Evolution Of Signaling Pathways Research Articles

A drug-resistant mutation in plant target of rapamycin validates the specificity of ATP-competitive TOR inhibitors in vivo.

Kinases are major components of cellular signaling pathways, regulating key cellular activities through phosphorylation. Kinase inhibitors are efficient tools for studying kinase targets and functions, however assessing their kinase specificity in vivo is essential. The identification of resistant kinase mutants has been proposed to be the most convincing approach to achieve this goal. Here, we address this issue in plants via a pharmacogenetic screen for mutants resistant to the ATP-competitive TOR inhibitor AZD-8055. The eukaryotic TOR (Target of Rapamycin) kinase is emerging as a major hub controlling growth responses in plants largely thanks to the use of ATP-competitive inhibitors. We identified a dominant mutation in the DFG motif of the Arabidopsis TOR kinase domain that leads to very strong resistance to AZD-8055. This resistance was characterized by measuring root growth, photosystem II (PSII) activity in leaves and phosphorylation of YAK1 (Yet Another Kinase 1) and RPS6 (Ribosomal protein S6), a direct and an indirect target of TOR respectively. Using other ATP-competitive TOR inhibitors, we also show that the dominant mutation is particularly efficient for resistance to drugs structurally related to AZD-8055. Altogether, this proof-of-concept study demonstrates that a pharmacogenetic screen in Arabidopsis can be used to successfully identify the target of a kinase inhibitor in vivo and therefore to demonstrate inhibitor specificity. Thanks to the conservation of kinase families in eukaryotes, and the possibility of creating amino acid substitutions by genome editing, this work has great potential for extending studies on the evolution of signaling pathways in eukaryotes.

Evolution of Regeneration in Animals: A Tangled Story

The evolution of regenerative capacity in multicellular animals represents one of the most complex and intriguing problems in biology. How could such a seemingly advantageous trait as self-repair become consistently attenuated by the evolution? This review article examines the concept of the origin and nature of regeneration, its connection with the processes of embryonic development and asexual reproduction, as well as with the mechanisms of tissue homeostasis. The article presents a variety of classical and modern hypotheses explaining different trends in the evolution of regenerative capacity which is not always beneficial for the individual and notably for the species. Mechanistically, these trends are driven by the evolution of signaling pathways and progressive restriction of differentiation plasticity with concomitant advances in adaptive immunity. Examples of phylogenetically enhanced regenerative capacity are considered as well, with appropriate evolutionary reasoning for the enhancement and discussion of its molecular mechanisms.

High variability of expression profiles of homeologous genes for Wnt, Hh, Notch, and Hippo signaling pathways in Xenopus laevis

Cell signaling pathways, such as Wnt, Hedgehog (Hh), Notch, and Hippo, are essential for embryogenesis, organogenesis, and tissue homeostasis. In this study, we analyzed 415 genes involved in these pathways in the allotetraploid frog, Xenopus laevis. Most genes are retained in two subgenomes called L and S (193 homeologous gene pairs and 29 singletons). This conservation rate of homeologs is much higher than that of all genes in the X. laevis genome (86.9% vs 60.2%). Among singletons, 24 genes are retained in the L subgenome, a rate similar to the average for all genes (82.8% vs 74.6%). In addition, as general components of signal transduction, we also analyzed 32 heparan sulfate proteoglycan (HSPG)-related genes and eight TLE/Groucho transcriptional corepressors-related genes. In these gene sets, all homeologous pairs have been retained. Transcriptome analysis using RNA-seq data from developmental stages and adult tissues demonstrated that most homeologous pairs of signaling components have variable expression patterns, in contrast to the conservative expression profiles of homeologs for transcription factors. Our results indicate that homeologous gene pairs for cell signaling regulation have tended to become subfunctionalized after allotetraploidization. Diversification of signaling pathways by subfunctionalization of homeologs may enhance environmental adaptability. These results provide insights into the evolution of signaling pathways after polyploidization.

Expanding the view on the evolution of the nematode dauer signalling pathways: refinement through gene gain and pathway co-option.

BackgroundSignalling pathways underlie development, behaviour and pathology. To understand patterns in the evolution of signalling pathways, we undertook a comprehensive investigation of the pathways that control the switch between growth and developmentally quiescent dauer in 24 species of nematodes spanning the phylum.ResultsOur analysis of 47 genes across these species indicates that the pathways and their interactions are not conserved throughout the Nematoda. For example, the TGF-β pathway was co-opted into dauer control relatively late in a lineage that led to the model species Caenorhabditis elegans. We show molecular adaptations described in C. elegans that are restricted to its genus or even just to the species. Similarly, our analyses both identify species where particular genes have been lost and situations where apparently incorrect orthologues have been identified.ConclusionsOur analysis also highlights the difficulties of working with genome sequences from non-model species as reliance on the published gene models would have significantly restricted our understanding of how signalling pathways evolve. Our approach therefore offers a robust standard operating procedure for genomic comparisons.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-2770-7) contains supplementary material, which is available to authorized users.

Plant Signalling Pathways: A Comparative Evolutionary Overview

It is an exciting time in the world of plant signal transduction research. Not only has the last few years seen major advances in our understanding of previously refractory topics, such as hormone receptors, but also the increased and indeed increasing availability of sequenced plant genomes provides an unprecedented opportunity to start asking questions about the evolution of signalling pathways. Recognizing that it would be timely to assess progress in these areas, in this issue of Current Biology we have drawn together a series of articles from leading figures in the field designed both to review recent advances and to begin to ask questions about the origin of signalling pathways in plants and their relationship to stimulus–response coupling in other organisms.

The evolution of signalling pathways in animal development.

Despite the bewildering number of cell types and patterns found in the animal kingdom, only a few signalling pathways are required to generate them. Most cell-cell interactions during embryonic development involve the Hedgehog, Wnt, transforming growth factor-beta, receptor tyrosine kinase, Notch, JAK/STAT and nuclear hormone pathways. Looking at how these pathways evolved might provide insights into how a few signalling pathways can generate so much cellular and morphological diversity during the development of individual organisms and the evolution of animal body plans.