GPCR signalling to the translation machinery

G protein-coupled receptors (GPCRs) are involved in most physiological processes, many of them being engaged in fully differentiated cells. These receptors couple to transducers of their own, primarily G proteins and β-arrestins, which launch intracellular signalling cascades. Some of these signalling events regulate the translational machinery to fine-tune general cell metabolism or to alter protein expression pattern. Though extensively documented for tyrosine kinase receptors, translational regulation by GPCRs is still poorly appreciated. The objective of this review paper is to address the following questions: i) is there a “GPCR signature” impacting on the translational machinery, and ultimately on the type of mRNA translated? ii) are the regulatory networks involved similar as those utilized by tyrosine kinase receptors? In particular, we will discuss the specific features of translational control mediated by GPCRs and highlight the intrinsic properties of GPCRs these mechanisms could rely on.     

Regulation of GTPases in the bacterial translation machinery

Several GTPases participate in bacterial protein biosynthesis. Initiation factor 2 controls the formation of the ribosomal initiation complex and places initiator fMet-tRNAfMet in the ribosomal P-site. Elongation factors Tu and G are responsible for codon-specific binding of the aminoacyl-tRNA to the A-site, and peptidyl-tRNA to the P-site, respectively, during the elongation phase of protein biosynthesis. Release factor 3, a GTPase which is not ubiquitous, is involved in termination and release of the nascent polypeptide. Other translation factors, including initiation factors 1 and 3, elongation factor Ts, release factors 1 and 2, and ribosomal release factor do not belong to the family of GTP/GDP binding proteins. The guanosine nucleotide binding domains of the GTPases involved in translation are structurally related to the Galpha subunit of heterotrimeric G proteins and to the proteins of the Ras family. We have identified and sequenced all genes coding for translation factors in the extreme thermophile Thermus thermophilus. The proteins were overproduced in Escherichia coli, purified, biochemically characterised and used for crystallisation and structural analysis. Further biochemical investigations were aimed at gaining insight into the molecular mechanism underlying the regulation of the GTPase activity of the translation factors, and to elucidate the role of their ribosomal binding sites in this process.     

Origins and evolution of biological novelty

Understanding the origins and impacts of novel traits has been a perennial interest in many realms of ecology and evolutionary biology. Here, we build on previous evolutionary and philosophical treatments of this subject to encompass novelties across biological scales and eco-evolutionary perspectives. By defining novelties as new features at one biological scale that have emergent effects at other biological scales, we incorporate many forms of novelty that have previously been treated in isolation (such as novelty from genetic mutations, new developmental pathways, new morphological features, and new species). Our perspective is based on the fundamental idea that the emergence of a novelty, at any biological scale, depends on its environmental and genetic context. Through this lens, we outline a broad array of generative mechanisms underlying novelty and highlight how genomic tools are transforming our understanding of the origins of novelty. Lastly, we present several case studies to illustrate how novelties across biological scales and systems can be understood based on common mechanisms of change and their environmental and genetic contexts. Specifically, we highlight how gene duplication contributes to the evolution of new complex structures in visual systems; how genetic exchange in symbiosis alters functions of both host and symbiont, resulting in a novel organism; and how hybridisation between species can generate new species with new niches.     

Genome: Origins and evolution of the term

The appearance of a new scientific term is a significant event in the human cognitive process and the result of the realization of the separateness of an object or a phenomenon. Our article concentrates on the origins of basic genetic terms, such as genetics, gene, genotype, genome, gene pool, and genomics. We propose using the term karyogenomics for the special direction of genomics related to the study of the organization and evolution of eukaryotic genomes by means of modern chromosome analysis, as well as by full genome sequencing.     

Origin and evolution of the chloroplast division machinery

Chloroplasts were originally established in eukaryotes by the endosymbiosis of a cyanobacterium; they then spread through diversification of the eukaryotic hosts and subsequent engulfment of eukaryotic algae by previously nonphotosynthetic eukaryotes. The continuity of chloroplasts is maintained by division of preexisting chloroplasts. Like their ancestors, chloroplasts use a bacterial division system based on the FtsZ ring and some associated factors, all of which are now encoded in the host nuclear genome. The majority of bacterial division factors are absent from chloroplasts and several new factors have been added by the eukaryotic host. For example, the ftsZ gene has been duplicated and modified, plastid-dividing (PD) rings were most likely added by the eukaryotic host, and a member of the dynamin family of proteins evolved to regulate chloroplast division. The identification of several additional proteins involved in the division process, along with data from diverse lineages of organisms, our current knowledge of mitochondrial division, and the mining of genomic sequence data have enabled us to begin to understand the universality and evolution of the division system. The principal features of the chloroplast division system thus far identified are conserved across several lineages, including those with secondary chloroplasts, and may reflect primeval features of mitochondrial division. Shin-ya Miyagishima is the recipient of the Botanical Society Award for Young Scientists, 2004.     

Origins of translation: the hypothesis of permanently attached adaptors

A mechanism for prebiotic translation is proposed in which primeval transfer-RNA (adaptors) are assumed to be permanently associated with messenger nucleic acid molecules. Residual 'fossil' evidences are found to be present within the base sequences of contemporary tRNAs, suggesting the existence of inter-primal-tRNA interactions necessary for the mechanism. The structure of proposed primal-tRNA is such that it can not only choose its own amino acid in the absence of aminoacyl synthetase, but can also associate nonspecifically with adjacent primal-tRNA molecules attached to the neighbouring codons. Such associations can give rise, through cooperative binding between message and adaptors to the 'static template surfaces' which can direct translation of nucleotide sequences into those of amino acids. The origins of ribosomes and contemporary genetic code are suggested by this hypothesis. Proposed structures and processes are thermodynamically compatible. The approximate date of occurrence of the proposed system is calculated, which is consistent with the period of occurrence of the earliest organism with ribosomes.     

Origins and evolution of eukaryotic RNA interference

Small interfering RNAs (siRNAs) and genome-encoded microRNAs (miRNAs) silence genes via complementary interactions with mRNAs. With thousands of miRNA genes identified and genome sequences of diverse eukaryotes available for comparison, the opportunity emerges for insights into the origin and evolution of RNA interference (RNAi). The miRNA repertoires of plants and animals appear to have evolved independently. However, conservation of the key proteins involved in RNAi suggests that the last common ancestor of modern eukaryotes possessed siRNA-based mechanisms. Prokaryotes have an RNAi-like defense system that is functionally analogous but not homologous to eukaryotic RNAi. The protein machinery of eukaryotic RNAi seems to have been pieced together from ancestral archaeal, bacterial and phage proteins that are involved in DNA repair and RNA processing.     

Deuterium and its role in the machinery of evolution

An argument is presented that the spontaneous mutation rate, the core of evolution theory, may be dictated by the deuterium/hydrogen (D/H) abundance ratio. This argument is supported by quantum mechanical calculations of the zero-point energy reduction for DNA base pairs upon deuterium substitution for hydrogen and recent experiments that show that the rate of catalytic dsDNA unwinding is dependent on the stability of the dsDNA.     

Stepwise evolution of the Sec machinery in Proteobacteria

The Sec machinery facilitates the translocation of proteins across and into biological membranes. In several of the Proteobacteria, this machinery contains accessory features that are not present in any other bacterial division. The genomic distribution of these features in the context of bacterial phylogeny suggests that the Sec machinery has evolved in discrete steps. The canonical Sec machinery was initially supplemented with SecB; subsequently, SecE was extended with two transmembrane segments and, finally, SecM was introduced. The Sec machinery of Escherichia coli and other Enterobacteriales represents the end product of this stepwise evolution.     

Origins and evolution of AIDS viruses: estimating the time-scale

The primate lentiviruses comprise SIV strains from various host species, as well as two viruses, HIV-1 and HIV-2, that cause AIDS in humans. The origins of HIV-1 and HIV-2 have been traced to cross-species transmissions from chimpanzees and sooty mangabey monkeys respectively. Two approaches have been taken to estimate the time-scale of the evolution of these viruses. Certain groups of SIV strains appear to have evolved in a host-dependent manner, implying a time-scale of many thousands or even millions of years. In stark contrast, molecular clock calculations have previously been used to estimate a time-scale of only tens or hundreds of years. Those calculations largely ignored heterogeneity of evolutionary rates across different sites within sequences. In fact, the distribution of rates at different sites seems extremely skewed in HIV-1, and so the time-depth of the primate lentivirus evolutionary tree may have been underestimated by at least a factor of ten. However, these date estimates still seem to be far too recent to be consistent with host-dependent evolution.     

Origins and early evolution of herbivory in tetrapods

The first herbivorous tetrapods date from the Late Carboniferous, about 300 million years ago. By the Late Permian, continental ecosystems of `modern' aspect had been established, with a vast standing crop of herbivores supporting relatively few carnivores. Processing of high-fibre plant material requires (1) structural modifications of the dentition, jaw apparatus and digestive tract and (2) the acquisition of microbial endosymbionts that produce the enzymes needed for fermentative digestion of cellulose, the principal compound of cell walls in plants. Recent phylogenetic analyses of tetrapods indicate that endosymbiotic cellulysis was acquired independently in a number of lineages during the late Palaeozoic.