Evolutionary specialization of a tryptophan indole group for transition-state stabilization by eukaryotic transglutaminases

Covalent posttranslational protein modifications by eukaryotic transglutaminases proceed by a kinetic pathway of acylation and deacylation. Ammonia is released as the acylenzyme is formed, whereas the cross-linked product is released later in the deacylation step. Superposition of the active sites of transglutaminase type 2 (TG2) and the structurally related cysteine protease, papain, indicates that in the formation of tetrahedral intermediates, the backbone nitrogen of the catalytic Cys-277 and the N_Ɛ1 nitrogen of Trp-241 of TG2 could contribute to transition-state stabilization. The importance of this Trp-241 side chain was demonstrated by examining the kinetics of dansylcadaverine incorporation into a model peptide. Although substitution of the Trp-241 side chain with Ala or Gly had only a small effect on the Michaelis constant K_m (1.5-fold increase), it caused a >300-fold lowering of the catalytic rate constant k_cat. The wild-type and mutant TG2-catalyzed release of ammonia showed kinetics similar to the kinetics for the formation of cross-linked product, indicating that transitionstate stabilization in the acylation step was rate-limiting. In papain, a Gln residue is at the position of TG2-Trp-241. The conservation of Trp-241 in all eukaryotic transglutaminases and the finding that W241Q-TG2 had a much lower k_cat than wild-type enzyme suggest evolutionary specialization in the use of the indole group. This notion is further supported by the observation that transitionstate- stabilizing side chains of Tyr and His that operate in some serine and metalloproteases only partially substituted for Trp.

Emotion processing fails to modulate putative mirror neuron response to trained visuomotor associations

Recent neuroimaging studies have demonstrated that activation of the putative human mirror neuron system (MNS) can be elicited via visuomotor training. This is generally interpreted as supporting an associative learning account of the mirror neuron system (MNS) that argues against the ontogeny of the MNS to be an evolutionary adaptation for social cognition. The current study assessed whether a central component of social cognition, emotion processing, would influence the MNS activity to trained visuomotor associations, which could support a broader role of the MNS in social cognition. Using functional magnetic resonance imaging (fMRI), we assessed repetition suppression to the presentation of stimulus pairs involving a simple hand action and a geometric shape that was either congruent or incongruent with earlier association training. Each pair was preceded by an image of positive, negative, or neutral emotionality. In support of an associative learning account of the MNS, repetition suppression was greater for trained pairs compared with untrained pairs in several regions, primarily supplementary motor area (SMA) and right inferior frontal gyrus (rIFG). This response, however, was not modulated by the valence of the emotional images. These findings argue against a fundamental role of emotion processing in the mirror neuron response, and are inconsistent with theoretical accounts linking mirror neurons to social cognition.

Fine-scale adaptation in a clonal sea anemone

Local adaptation in response to fine-scale spatial heterogeneity is well documented in terrestrial ecosystems. In contrast, in marine environments local adaptation has rarely been documented or rigorously explored. This may reflect real or anticipated effects of genetic homogenization, resulting from widespread dispersal in the sea. However, evolutionary theory predicts that for the many benthic species with complex life histories that include both sexual and asexual phases, each parental habitat patch should become dominated by the fittest and most competitive clones. In this study we used genotypic mapping to show that within headlands, clones of the sea anemone Actinia tenebrosa show restricted distributions to specific habitats despite the potential for more widespread dispersal. On these same shores we used reciprocal transplant experiments that revealed strikingly better performance of clones within their natal rather than foreign habitats as judged by survivorship, asexual fecundity, and growth. These findings highlight the importance of selection for fine-scale environmental adaptation in marine taxa and imply that the genotypic structure of populations reflects extensive periods of interclonal competition and site-specific selection.

Fuzzy ARTMAP and hybrid evolutionary programming for pattern classification

In this paper, an Evolutionary Artificial Neural Network (EANN) that combines the Fuzzy ARTMAP (FAM) network and a Hybrid Evolutionary Programming (HEP) model is introduced. The proposed FAM-HEP model, which combines the strengths of FAM and HEP, is able to construct its network structure autonomously as well as to perform learning and evolutionary search and adaptation concurrently. The effectiveness of the proposed FAM-HEP network is assessed empirically using several benchmark data sets and a real medical diagnosis problem. The performance of FAM-HEP is analyzed, and the results are compared with those of FAM-EP, FAM, and other classification models. In general, the results of FAM-HEP are better than those of FAM-EP and FAM, and are comparable with those from other classification models. The study also reveals the potential of FAM-HEP as an innovative EANN model for undertaking pattern classification problems in general, and a promising computerized decision support tool for tackling medical diagnosis tasks in particular.

A call for an expanded synthesis of developmental and evolutionary paradigms

Charney's target article continues a critique of genetic blueprint models of development that suggests reconsideration of concepts of adaptation, inheritance, and environment, which can be well illustrated in current research on infant attachment. The concepts of development and adaptation are so heavily based on the model of genetics and inheritance forged in the modern synthesis that they will require reconsideration to accommodate epigenetic inheritance.

Evolutionary perspective of cancer: myth, metaphors, and reality

The evolutionary perspective of cancer (which origins and dynamics result from evolutionary processes) has gained significant international recognition over the past decade and generated a wave of enthusiasm among researchers. In this context, several authors proposed that insights into evolutionary and adaptation dynamics of cancers can be gained by studying the evolutionary strategies of organisms. Although this reasoning is fundamentally correct, in our opinion, it contains a potential risk of excessive adaptationism, potentially leading to the suggestion of complex adaptations that are unlikely to evolve among cancerous cells. For example, the ability of recognizing related conspecifics and adjusting accordingly behaviors as in certain free-living species appears unlikely in cancer. Indeed, despite their rapid evolutionary rate, malignant cells are under selective pressures for their altered lifestyle for only few decades. In addition, even though cancer cells can theoretically display highly sophisticated adaptive responses, it would be crucial to determine the frequency of their occurrence in patients with cancer, before therapeutic applications can be considered. Scientists who try to explain oncogenesis will need in the future to critically evaluate the metaphorical comparison of selective processes affecting cancerous cells with those affecting organisms. This approach seems essential for the applications of evolutionary biology to understand the origin of cancers, with prophylactic and therapeutic applications.

Evolutionary biology of the invasive Northern Pacific seastar, Asterias amurensis

 Mark investigated the genetic basis of environmental adaptation in invasive and native A. amurensis larvae. He showed rapid changes in genetic architecture and gene expression underlie different physiological responses to elevated temperatures in invasive larvae. These findings are the first step in understanding the potential for range expansion within Australia.

What are we missing about marine invasions? Filling in the gaps with evolutionary genomics

Research on invasion biology has been largely dominated by studies on the ecological effects of invasion events, although recently, evolutionary processes have been shown to be important to invasion success. This is largely attributed to novel genomic tools that provide new opportunities to unravel the natural history, taxonomy, and invasion pathways of invasive species, as well as the genetic basis of adaptive traits that allow them to expand within and beyond their native range. Despite these advances and the growing literature of genomic research on terrestrial pests, these tools have not been widely applied to marine invasive species. This is in part due to the perception that high levels of dispersal and connectivity in many invasive marine species can limit the opportunity for local adaptation. However, there is growing evidence that even in species with high dispersal potential, significant site-specific adaptation can occur. We review how these “omic” tools provide unprecedented opportunities to characterise the role of adaptive variation, physiological tolerance, and epigenetic processes in determining the success of marine invaders. Yet, rapid range expansion in invasions can confound the analysis of genomic data, so we also review how data should be properly analysed and carefully interpreted under such circumstances. Although there are a limited number of studies pioneering this research in marine systems, this review highlights how future studies can be designed to integrate ecological and evolutionary information. Such datasets will be imperative for the effective management of marine pests.