Evolution of Pentameric Ligand-Gated Ion Channels: Pro-Loop Receptors

Pentameric ligand-gated ion channels (pLGICs) are ubiquitous neurotransmitter receptors in Bilateria, with a small number of known prokaryotic homologues. Here we describe a new inventory and phylogenetic analysis of pLGIC genes across all kingdoms of life. Our main finding is a set of pLGIC genes in unicellular eukaryotes, some of which are metazoan-like Cys-loop receptors, and others devoid of Cys-loop cysteines, like their prokaryotic relatives. A number of such “Cys-less” receptors also appears in invertebrate metazoans. Together, those findings draw a new distribution of pLGICs in eukaryotes. A broader distribution of prokaryotic channels also emerges, including a major new archaeal taxon, Thaumarchaeota. More generally, pLGICs now appear nearly ubiquitous in major taxonomic groups except multicellular plants and fungi. However, pLGICs are sparsely present in unicellular taxa, suggesting a high rate of gene loss and a non-essential character, contrasting with their essential role as synaptic receptors of the bilaterian nervous system. Multiple alignments of these highly divergent sequences reveal a small number of conserved residues clustered at the interface between the extracellular and transmembrane domains. Only the “Cys-loop” proline is absolutely conserved, suggesting the more fitting name “Pro loop” for that motif, and “Pro-loop receptors” for the superfamily. The infered molecular phylogeny shows a Cys-loop and a Cys-less clade in eukaryotes, both containing metazoans and unicellular members. This suggests new hypotheses on the evolutionary history of the superfamily, such as a possible origin of the Cys-loop cysteines in an ancient unicellular eukaryote. Deeper phylogenetic relationships remain uncertain, particularly around the split between bacteria, archaea, and eukaryotes.     

Habitat, Niche, and Evolution of Sirenian Mating Systems

Lek polygyny, monogamy and scramble promiscuity have been reported in the two families and five species of Recent sirenians. Evidence for lek mating in the dugong or "sea pig" (Dugong dugon), monogamy in Steller's sea cow (Hydrodamalis gigas), and scramble promiscuity in the three manatees or "river cows" (Trichechus manatus, Trichechus senegalensis, and Trichechus inunguis), as well as in one dugong population, is reviewed. Sirenians are long-lived "K-strategists" with precocious young, few potential young per female lifetime, high female investment in a few young, little apparent opportunity for post-copulatory male investment, and "paenungulate" reproductive physiologies that appear to increase uncertainty as to female receptivity and assurance as to paternity. Common features notwithstanding, diverse habitats, climates, and niches may account for mating system diversity. Scenarios for evolution of diverse mating systems, based on our understanding of mating systems in terrestrial herbivores, are presented. The dugong retains the ancestral low latitude marine, seagrass dependent, bottom-feeding, niche characteristic of diverse, tusked, Oligocene and Miocene sirenian faunas. With a long breeding season and high polygyny potential, retention of tusks by male dugongs in the absence of any foraging function suggests that tusks may have always had social functions and lekking may be of ancient origin. The sea cow lineage, isolated on the shoreline of the northeastern Pacific as seagrasses declined, turned to surface foraging on chemically undefended kelps and lost both tusks and molar teeth. As it followed kelps northwards, adaptation to a cold-temperate climate compressed the breeding season, limited the polygyny potential, and, in conjunction with incentives for paternal investment, favored pair bonding and the monogamous mating system postulated by George Steller (1751). Manatees, evolving in botanically-rich fresh waters of the Amazon basin as an aberrant offshoot of the marine dugongid line, remained in the tropics and retained a high polygyny potential, but became generalist foragers in the upper few meters of the water column. Labyrinthine river systems provided little opportunity for male aggregation and display (or rhizome foraging) and tusks were lost as the uncertainty of female inseminability drove the mating system toward scramble promiscuity and sperm competition. An observation of manatee-like behavior in a dense and sedentary dugong population in eastern Australia suggests plasticity in sirenian mating, and the likelihood that a form of scramble promiscuity may exist where no suitable site for lekking is available, where large group size makes female defence impossible, or where vulnerability of territorial males to hunting has resulted in extirpation of a lekking tradition. Dugong and manatee life history characteristics conform to expectations based on observed differences in mating systems.     

Evolution of the Cholecystokinin and Gastrin Peptides and Receptors

The intestinal hormone, cholecystokinin (CCK), and the stomachhormone, gastrin, form a simple two member family of peptideswith much to offer students of hormone and receptor evolution.They share a common carboxyl-terminal tetrapeptide sequence,which is the bioactive site of each peptide and is also antigenic,making heterologous biological and immunological assays feasible.Current evidence indicates that CCK evolved in chordate ancestorsand that gastrin-like peptides that separately regulate stomachfunctions evolved from an ancestral CCK at the level of thedivergence of tetrapods from fish. This tentative conclusionmay require modification when the two separate CCK- and gastrin-likepeptides recently identified in the dogfish shark are characterizedfurther. The CCK-X receptor appears to be ancestral to the CCK-Aand CCK-B receptors identified in amniotes. The evolution ofgastrin and of CCK-A and -B receptors may have played rolesin the evolution of the stomach and the evolution of endothermyin vertebrate phylogeny.     

Alpha-synuclein and Protein Degradation Systems: a Reciprocal Relationship

An increasing wealth of data indicates a close relationship between the presynaptic protein alpha-synuclein and Parkinson’s disease (PD) pathogenesis. Alpha-synuclein protein levels are considered as a major determinant of its neurotoxic potential, whereas secreted extracellular alpha-synuclein has emerged as an additional important factor in this regard. However, the manner of alpha-synuclein degradation in neurons remains contentious. Both the ubiquitin–proteasome system (UPS) and the autophagy–lysosome pathway (ALP)—mainly macroautophagy and chaperone-mediated autophagy—have been suggested to contribute to alpha-synuclein turnover. Additionally, other proteases such as calpains, neurosin, and metalloproteinases have been also proposed to have a role in intracellular and extracellular alpha-synuclein processing. Both UPS and ALP activity decline with aging and such decline may play a pivotal role in many neurodegenerative conditions. Alterations in these major proteolytic pathways may result in alpha-synuclein accumulation due to impaired clearance. Conversely, increased alpha-synuclein protein burden promotes the generation of aberrant species that may impair further UPS or ALP function, generating thus a bidirectional positive feedback loop leading to neuronal death. In the current review, we summarize the recent findings related to alpha-synuclein degradation, as well as to alpha-synuclein-mediated aberrant effects on protein degradation systems. Identifying the factors that regulate alpha-synuclein association to cellular proteolytic pathways may represent potential targets for therapeutic interventions in PD and related synucleinopathies.     

Structure,Function, and Evolution of Bacterial ATP-Binding Cassette Systems

Summary: ATP-binding cassette (ABC) systems are universally distributed among living organisms and function in many different aspects of bacterial physiology. ABC transporters are best known for their role in the import of essential nutrients and the export of toxic molecules, but they can also mediate the transport of many other physiological substrates. In a classical transport reaction, two highly conserved ATP-binding domains or subunits couple the binding/hydrolysis of ATP to the translocation of particular substrates across the membrane, through interactions with membrane-spanning domains of the transporter. Variations on this basic theme involve soluble ABC ATP-binding proteins that couple ATP hydrolysis to nontransport processes, such as DNA repair and gene expression regulation. Insights into the structure, function, and mechanism of action of bacterial ABC proteins are reported, based on phylogenetic comparisons as well as classic biochemical and genetic approaches. The availability of an increasing number of high-resolution structures has provided a valuable framework for interpretation of recent studies, and realistic models have been proposed to explain how these fascinating molecular machines use complex dynamic processes to fulfill their numerous biological functions. These advances are also important for elucidating the mechanism of action of eukaryotic ABC proteins, because functional defects in many of them are responsible for severe human inherited diseases.     

Sequence,Structure and Ligand Binding Evolution of Rhodopsin-Like G Protein-Coupled Receptors: A Crystal Structure-Based Phylogenetic Analysis

G protein-coupled receptors (GPCRs) form the largest family of membrane receptors in the human genome. Advances in membrane protein crystallization so far resulted in the determination of 24 receptors available as high-resolution atomic structures. We performed the first phylogenetic analysis of GPCRs based on the available set of GPCR structures. We present a new phylogenetic tree of known human rhodopsin-like GPCR sequences based on this structure set. We can distinguish the three separate classes of small-ligand binding GPCRs, peptide binding GPCRs, and olfactory receptors. Analyzing different structural subdomains, we found that small molecule binding receptors most likely have evolved from peptide receptor precursors, with a rhodopsin/S1PR1 ancestor, most likely an ancestral opsin, forming the link between both classes. A light-activated receptor therefore seems to be the origin of the small molecule hormone receptors of the central nervous system. We find hints for a common evolutionary path of both ligand binding site and central sodium/water binding site. Surprisingly, opioid receptors exhibit both a binding cavity and a central sodium/water binding site similar to the one of biogenic amine receptors instead of peptide receptors, making them seemingly prone to bind small molecule ligands, e.g. opiates. Our results give new insights into the relationship and the pharmacological properties of rhodopsin-like GPCRs.     

Evolution of Primate Social Systems

We review evolutionary processes and mechanisms that gave rise to the diversity of primate social systems. We define social organization, social structure and mating system as distinct components of a social system. For each component, we summarize levels and patterns of variation among primates and discuss evolutionary determinants of this variation. We conclude that conclusive explanations for a solitary life and pair-living are still lacking. We then focus on interactions among the 3 components in order to identify main targets of selection and potential constraints for social evolution. Social organization and mating system are more closely linked to each other than either one is to social structure. Further, we conclude that it is important to seek a priori measures for the effects of presumed selective factors and that the genetic contribution to social systems is still poorly examined. Finally, we examine the role of primate socio-ecology in current evolutionary biology and conclude that primates are not prominently represented because the main questions asked in behavioral ecology are often irrelevant for primate behavior. For the future, we see a rapprochement of these areas as the role of disease and life-history theory are integrated more fully into primate socio-ecology.     

Biosynthesis and Degradation of a Wheat Embryo Cytokinin-Binding Protein during Embryogenesis and Germination

The accumulation and degradation of a wheat (Triticum durum) embryo cytokinin-binding protein (CBF-1) was followed during embryo development and germination by its N⁶-benzyladenine (BA) binding activity and immunological reactivity (rocket immunoelectrophoresis and Western blotting). Both BA binding activity and CBF-1 appeared at 2 weeks post-anthesis and rose sharply between 2 to 4 weeks before leveling off to approximately 47 micrograms per embryo (9% of the soluble embryo protein at maturity). In vitro translation of polyadenylated RNA from 20-day-old embryos yielded a polypeptide which was immunoprecipitable with anti-CBF-1 IgG and migrated closely to the 54-kilodalton CBF-1 polypeptide on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Upon germination, both the amount of CBF-1 and BA binding activity dropped to low levels within 3 days. The data are discussed in relation to the possible role of CBF-1 as a regulator of cytokinin availability, and comparisons are drawn between the structural and biosynthetic similarities found between CBF-1 and the vicilin storage proteins of legumes. An improved method for isolating undegraded CBF-1 from whole seeds is also presented.