The evolutionary analysis reveals domain fusion of proteins with Frizzled-like CRD domain

Frizzleds (FZDs) are transmembrane receptors in the Wnt signaling pathway and they play pivotal roles in developments. The Frizzled-like extracellular Cysteine-rich domain (Fz-CRD) has been identified in FZDs and other proteins. The origin and evolution of these proteins with Fz-CRD is the main interest of this study. We found that the Fz-CRD exists in FZD, SFRP, RTK, MFRP, CPZ, CORIN, COL18A1 and other proteins. Our systematic analysis revealed that the Fz-CRD domain might have originated in protists and then fused with the Frizzled-like seven-transmembrane domain (7TM) to form the FZD receptors, which duplicated and diversified into about 11 members in Vertebrates. The SFRPs and RTKs with the Fz-CRD were found in sponge and expanded in Vertebrates. Other proteins with Fz-CRD may have emerged during Vertebrate evolution through domain fusion. Moreover, we found a glycosylation site and several conserved motifs in FZDs, which may be related to Wnt interaction. Based on these results, we proposed a model showing that the domain fusion and expansion of Fz-CRD genes occurred in Metazoa and Vertebrates. Our study may help to pave the way for further research on the conservation and diversification of Wnt signaling functions during evolution.     

The dynamics and evolutionary potential of domain loss and emergence

The wealth of available genomic data presents an unrivaled opportunity to study the molecular basis of evolution. Studies on gene family expansions and site-dependent analyses have already helped establish important insights into how proteins facilitate adaptation. However, efforts to conduct full-scale cross-genomic comparisons between species are challenged by both growing amounts of data and the inherent difficulty in accurately inferring homology between deeply rooted species. Proteins, in comparison, evolve by means of domain rearrangements, a process more amenable to study given the strength of profile-based homology inference and the lower rates with which rearrangements occur. However, adapting to a constantly changing environment can require molecular modulations beyond reach of rearrangement alone. Here, we explore rates and functional implications of novel domain emergence in contrast to domain gain and loss in 20 arthropod species of the pancrustacean clade. Emerging domains are more likely disordered in structure and spread more rapidly within their genomes than established domains. Furthermore, although domain turnover occurs at lower rates than gene family turnover, we find strong evidence that the emergence of novel domains is foremost associated with environmental adaptation such as abiotic stress response. The results presented here illustrate the simplicity with which domain-based analyses can unravel key players of nature's adaptational machinery, complementing the classical site-based analyses of adaptation.     

The evolutionary relationship of the domain architectures in the RhoGEF-containing proteins

Domain insertions and deletions lead to variations in the domain architectures of the proteins from their common ancestor. In this work, we investigated four groups of the RhoGEF-containing proteins from different organisms with domain architectures RhoGEF-PH-SH3, SH3-RhoGEF-PH, RhoGEF-PH, and SH3-RhoGEF defined in the Pfam database. The phylogenetic trees were constructed using each individual domain and/or the combinations of all the domains. The phylogenetic analysis suggests that RhoGEF-PH-SH3 and SH3-RhoGEF-PH might have evolved from RhoGEF-PH through the insertion of SH3 independently, while SH3- RhoGEF of proteins in fruit fly might have evolved from SH3-RhoGEF-PH by the degeneration of PH domain.     

The critical dimensions of the response-reinforcer contingency

Two major dimensions of any contingency of reinforcement are the temporal relation between a response and its reinforcer, and the relative frequency of the reinforcer given the response versus when the response has not occurred. Previous data demonstrate that time, per se, is not sufficient to explain the effects of delay-of-reinforcement procedures; needed in addition is some account of the events occurring in the delay interval. Moreover, the effects of the same absolute time values vary greatly across situations, such that any notion of a standard delay-of-reinforcement gradient is simplistic. The effects of reinforcers occurring in the absence of a response depend critically upon the stimulus conditions paired with those reinforcers, in much the same manner as has been shown with Pavlovian contingency effects. However, it is unclear whether the underlying basis of such effects is response competition or changes in the calculus of causation.     

Comprehensive analysis of all evolutionary paths between two divergent PDZ domain specificities

To understand the molecular evolution of functional diversity in protein families, we comprehensively investigated the consequences of all possible mutation combinations separating two peptide‐binding domains with highly divergent specificities. We analyzed the Erbin PDZ domain (Erbin‐PDZ), which exhibits canonical type I specificity, and a synthetic Erbin‐PDZ variant (E‐14) that differs at six positions and exhibits an atypical specificity that closely resembles that of the natural Pdlim4 PDZ domain (Pdlim4‐PDZ). We constructed a panel of 64 PDZ domains covering all possible transitions between Erbin‐PDZ and E‐14 (i.e., the panel contained variants with all possible combinations of either the Erbin‐PDZ or E‐14 sequence at the six differing positions). We assessed the specificity profiles of the 64 PDZ domains using a C‐terminal phage‐displayed peptide library containing all possible genetically encoded heptapeptides. The specificity profiles clustered into six distinct groups, showing that intermediate domains can be nodes for the evolution of divergent functions. Remarkably, three substitutions were sufficient to convert the specificity of Erbin‐PDZ to that of Pdlim4‐PDZ, whereas Pdlim4‐PDZ contains 71 differences relative to Erbin‐PDZ. X‐ray crystallography revealed the structural basis for specificity transition: a single substitution in the center of the binding site, supported by contributions from auxiliary substitutions, altered the main chain conformation of the peptide ligand to resemble that of ligands bound to Pdlim4‐PDZ. Our results show that a very small set of mutations can dramatically alter protein specificity, and these findings support the hypothesis whereby complex protein functions evolve by gene duplication followed by cumulative mutations.     

The social contingency model and olive baboons

A theoretical and illustrative analysis of sequences of actions between pairs of olive baboons (Papio cynocephals anubis) is carried out using the social contingency model originally suggested by Jones and Gerard (1967) in social psychology. The model provides the basis for a step-by-step analysis and a typology. Signals from body postures, facial expressions, and vocalizations are subject to close study by using the model, in a similar fashion to its use in social skills analysis (Argyle, 1988). Sequences are categorized according to individual and joint strategies. Examples are given of three categories of contingency, reactive, mutual, and asymmetrical, which are adapted from their social psychological usage. The model is extended by a new category for competitive relationships between baboons: a conflictive category. The contingencies, as they are shown graphically, have a superficial resemblance to Tinbergen's (1951) zigzag diagrams, but their purpose is distinct in focusing on the detail of both infrequent and repeated interactions. The overall aim of the contingencies is to improve the analysis of social behavior at the proximate level and the model is potentially applicable to observation records at a level of detail that is often not utilized in reporting field studies.     

Structure, function and evolutionary relationship of proteins containing a disintegrin domain.

Disintegrins are soluble integrin ligands from snake venoms that disrupt cell-matrix interactions. Recently, the nuclear magnetic resonance structures of two disintegrins were determined, providing provocative molecular insight into how a disintegrin may engage an integrin. In addition, it has recently been realized that disintegrins are derived from larger multifunctional proteins, and that there is a family of membrane-anchored, disintegrin domain-containing proteins that may promote important cell-cell interactions.     

Comparative transcriptional profiling and evolutionary analysis of the GRAM domain family in eukaryotes

The GRAM domain was found in glucosyltransferases, myotubularins and other membrane-associated proteins. So far, functions for majority of these proteins are yet to be uncovered. In order to address the evolutionary and functional significance of this family members, we have performed a comprehensive investigation on their genome-wide identification, phylogenetic relationship and expression divergence in five different organisms representing monocot/dicot plants, vertebrate/invertebrate animals and yeast, namely, Oryza sativa, Arabidopsis thaliana, Mus musculus, Drosophila melanogaster and Saccharomyces cerevisiae, respectively. We have identified 65 members of GRAM domain family from these organisms. Our data revealed that this family was an ancient group and various organisms had evolved into different family sizes. Large-scale genome duplication and divergence in both expression patterns and functions were significantly contributed to the expansion and retention of this family. Mouse and Drosophila members showed higher divergences in their proteins as indicated by higher Ka/Ks ratios and possessed multiple domains in various combinations. However, in plants, their protein functions were possibly retained with a relatively low divergence as signified by lower Ka/Ks ratios and only one additional domain was combined during evolution. On the other hand, this family in all five organisms exhibited high divergence in their expression patterns both at tissue level and under various biotic and abiotic stresses. These highly divergent expression patterns unraveled the complexity of functions of GRAM domain family. Each member may play specialized roles in a specific tissue or stress condition and may function as regulators of environmental and hormonal signaling.     

The analysis of stratified 2 x 2 contingency tables

We consider the problem of testing for independence against the consistent superiority of one treatment over another when the response variable is binary and is compared across two treatments in each of several strata. Specifically, we consider the randomized clinical trial setting. A number of issues arise in this context. First, should tables be combined if there are small or zero margins? Second, should one assume a common odds ratio across strata? Third, if the odds ratios differ across strata, then how does the standard test (based on a common odds ratio) perform? Fourth, are there other analyzes that are more appropriate for handling a situation in which the odds ratios may differ across strata? In addressing these issues we find that the frequently used Cochran–Mantel–Haenszel test may have a poor power profile, despite being optimal when the odds ratios are common. We develop novel tests that are analogous to the Smirnov, modified Smirnov, convex hull, and adaptive tests that have been proposed for ordered categorical data. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Behavioral contingency analysis

This paper presents a formal symbolic language, with its own specialized vocabulary and grammar, for codifying any behavioral contingency, including the complex multiparty contingencies encountered in law, economics, business, public affairs, sociology, education, and psychotherapy. This language specifies the "if, then" and temporal relationships between acts and their consequences for the parties involved. It provides for the notation of the probabilities, magnitudes, positive or negative valences, or time delays of the consequences for the parties, and for the parties that would perceive, misperceive, not perceive, predict, mispredict, or not predict events. The language's fractal-like hierarchical and recursive grammar provides for the flexible combination and permutation of the modifiers of the language's four nouns: acts, consequences, time intervals, and agents of acts; and its four verbs: consequate, prevent, perceive, and predict-thereby giving the language the ability to describe and codify various nuances of such complex contingencies as fraud, betting, blackmail, various types of games, theft, crime and punishment, contracts, family dynamics, racing, competition, mutual deterrence, feuding, bargaining, deception, borrowing, insurance, elections, global warming, tipping for service, vigilance, sexual overtures, decision making, and mistaken identity. Applications to the management of practical situations and techniques for doing so, as well as applications in current behavior analysis research and neuroscience, are discussed.     

Structure of the EMAPII domain of human aminoacyl-tRNA synthetase complex reveals evolutionary dimer mimicry

The EMAPII (endothelial monocyte-activating polypeptide II) domain is a tRNA-binding domain associated with several aminoacyl-tRNA synthetases, which becomes an independent domain with inflammatory cytokine activity upon apoptotic cleavage from the p43 component of the multisynthetase complex. It comprises a domain that is highly homologous to bacterial tRNA-binding proteins (Trbp), followed by an extra domain without homology to known proteins. Trbps, which may represent ancient tRNA chaperones, form dimers and bind one tRNA per dimer. In contrast, EMAPII domains are monomers. Here we report the crystal structure at 1.14 Angstroms of human EMAPII. The structure reveals that the Trbp-like domain, which forms an oligonucleotide-binding (OB) fold, is related by degenerate 2-fold symmetry to the extra-domain. The pseudo-axis coincides with the dyad axis of bacterial TtCsaA, a Trbp whose structure was solved recently. The interdomain interface in EMAPII mimics the intersubunit interface in TtCsaA, and may thus generate a novel OB-fold-based tRNA-binding site. The low sequence homology between the extra domain of EMAPII and either its own OB fold or that of Trbps suggests that dimer mimicry originated from convergent evolution rather than gene duplication.