely the monotremes, marsupials (now included in the metatherians) and placentals (included in the eutherians). This review describes the status of what has become known as the nocturnal bottleneck hypothesis, giving an overview of the chronobiological patterns of activity. We review the ecological plausibility that the activity patterns of (early) eutherian mammals were restricted to the night, based on arguments relating to endothermia, energy balance, foraging and predation, taking into account recent palaeontological information. We also assess genes, relating to light detection (visual and non-visual systems) and the photolyase DNA protection system that were lost in the eutherian mammalian lineage. Our conclusion presently is that arguments in favour of the nocturnal bottleneck hypothesis in eutherians prevail.     

Ecological niche modeling to estimate the distribution of Japanese encephalitis virus in Asia

Background

Culex tritaeniorhynchus is the primary vector of Japanese encephalitis virus (JEV), a leading cause of encephalitis in Asia. JEV is transmitted in an enzootic cycle involving large wading birds as the reservoirs and swine as amplifying hosts. The development of a JEV vaccine reduced the number of JE cases in regions with comprehensive childhood vaccination programs, such as in Japan and the Republic of Korea. However, the lack of vaccine programs or insufficient coverage of populations in other endemic countries leaves many people susceptible to JEV. The aim of this study was to predict the distribution of Culex tritaeniorhynchus using ecological niche modeling.

Methods/Principal Findings

An ecological niche model was constructed using the Maxent program to map the areas with suitable environmental conditions for the Cx. tritaeniorhynchus vector. Program input consisted of environmental data (temperature, elevation, rainfall) and known locations of vector presence resulting from an extensive literature search and records from MosquitoMap. The statistically significant Maxent model of the estimated probability of Cx. tritaeniorhynchus presence showed that the mean temperatures of the wettest quarter had the greatest impact on the model. Further, the majority of human Japanese encephalitis (JE) cases were located in regions with higher estimated probability of Cx. tritaeniorhynchus presence.

Conclusions/Significance

Our ecological niche model of the estimated probability of Cx. tritaeniorhynchus presence provides a framework for better allocation of vector control resources, particularly in locations where JEV vaccinations are unavailable. Furthermore, this model provides estimates of vector probability that could improve vector surveillance programs and JE control efforts.