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Invertebrate recognition protein cross-reacts with an immunoglobulin idiotype.

To estimate the minimal structural requirements for cross-reaction of idiotypic determinants, we determined the capacity of monoclonal antibodies specific for the idiotype of the phosphorylcholine (PC)-binding myeloma protein TEPC-15 for cross-reactivities with the PC-binding, acute-phase protein C-reactive protein (CRP) and the hemagglutinin from the horseshoe crab Limulus polyphemus (limulin), which binds sialic acid and PC. Certain monoclonal antibodies (MAb) to the TEPC-15 idiotype showed strong cross-reactions with CRP and limulin when tested by enzyme-linked immunoadsorbent assays. The specificity of the cross-reactivities was confirmed by testing the binding of the reactive anti-TEPC-15 MAb to both CRP and limulin in the presence of p-nitrophenylphosphorylcholine (pNPPC), N-acetylneuraminic acid, and bovine submaxillary mucin. The binding of the MAb to both CRP and limulin was strongly decreased by pNPPC, partially decreased by free PC, and not affected by N-acetylneuraminic acid or bovine submaxillary mucin. Neither CRP nor limulin showed significant overall sequence homology to vertebrate immunoglobulins. However, CRP, limulin, and TEPC-15 variable region heavy chain (VH) shared short stretches of homology (8-10 amino acids) that mapped to a stretch comprised of the second complementarity determining region and third framework region of the TEPC-15 VH. These results might reflect either evolutionary convergence forced upon molecules of diverse evolutionary histories because of steric requirements of binding the same ligand, or a conservation of primitive combining site gene segments in evolution.

Animals↗

Development and spread of bacterial resistance to antimicrobial agents: an overview.

Resistance to antimicrobial agents is emerging in a wide variety of nosocomial and community-acquired pathogens. The emergence and spread of multiply resistant organisms represent the convergence of a variety of factors that include mutations in common resistance genes that extend their spectrum of activity, the exchange of genetic information among microorganisms, the evolution of selective pressures in hospitals and communities that facilitate the development and spread of resistant organisms, the proliferation and spread of multiply resistant clones of bacteria, and the inability of some laboratory testing methods to detect emerging resistance phenotypes. Twenty years ago, bacteria that were resistant to antimicrobial agents were easy to detect in the laboratory because the concentration of drug required to inhibit their growth was usually quite high and distinctly different from that of susceptible strains. Newer mechanisms of resistance, however, often result in much more subtle shifts in bacterial population distributions. Perhaps the most difficult phenotypes to detect, as shown in several proficiency testing surveys, are decreased susceptibility to beta-lactams in pneumococci and decreased susceptibility to vancomycin in staphylococci. In summary, emerging resistance has required adaptations and modifications of laboratory diagnostic techniques, empiric anti-infective therapy for such diseases as bacterial meningitis, and infection control measures in health care facilities of all kinds. Judicious use is imperative if we are to preserve our arsenal of antimicrobial agents into the next decade.

Anti-Bacterial Agents↗

Evolutionary reconstruction of networks.

Can a graph specifying the pattern of connections of a dynamical network be reconstructed from statistical properties of a signal generated by such a system? In this model study, we present a Metropolis algorithm for reconstruction of graphs from their Laplacian spectra. Through a stochastic process of mutations and selection, evolving test networks converge to a reference graph. Applying the method to several examples of random graphs, clustered graphs, and small-world networks, we show that the proposed stochastic evolution allows exact reconstruction of relatively small networks and yields good approximations in the case of large sizes.

Journal Article↗

Acoustical wave propagator

In this paper, an explicit acoustical wave propagator (AWP) is introduced to describe the time-domain evolution of acoustical waves. To implement its operation on an initial state of wave motion, the acoustical wave propagator is approximated as a Chebyshev polynomial expansion, which converges to machine accuracy. The spatial gradient in each polynomial term is evaluated by a Fourier transformation scheme. Analysis and numerical examples demonstrated that this Chebyshev-Fourier scheme is highly accurate and computational effective in predicting time-domain acoustical wave propagation and scattering.

Journal Article↗

Plasticity of enzyme active sites.

The expectation is that any similarity in reaction chemistry shared by enzyme homologues is mediated by common functional groups conserved through evolution. However, detailed enzyme studies have revealed the flexibility of many active sites, in that different functional groups, unconserved with respect to position in the primary sequence, mediate the same mechanistic role. Nevertheless, the catalytic atoms might be spatially equivalent. More rarely, the active sites have completely different locations in the protein scaffold. This variability could result from: (1) the hopping of functional groups from one position to another to optimize catalysis; (2) the independent specialization of a low-activity primordial enzyme in different phylogenetic lineages; (3) functional convergence after evolutionary divergence; or (4) circular permutation events.

Amino Acid Sequence↗

Evolution of structural shape in bacterial globin-related proteins.

The globin family of proteins has a characteristic structural pattern of helix interactions that nonetheless exhibits some variation. A simplified model for globin structural evolution was developed in which protein shape evolved by random change of contacts between helices. A conserved globin domain of 15 bacterial proteins representing four structural families was studied. Using a parsimony approach ancestral structural states could be reconstructed. The distribution of number of contact changes per site for a fixed topology tree fit a gamma distribution. Homoplasy was high, with multiple changes per site and no support for an invariant class of residue-residue contacts. Contacts changed more slowly than sequence. A phylogenetic reconstruction using a distance measure based on the proportion of shared contacts was generally consistent with a sequence-based phylogeny but not highly resolved. Contact pattern convergence between members of different globin family proteins could not be detected. Simulation studies indicated the convergence test was sensitive enough to have detected convergence involving only 10% of the contacts, suggesting a limit on the extent of selection for a specific contact pattern. Contact site methods may provide additional approaches to study the relationship between protein structure and sequence evolution.

Amino Acids↗

The evolution of begging: signaling and sibling competition.

In many species, young solicit food from their parents, which respond by feeding them. Because of the difference in genetic make-up between parents and their offspring and the consequent conflict, this interaction is often studied as a paradigm for the evolution of communication. Existent theoretical models demonstrate that chick signaling and parent responding can be stable if solicitation is a costly signal. The marginal cost of producing stronger signals allows the system to converge to an equilibrium: young beg with intensity that reflects their need, and parents use this information to maximize their own inclusive fitness. However, we show that there is another equilibrium where chicks do not beg and parents' provisioning effort is optimal with respect to the statistically probable distribution of chicks' states. Expected fitness for parents and offspring at the nonsignaling equilibrium is higher than at the signaling equilibrium. Because nonsignaling is stable and it is likely to be the ancestral condition, we would like to know how natural systems evolved from nonsignaling to signaling. We suggest that begging may have evolved through direct sibling fighting before the establishment of a parental response, that is, that nonsignaling squabbling leads to signaling. In multiple-offspring broods, young following a condition-dependent strategy in the contest for resources provide information about their condition. Parents can use this information even though it is not an adaptation for communication, and evolution will lead the system to the signaling equilibrium. This interpretation implies that signaling evolved in multiple-offspring broods, but given that signaling is evolutionarily stable, it would also be favored in species which secondarily evolved single-chick broods.

Animal Communication↗

Episodic adaptive evolution of primate lysozymes.

Although the darwinian concept of adaptation was established nearly a century ago, it has been difficult to demonstrate rigorously that the amino-acid differences between homologous proteins from different species have adaptive significance. There are currently two major types of sequence tests for positive darwinian selection on proteins from different species: sequence convergence, and neutral rate violation (reviewed in ref. 1). Lysozymes from the stomachs of cows and langur monkeys, two mammalian species displaying fermentation in the foregut, are an example of amino-acid sequence convergence among homologous proteins. Here we combine tests of neutral rate violation with reconstruction of ancestral sequences to document an episode of positive selection on the lineage leading to the common ancestor of the foregut-fermenting colobine monkeys. This analysis also detected a previously unsuspected adaptive episode on the lineage leading to the common ancestor of the modern hominoid lysozymes. Both adaptive episodes were followed by episodes of negative selection. Thus this approach can detect adaptive and purifying episodes, and localize them to specific lineages during protein evolution.

Adaptation, Physiological↗

Inversions in evolution of man and closely related species.

By the comparative study of the karyotypes of many Primates, 35 inversions (25 peri- and 10 paracentric) having accumulated during evolution of species related to man were reconstructed. Some of them originated human chromosomes from more ancestral chromosomes still present in other primate species. Their detection in man would indicate the occurrence of reverse mutations. Other inversions occurred in ancestral chromosomes identical to those of man, and originated chromosomes of other Primates species. Their detection in man would indicate the occurrence of a convergent mutation. It is shown that such reverse and convergent mutations do occur. They are too frequently observed than by mere chance among patients ascertained in human cytogenetic laboratories. Their excess is still larger among radiation induced inversions in human cells. This demonstrates the nonrandom occurrence of inversions. In addition, it is concluded that inversions which have accumulated during evolution are more representative of mutagenesis than those detected in human cytogenetic laboratories.

Animals↗

Evolution of migration under kin selection and local adaptation.

We present here a stochastic two-locus, two-habitat model for the evolution of migration with local adaptation and kin selection. One locus determines the migration rate while the other causes local adaptation. We show that the opposing forces of kin competition and local adaptation can lead to the existence of one or two convergence stable migration rates, notably depending on the recombination rate between the two loci. We show that linkage between migration and local adaptation loci has two antagonist effects: when linkage is tight, cost of local adaptation increases, leading to smaller equilibrium migration rates. However, when linkage is tighter, the population structure at the migration locus tends to be very high because of the indirect selection, and thus equilibrium migration rates increases. This result, qualitatively different from results obtained with other models of migration evolution, indicates that ignoring drift or the detail of the genetic architecture may lead to incorrect conclusions.

Adaptation, Biological↗

Modeling DNA structures: molecular mechanics and molecular dynamics.

Model building studies may be used to supplement structurally low resolution experimental data with detailed three-dimensional hypothetical atomic models. Because of the strong relation between structure and function in biological molecules such models may give a consistent, integral view of a wealth of experimental data. In most cases such models will predict the outcome of certain experiments. The outcome of these experiments will often either confirm the model may be used for further refinement or even demand a major revision of the model. Coordinates obtained from X-ray fiber diffraction data or in special cases single-crystal data may provide the elements for DNA or RNA model building. Local and nonlocal optimization may be used to refine these structures and to evaluate their statistical significance as estimated by a chosen force field. Appreciable progress using nonlocal optimization procedures can only be expected if the dimensionality of the problem can be reduced sufficiently to the relevant degrees of freedom. Taking advantage of structural symmetries may critically improve the convergence while refining the target molecule or its building blocks. Monte Carlo and molecular dynamics methods allow one to calculate averaged quantities. In addition, molecular dynamics provides time evolutions of certain averages. During the simulation of certain physical properties of molecules a huge amount of data will be generated. They will provide many answers, but these answers may not always apply to the original question. So what type of questions will be reliably answered by a force field? Relatively safe answers concern the local geometry of the molecules. If a conformation leads to strong distortions of bond distances or angles or to close van der Waals contacts, this conformation can safely be rejected. Optimizing such unfavorable structures energetically may lead to structures showing how to avoid such distortions. More difficult are energetical questions: which of two conformers is more stable, or what is the free energy of the substrate in the active site? One cannot always be sure that the force field provides the correct answer. Therefore, one should pose only those questions which can be checked experimentally. Because of the many possible answers, the experiment may benefit by starting with a choice proposed by the simulation. The application of this procedure to curved DNA and the DNA four-way junction was successful.

Base Sequence↗

Schistosomiasis: forty years' war on the worm.

Schistosome vaccine candidates are now entering phase I clinical trials. In an attempt to illustrate the progress made towards control, and the definition of potential vaccines against schistosomiasis, André Capron reviews some of the major findings and observations that have led to a significant evolution of our concepts, together with the production of novel and promising tools. It is obvious that our most important advances have proceeded from the successful integration of convergent knowledge in biology, epidemiology and biotechnology. At this stage, nobody can predict what will be the outcome of the current trials, but an important step has certainly been made towards immunointervention in human schistosomiasis.

Journal Article↗

[The French and English health systems: compared evolution after the mid-1990s].

In the recent past, the British and French health care systems have both undergone significant reforms, enveloped in a state of Urgency, resulting primarily in France from the increasing rate of growth in health expenditure and in England from malfunctioning procedures such as waiting lists. After describing current features of the National Health Service (NHS), this study extracts and considers the points of convergence and divergence in the respective policies of the two countries: similarities in the choice of priorities, decentralisation of decision-making, negotiation between actors at the local level, development of the quality concept, and the differences in formulating objectives and involving the system's users. The considerations provided here should allow for a better understanding of the developments of these respective health policies and their future evolution.

Delivery of Health Care↗

Evolution of ciliary patterns in the Oligotrichida (Ciliophora, Spirotricha) and its taxonomic implications.

Although the somatic ciliature of the Oligotrichida typically comprises only a girdle and ventral kinety, a considerable diversity of ciliary patterns occurs. The four main girdle kinety patterns are identically found in tailed and tail-less species. The contractile tail has a complicated and unique ultrastructure and is potentially useful for the cell's movement and/or stabilization during feeding. Accordingly, I assume that this structure has evolved only once, namely, in the Tontoniidae nov. fam., and that the different girdle kinety patterns developed convergently in the tailed and tail-less taxa. Further distinct features suggest the establishment of the families Cyrtostrombidiidae nov. fam. (with cyrtos-like pharyngeal fibres and lack of ventral membranelles and endoral) and Pelagostrombidiidae nov. fam. (with neoformation organelle). An attempt is made to reconstruct the evolution of the kinety patterns based on morphologic, ontogenetic, and ultrastructural data. Some genera of tail-less Oligotrichida base on differences in the ciliary pattern; Omegastrombidium nov. gen. is erected for a further girdle kinety pattern. Likewise, the tailed genus Tontonia is split, resulting in two new genera, viz., Pseudotontonia nov. gen. and Spirotontonia nov. gen. Furthermore, the genus Spirostrombidium is split due to the different origin of the parallel course of girdle and ventral kinety, and Parallelostrombidium nov. gen. is established. However, the genus Thigmostrombidium is rejected because its enlarged thigmotactic membranelles are interpreted as an adaptation to the benthic lifestyle, which occurred several times within different girdle kinety patterns.

Journal Article↗

Stomach lysozyme gene of the langur monkey: tests for convergence and positive selection.

Genomic blotting and enzymatic amplification show that the genome of the langur monkey (like that of other primates) contains only a single gene for lysozyme c, in contrast to another group of foregut fermenters, the ruminants, which have a multigene family encoding this protein. Therefore, the langur stomach lysozyme gene has probably evolved recently (i.e., within the period of monkey evolution) from a conventional primate lysozyme. The sequences of cDNAs for the stomach lysozyme of langur and the conventional lysozymes of three other Old World monkeys were determined. Identification of the promoter for the stomach gene and comparison to the human gene, which is expressed conventionally in macrophages, show that both lysozyme genes use the same promoter. This suggests that the difference in expression patterns is due to change(s) in enhancer or silencer regulatory elements. With the cDNA sequences the hypothesis that the langur stomach lysozyme has converged in amino acid sequence upon the stomach lysozymes of ruminants is tested. Consistent with the convergence hypothesis, only those sites that specify amino acids in the mature lysozyme are shared uniquely with ruminant lysozyme genes. None of the silent sites at third positions of codons or in noncoding regions support a link between the langur and ruminants. Statistical analysis based on silent sites rules out the possibility of horizontal transfer of a stomach lysozyme gene between the langur and ruminant lineages and supports the close relationship of the langur lysozyme gene to that of other monkeys.

Animals↗

Chromosomal sex-determining regions in animals, plants and fungi.

The independent evolution of sex chromosomes in many eukaryotic species raises questions about the evolutionary forces that drive their formation. Recent advances in our understanding of these genomic structures in mammals in parallel with alternate models such as the monotremes, fish, dioecious plants, and fungi support the idea of a remarkable convergence in structure to form large, non-recombining regions with discrete evolutionary strata. The discovery that evolutionary events similar to those that have transpired in humans have also occurred during the formation of sex chromosomes in organisms as divergent as the plant Silene, the fungus Cryptococcus and the fish medaka highlights the importance of future studies in these systems. Such investigation will broaden our knowledge of the evolution and plasticity of these ubiquitous genomic features underlying sexual dimorphism and reproduction.

Animals↗

Inference of Cytochrome P450 Evolutionary History Using Structural and Physicochemical Metrics.

Cytochrome P450s are a superfamily of heme-binding monooxygenases involved with the detoxification of intrinsic and extrinsic toxins. They are near ubiquitous within biological domains and are found in all domains. Members of families within the superfamily are defined based on amino acid identity thresholds, with thresholds as low as 40% in some families. Relationships among Cytochrome P450 families have proven elusive due to sub-Twilight Zone interfamily identities (<30%) that result in poor multiple sequence alignment quality and thus low levels of support for downstream phylogenetic reconstructions. Despite the low identities, Cytochrome P450 structures are remarkably well conserved both within and among families. In such cases, structural phylogenetics has the potential to unveil elusive relationships because the selectively favored physicochemical properties giving rise to the structure and function of the proteins persist despite sequence-level divergence. Recently, in two separate publications, we demonstrated that by utilizing physicochemical vectors, dynamic time warping, and hierarchical clustering (PCDTW), large swaths of protein domain families and betacoronavirus receptor-binding domain clades were congruent with validated functional/structural relationships. These were important findings because anomalous sequence alignment-based maximum likelihood phylogenetic findings, which were not congruent with the known functional relationships, were resolved. That also validated the use of physicochemical vectors in making inferences about structural/functional homology. Additionally, it illuminated that the same methods might be applied to other protein families with relationships that are difficult to resolve from sequence data alone. Herein, we used Molecular Weight and Hydrophobicity Physicochemical Dynamic Time Warping (MWHP PCDTW) along with structural and sequence alignment-based phylogenetic methodologies to analyze all of the Cytochrome P450s found both in the high-fidelity Structural Classificaction of Proteins (SCOP) database and the reviewed sequences with both experimentally resolved and de novo predicted structures in the Protein Data Bank and the AlphaFold (AF) Protein Structure Database, respectively. We compared the resulting phylogenetic topologies and found that in some cases, structure-based methods may be less able to resolve random/convergent similarity than physicochemical and sequence-based methodologies. This finding agrees with previous findings that demonstrate the usefulness of physicochemical properties in resolving both random structural similarity and potentially convergent relationships.

Cytochrome P-450 Enzyme System↗

Does interspecific hybridization influence evolutionary rates? An experimental study of laboratory adaptation in hybrids between Drosophila serrata and Drosophila birchii.

The low initial fitness of progeny from interspecific crosses in animals and the rarity of interspecific hybridization in natural environments have led to a debate about the evolutionary importance of this phenomenon. Here we directly assess the effects of hybridization between Drosophila serrata and Drosophila birchii on evolutionary rates. We looked at the effects on laboratory adaptation over 30 generations in two laboratory environments, one of which involved nutrition and temperature stress. Laboratory adaptation occurred over time in both environments as reflected by a marked change in viability. However, whilst hybrid lines at no stage performed poorly relative to parental lines, their rate of adaptation never exceeded that of the parentals. Thus, there was no evidence that hybridization increased evolutionary rates. Instead, hybrid lines converged phenotypically with one of the parental species.

Analysis of Variance↗