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PubMed2006

Conservation of CD4+ T cell-dependent developmental mechanisms in the blood fluke pathogens of humans.

Schistosoma blood flukes are trematode parasites with a cosmopolitan distribution that infect over 200 million people globally. We previously showed that Schistosoma mansoni growth and development in the mammalian host is dependent on signals from host CD4+ T cells. To gain insight into the mechanisms that underlie this dependence, we sought to determine the evolutionary origins and limits of this aspect of the host-pathogen relationship. By infecting RAG-1-/- mice with a range of different schistosome species and strains, we tested several hypotheses concerning the time during Schistosoma evolution at which this dependence arose, and whether this dependence is specific to Schistosoma or is also found in other blood flukes. Our data indicate that the developmental dependence on CD4+ T cells previously described for S. mansoni is conserved in the evolutionarily basal species Schistosoma japonicum, suggesting this developmental adaptation arose early in Schistosoma evolution. We also demonstrate that the development of the more evolutionarily derived species Schistosoma haematobium and Schistosoma intercalatum are dependent on adaptive immune signals. Together, these data suggest that the blood fluke parasites of humans utilise common mechanisms to infect their hosts and to co-opt immune signals in the coordination of parasite development. Thus, exploitation of host-schistosome interactions to impair or prevent parasite development may represent a novel approach to combating all of the schistosome pathogens of humans.

Animals↗
PubMed2002

Relationships between Staphylococcus aureus genetic background, virulence factors, agr groups (alleles), and human disease.

The expression of most Staphylococcus aureus virulence factors is controlled by the agr locus, which encodes a two-component signaling pathway whose activating ligand is an agr-encoded autoinducing peptide (AIP). A polymorphism in the amino acid sequence of the AIP and of its corresponding receptor divides S. aureus strains into four major groups. Within a given group, each strain produces a peptide that can activate the agr response in the other member strains, whereas the AIPs belonging to different groups are usually mutually inhibitory. We investigated a possible relationship between agr groups and human S. aureus disease by studying 198 S. aureus strains isolated from 14 asymptomatic carriers, 66 patients with suppurative infection, and 114 patients with acute toxemia. The agr group and the distribution of 24 toxin genes were analyzed by PCR, and the genetic background was determined by means of amplified fragment length polymorphism (AFLP) analysis. The isolates were relatively evenly distributed among the four agrgroups, with 61 strains belonging to agr group I, 49 belonging to group II, 43 belonging to group III, and 45 belonging to group IV. Principal coordinate analysis performed on the AFLP distance matrix divided the 198 strains into three main phylogenetic groups, AF1 corresponding to strains of agr group IV, AF2 corresponding to strains of agr groups I and II, and AF3 corresponding to strains of agr group III. This indicated that the agr type was linked to the genetic background. A relationship between genetic background, agr group, and disease type was observed for several toxin-mediated diseases: for instance, agr group IV strains were associated with generalized exfoliative syndromes, and phylogenetic group AF1 strains with bullous impetigo. Among the suppurative infections, endocarditis strains mainly belonged to phylogenetic group AF2 and agr groups I and II. While these results do not show a direct role of the agr type in the type of human disease caused by S. aureus, the agr group may reflect an ancient evolutionary division of S. aureus in terms of this species' fundamental biology.

Alleles↗
PubMed2002

Myogenic regulatory factors and the specification of muscle progenitors in vertebrate embryos.

Embryological and genetic studies of mouse, bird, zebrafish, and frog embryos are providing new insights into the regulatory functions of the myogenic regulatory factors, MyoD, Myf5, Myogenin, and MRF4, and the transcriptional and signaling mechanisms that control their expression during the specification and differentiation of muscle progenitors. Myf5 and MyoD genes have genetically redundant, but developmentally distinct regulatory functions in the specification and the differentiation of somite and head muscle progenitor lineages. Myogenin and MRF4 have later functions in muscle differentiation, and Pax and Hox genes coordinate the migration and specification of somite progenitors at sites of hypaxial and limb muscle formation in the embryo body. Transcription enhancers that control Myf5 and MyoD activation in muscle progenitors and maintain their expression during muscle differentiation have been identified by transgenic analysis. In epaxial, hypaxial, limb, and head muscle progenitors, Myf5 is controlled by lineage-specific transcription enhancers, providing evidence that multiple mechanisms control progenitor specification at different sites of myogenesis in the embryo. Developmental signaling ligands and their signal transduction effectors function both interactively and independently to control Myf5 and MyoD activation in muscle progenitor lineages, likely through direct regulation of their transcription enhancers. Future investigations of the signaling and transcriptional mechanisms that control Myf5 and MyoD in the muscle progenitor lineages of different vertebrate embryos can be expected to provide a detailed understanding of the developmental and evolutionary mechanisms for anatomical muscles formation in vertebrates. This knowledge will be a foundation for development of stem cell therapies to repair diseased and damaged muscles.

Animals↗
PubMed2003

Evolutionary connection between the catalytic subunits of DNA-dependent RNA polymerases and eukaryotic RNA-dependent RNA polymerases and the origin of RNA polymerases.

BACKGROUND: The eukaryotic RNA-dependent RNA polymerase (RDRP) is involved in the amplification of regulatory microRNAs during post-transcriptional gene silencing. This enzyme is highly conserved in most eukaryotes but is missing in archaea and bacteria. No evolutionary relationship between RDRP and other polymerases has been reported so far, hence the origin of this eukaryote-specific polymerase remains a mystery. RESULTS: Using extensive sequence profile searches, we identified bacteriophage homologs of the eukaryotic RDRP. The comparison of the eukaryotic RDRP and their homologs from bacteriophages led to the delineation of the conserved portion of these enzymes, which is predicted to harbor the catalytic site. Further, detailed sequence comparison, aided by examination of the crystal structure of the DNA-dependent RNA polymerase (DDRP), showed that the RDRP and the beta' subunit of DDRP (and its orthologs in archaea and eukaryotes) contain a conserved double-psi beta-barrel (DPBB) domain. This DPBB domain contains the signature motif DbDGD (b is a bulky residue), which is conserved in all RDRPs and DDRPs and contributes to catalysis via a coordinated divalent cation. Apart from the DPBB domain, no similarity was detected between RDRP and DDRP, which leaves open two scenarios for the origin of RDRP: i) RDRP evolved at the onset of the evolution of eukaryotes via a duplication of the DDRP beta' subunit followed by dramatic divergence that obliterated the sequence similarity outside the core catalytic domain and ii) the primordial RDRP, which consisted primarily of the DPBB domain, evolved from a common ancestor with the DDRP at a very early stage of evolution, during the RNA world era. The latter hypothesis implies that RDRP had been subsequently eliminated from cellular life forms and might have been reintroduced into the eukaryotic genomes through a bacteriophage. Sequence and structure analysis of the DDRP led to further insights into the evolution of RNA polymerases. In addition to the beta' subunit, beta subunit of DDRP also contains a DPBB domain, which is, however, distorted by large inserts and does not harbor a counterpart of the DbDGD motif. The DPBB domains of the two DDRP subunits together form the catalytic cleft, with the domain from the beta' subunit supplying the metal-coordinating DbDGD motif and the one from the beta subunit providing two lysine residues involved in catalysis. Given that the two DPBB domains of DDRP contribute completely different sets of active residues to the catalytic center, it is hypothesized that the ultimate ancestor of RNA polymerases functioned as a homodimer of a generic, RNA-binding DPBB domain. This ancestral protein probably did not have catalytic activity and served as a cofactor for a ribozyme RNA polymerase. Subsequent evolution of DDRP and RDRP involved accretion of distinct sets of additional domains. In the DDRPs, these included a RNA-binding Zn-ribbon, an AT-hook-like module and a sandwich-barrel hybrid motif (SBHM) domain. Further, lineage-specific accretion of SBHM domains and other, DDRP-specific domains is observed in bacterial DDRPs. In contrast, the orthologs of the beta' subunit in archaea and eukaryotes contains a four-stranded alpha + beta domain that is shared with the alpha-subunit of bacterial DDRP, eukaryotic DDRP subunit RBP11, translation factor eIF1 and type II topoisomerases. The additional domains of the RDRPs remain to be characterized. CONCLUSIONS: Eukaryotic RNA-dependent RNA polymerases share the catalytic double-psi beta-barrel domain, containing a signature metal-coordinating motif, with the universally conserved beta' subunit of DNA-dependent RNA polymerases. Beyond this core catalytic domain, the two classes of RNA polymerases do not have common domains, suggesting early divergence from a common ancestor, with subsequent independent domain accretion. The beta-subunit of DDRP contains another, highly diverged DPBB domain. The presence of two distinct DPBB domains in two subunits of DDRP is compatible with the hypothesis that the ith the hypothesis that the ultimate ancestor of RNA polymerases was a RNA-binding DPBB domain that had no catalytic activity but rather functioned as a homodimeric cofactor for a ribozyme polymerase.

Amino Acid Sequence↗
PubMedDate not supplied

The development and evolution of the pharyngeal arches.

A muscularised pharynx, with skeletal support, serving the dual functions of feeding and respiration, is a fundamental vertebrate characteristic. Embryologically, the pharyngeal apparatus has its origin in a series of bulges that form on the lateral surface of the embryonic head, the pharyngeal arches, whose development is complex. These structures are composed of a number of disparate embryonic cell types: ectoderm, endoderm, neural crest and mesoderm, whose development must be coordinated to generate the functional adult apparatus. In the past, most studies have emphasised the role played by the neural crest, which generates the skeletal elements of the arches, in directing pharyngeal arch development, but it has also become apparent that the endoderm plays a prominent role in directing arch development. Neural crest cells are not required for arch formation, their regionalisation nor to some extent their sense of identity. Furthermore, the endoderm is the major site of expression of a number of important signalling molecules, and this tissue has been shown to be responsible for promoting the formation of particular components of the arches. Thus vertebrate pharyngeal morphogenesis can now be seen to be a more complex process than was previously believed, and must result from an integration of both neural crest and endodermal patterning mechanisms. Interestingly, this also mirrors the fact that the evolutionary origin of pharyngeal segmentation predates that of the neural crest, which is an exclusively vertebrate characteristic. As such, the evolution of the vertebrate pharynx is also likely to have resulted from an integration between these 2 patterning systems. Alterations in the interplay between neural crest and endodermal patterning are also likely to be responsible for the evolutionary that occurred to the pharyngeal region during subsequent vertebrate evolution.

Animals↗
PubMed2003

Nature versus nurture revisited: an old idea with a new twist.

The nature versus nurture debate has recently resurfaced with the emergence of the field of developmental molecular neurobiology. The questions associated with "nature" have crystallized into testable hypotheses regarding patterns of gene expression during development, and those associated with "nurture" have given over to activity-dependent cellular mechanisms that give rise to variable phenotypes in developing nervous systems. This review focuses on some of the features associated with complex brains and discusses the evolutionary and activity-dependent mechanisms that generate these features. These include increases in the size of the cortical sheet, changes in cortical domain and cortical field specification, and the activity-dependent intracellular mechanisms that regulate the structure and function of neurons during development. We discuss which features are likely to be genetically mediated, which features are likely to be regulated by activity, and how these two mechanisms act in concert to produce the wide variety of phenotypes observed for the mammalian neocortex. For example, the size of the cortical sheet is likely to be under genetic control, and regulation of cell-cycle kinetics through upregulation of genes such as beta-catenin can account for increases in the size of the cortical sheet. Similarly, intrinsic signaling genes or gene products such as Wnt, Shh, Fgf2, Fgf8 and BMP may set up a combinatorial coordinate system that guides thalamic afferents. Changes in peripheral morphology that regulate patterned activity are also likely to be under genetic control. Finally, the intracellular machinery that allows for activity-dependent plasticity in the developing CNS may be genetically regulated, although the specific phenotype they generate are not. On the other hand, aspects of neocortical organization such as sensory domain assignment, the size and shape of cortical fields, some aspects of connectivity, and details of functional organization are likely to be activity-dependent. Furthermore, the role of genes versus activity, and their interactions, may be different for primary fields versus non-primary fields.

Animals↗
PubMed2025

Origin and Evolution of Bacterial Periplasmic Force Transducers.

In double-membraned bacteria, non-equilibrium processes that occur at the outer membrane are typically coupled to the chemiosmotically energized inner membrane. TolA and TonB are homologous proteins which energetically couple inner membrane motor proteins to the essential processes of outer membrane stabilization and substrate import, respectively. The evolutionary trajectories of these proteins have been difficult to elucidate due to low-sequence conservation, yet they are thought to transduce force similarly. Here, this problem was addressed using structural prediction approaches to identify and annotate force transduction operons to trace their distribution and evolutionary origins. In the process, we identify a novel outer membrane-tethering system and a previously unknown family of monomeric force transducers. This approach revealed putative tolA genes, and thus the core organizational principles of the tol-pal operon throughout diverse bacterial taxa. We discovered that the α-helical structure of the periplasm-spanning domain II of TolA previously thought its hallmark, is anomalous amongst most Tol-Pal systems. This structure is mainly prevalent in γ-proteobacteria, likely in adaptation to their lifestyle. Comparison of Tol-Pal and Ton system distribution suggests that TolA emerged from a TonB paralogue and co-emerged with Pal, the outer membrane-tethering lipoprotein that functionalizes the Tol-Pal system. We also determined that TolB, the Pal-mobilizing protein, likely emerged from a family of outer membrane proteins; and CpoB, a periplasmic factor that coordinates peptidoglycan remodeling with cell division, was originally a lipoprotein present in the ancestral Tol-Pal system. The extensive conservation of the Tol-Pal system throughout Gracilicutes highlights its significance in bacterial cell biology.

Evolution, Molecular↗
PubMed2004

The contribution of metal ions to the structural stability of the large ribosomal subunit.

Both monovalent cations and magnesium ions are well known to be essential for the folding and stability of large RNA molecules that form complex and compact structures. In the atomic structure of the large ribosomal subunit from Haloarcula marismortui, we have identified 116 magnesium ions and 88 monovalent cations bound principally to rRNA. Although the rRNA structures to which these metal ions bind are highly idiosyncratic, a few common principles have emerged from the identities of the specific functional groups that coordinate them. The nonbridging oxygen of a phosphate group is the most common inner shell ligand of Mg++, and Mg++ ions having one or two such inner shell ligands are very common. Nonbridging phosphate oxygens and the heteroatoms of nucleotide bases are common outer shell ligands for Mg++ ions. Monovalent cations usually interact with nucleotide bases and protein groups, although some interactions with nonbridging phosphate oxygens are found. The most common monovalent cation binding site is the major groove side of G-U wobble pairs. Both divalent and monovalent cations stabilize the tertiary structure of 23S rRNA by mediating interactions between its structural domains. Bound metal ions are particularly abundant in the region surrounding the peptidyl transferase center, where stabilizing cationic tails of ribosomal proteins are notably absent. This may point to the importance of metal ions for the stabilization of specific RNA structures in the evolutionary period prior to the appearance of proteins, and hence many of these metal ion binding sites may be conserved across all phylogenetic kingdoms.

Base Pairing↗
PubMed1990

The structure of iron superoxide dismutase from Pseudomonas ovalis complexed with the inhibitor azide.

The 2.9 A resolution structure of iron superoxide dismutase (FeSOD) (EC 1.15.1.1) from Pseudomonas ovalis complexed with the inhibitor azide was solved. Comparison of this structure with free enzyme shows that the inhibitor is bound at the open coordination position of the iron, with a bond length of 2.0 A. The metal moves by 0.4 A into the trigonal plane to produce an orthogonal geometry at the iron. Binding of the inhibitor also causes a movement of the axial ligand (histidine 26) away from the metal, a lengthening of the iron-histidine bond, and a rotation of the histidine 74 ring. The inhibitor possesses contacts in the binding pocket with a pair of conserved tryptophan residues and with the side chains of tyrosine 34 and glutamine 70. This glutamine is conserved between all FeSODs, but is absent in MnSOD. Comparisons with MnSOD show that a different glutamine which possesses the same interactions in the active site as Gln70 in FeSOD is conserved at position 154 in the overall SOD sequence, implying that while manganese and FeSODs are structural homologues in a global sense, their functional and evolutionary relationship is that of second-site mutation revertants.

Amino Acid Sequence↗
PubMed1999

Evolution and development of a central pattern generator for the swimming of a lamprey.

This article describes the design of neural control architectures for locomotion using an evolutionary approach. Inspired by the central pattern generators found in animals, we develop neural controllers that can produce the patterns of oscillations necessary for the swimming of a simulated lamprey. This work is inspired by Ekeberg's neuronal and mechanical model of a lamprey [11] and follows experiments in which swimming controllers were evolved using a simple encoding scheme [25, 26]. Here, controllers are developed using an evolutionary algorithm based on the SGOCE encoding [31, 32] in which a genetic programming approach is used to evolve developmental programs that encode the growing of a dynamical neural network. The developmental programs determine how neurons located on a two-dimensional substrate produce new cells through cellular division and how they form efferent or afferent interconnections. Swimming controllers are generated when the growing networks eventually create connections to the muscles located on both sides of the rectangular substrate. These muscles are part of a two-dimensional mechanical simulation of the body of the lamprey in interaction with water. The motivation of this article is to develop a method for the design of control mechanisms for animal-like locomotion. Such a locomotion is characterized by a large number of actuators, a rhythmic activity, and the fact that efficient motion is only obtained when the actuators are well coordinated. The task of the control mechanism is therefore to transform commands concerning the speed and direction of motion into the signals sent to the multiple actuators. We define a fitness function, based on several simulations of the controller with different commands settings, that rewards the capacity of modulating the speed and the direction of swimming in response to simple, varying input signals. Central pattern generators are thus evolved capable of producing the relatively complex patterns of oscillations necessary for swimming. The best solutions generate traveling waves of neural activity, and propagate, similarly to the swimming of a real lamprey, undulations of the body from head to tail propelling the lamprey forward through water. By simply varying the amplitude of two input signals, the speed and the direction of swimming can be modulated.

Algorithms↗
PubMed1988

Substitution of murine for human CD4 residues identifies amino acids critical for HIV-gp120 binding.

Human CD4 is the receptor for the gp120 envelope glycoprotein of human immunodeficiency virus and is essential for virus entry into the host cell. Sequence analysis of CD4 has suggested an evolutionary origin from a structure with four immunoglobulin-related domains. Only the two NH2-terminal domains are required to mediate gp120 binding. The extracellular segment of murine CD4 has an overall 50% identity with its human counterpart at the amino-acid level, but fails to bind gp120. To define those residues of human CD4 critical for gp120 binding, we have taken advantage of this species difference and substituted all non-conserved murine for human CD4 residues between amino-acid positions 27-167. We used oligonucleotide-directed mutagenesis to create each of 16 individual mutant human CD4 molecules containing from 1-4 amino-acid substitutions. Introduction of as few as three amino acids into corresponding positions of human CD4 abrogates gp120 binding. Furthermore, these critical residues are located in domain I with a contribution from domain II. Modelling studies using the three-dimensional coordinates of the V kappa Bence-Jones REI homodimer localize the site in domain I to the C" beta strand within CDR2 but projecting away from the homologues of principle antigen-binding regions CDR 1 and 3.

Amino Acid Sequence↗
PubMed2003

Phylogeny of a growth hormone-like cytokine superfamily based upon 3D structure.

Cytokines are of central importance in the regulation of hematopoiesis, immunity, inflammation, tissue remodeling, and embryonic development. Cytokine research is expected to provide the key to pharmacological manipulation of the immune response and commands the attention of a massive and highly focused biotechnology industry. Based upon the hypothetical secondary and tertiary structures, a superfamily of growth hormone (GH)-like cytokine was identified previously. Here, we report the phylogeny of this superfamily based upon 3D structural data from the Protein Data Bank. First, a retrieving program is designed to abstract their secondary structures and associated atomic coordinates. Helices, digitized as vectors in the Cartesian coordinate system, are collected from the retrieved atomic coordinates at the alpha carbons of the protein backbone. Then the scalar value and vector angle against the reference vector, usually the first vector, are calculated. Furthermore, cluster analysis among various cytokines is performed on their helical scales and helical angles. As a result, GH is close to the cluster formed by ciliary neurotrophic factor and granulocyte colony-stimulating factor (CSF); leptin and erythropoietin are in descending order close to the cluster formed by interleukin (IL)-6 and IL-10; the former seven members in the two subgroups above join together and form one group with leukemia inhibitory factor; granulocyte-macrophage CSF, IL-2, IL-4, and IL-5 are in descending order close to the cluster formed by IL-3 and macrophage CSF; and the latter six members form another group. Finally, it is demonstrated that the phylogeny of GH-like cytokines above is consistent with the evolutionary relationship of their gene organization, gene localization, receptor module composition, and receptor module compatibility.

Animals↗
PubMed2005

Structure of Escherichia coli RNase E catalytic domain and implications for RNA turnover.

The coordinated regulation of gene expression is required for homeostasis, growth and development in all organisms. Such coordination may be partly achieved at the level of messenger RNA stability, in which the targeted destruction of subsets of transcripts generates the potential for cross-regulating metabolic pathways. In Escherichia coli, the balance and composition of the transcript population is affected by RNase E, an essential endoribonuclease that not only turns over RNA but also processes certain key RNA precursors. RNase E cleaves RNA internally, but its catalytic power is determined by the 5' terminus of the substrate, even if this lies at a distance from the cutting site. Here we report crystal structures of the catalytic domain of RNase E as trapped allosteric intermediates with RNA substrates. Four subunits of RNase E catalytic domain associate into an interwoven quaternary structure, explaining why the subunit organization is required for catalytic activity. The subdomain encompassing the active site is structurally congruent to a deoxyribonuclease, making an unexpected link in the evolutionary history of RNA and DNA nucleases. The structure explains how the recognition of the 5' terminus of the substrate may trigger catalysis and also sheds light on the question of how RNase E might selectively process, rather than destroy, specific RNA precursors.

Allosteric Regulation↗
PubMed2002

Reaction mechanism, evolutionary analysis, and role of zinc in Drosophila methionine-R-sulfoxide reductase.

Methionine residues in proteins are susceptible to oxidation, and the resulting methionine sulfoxides can be reduced back to methionines by methionine-S-sulfoxide reductase (MsrA) and methionine-R-sulfoxide reductase (MsrB). Herein, we have identified two MsrB families that differ by the presence of zinc. Evolutionary analyses suggested that the zinc-containing MsrB proteins are prototype enzymes and that the metal was lost in certain MsrB proteins later in evolution. Zinc-containing Drosophila MsrB was further characterized. The enzyme was found to employ a catalytic Cys(124) thiolate, which directly interacted with methionine sulfoxide, resulting in methionine and a Cys(124) sulfenic acid intermediate. A subsequent reaction of this intermediate with Cys(69) generated an intramolecular disulfide. Dithiothreitol could reduce either the sulfenic acid or the disulfide, but the disulfide was a preferred substrate for thioredoxin, a natural electron donor. Interestingly, the C69S mutant could complement MsrA/MsrB deficiency in yeast, and the corresponding natural form of mouse MsrB was active with thioredoxin. These data indicate that MsrB proteins employ alternative mechanisms for sulfenic acid reduction. Four other conserved cysteines in Drosophila MsrB (Cys(51), Cys(54), Cys(101), and Cys(104)) were found to coordinate structural zinc. Mutation of any one or a combination of these residues resulted in complete loss of metal and catalytic activity, demonstrating an essential role of zinc in Drosophila MsrB. In contrast, two conserved histidines were important for thioredoxin-dependent activity, but were not involved in zinc binding. A Drosophila MsrA gene was also cloned, and the recombinant enzyme was found to be metal-free and specific for methionine S-sulfoxide and to employ a similar sulfenic acid/disulfide mechanism.

Amino Acid Sequence↗
PubMed2005

Pheromone reception in mammals.

Pheromonal communication is the most convenient way to transfer information regarding gender and social status in animals of the same species with the holistic goal of sustaining reproduction. This type of information exchange is based on pheromones, molecules often chemically unrelated, that are contained in body fluids like urine, sweat, specialized exocrine glands, and mucous secretions of genitals. So profound is the relevance of pheromones over the evolutionary process that a specific peripheral organ devoted to their recognition, namely the vomeronasal organ of Jacobson, and a related central pathway arose in most vertebrate species. Although the vomeronasal system is well developed in reptiles and amphibians, most mammals strongly rely on pheromonal communication. Humans use pheromones too; evidence on the existence of a specialized organ for their detection, however, is very elusive indeed. In the present review, we will focus our attention on the behavioral, physiological, and molecular aspects of pheromone detection in mammals. We will discuss the responses to pheromonal stimulation in different animal species, emphasizing the complicacy of this type of communication. In the light of the most recent results, we will also discuss the complex organization of the transduction molecules that underlie pheromone detection and signal transmission from vomeronasal neurons to the higher centers of the brain. Communication is a primary feature of living organisms, allowing the coordination of different behavioral paradigms among individuals. Communication has evolved through a variety of different strategies, and each species refined its own preferred communication medium. From a phylogenetic point of view, the most widespread and ancient way of communication is through chemical signals named pheromones: it occurs in all taxa, from prokaryotes to eukaryotes. The release of specific pheromones into the environment is a sensitive and definite way to send messages to other members of the same species. Therefore, the action of an organism can alter the behavior of another organism, thereby increasing the fitness of either or both. Albeit slow in transmission and not easily modulated, pheromones can travel around objects in the dark and over long distances. In addition, they are emitted when necessary and their biosynthesis is usually economic. In essence, they represent the most efficient tool to refine the pattern of social behaviors and reproductive strategies.

Animals↗
PubMed1987

Comparison of the cis-acting control regions of two coordinately controlled genes involved in ethanol utilization in Aspergillus nidulans.

The alcA and aldA genes of Aspergillus nidulans are regulated in exactly the same manner, being subject to positive control by the product of the alcR gene. We report the complete nucleotide sequence of the alcA gene and its 5' non-coding region, preliminary localization of the region involved in the regulation of alcA expression, and a detailed comparison of this region to the 5' non-coding region of aldA (Pickett et al., 1987). The 5' flanking regions of the genes contain six similar sequence elements. Three of these elements are located upstream from the messenger RNA start points and one is related to a sequence element found in the region responsible for ethanol induction of the yeast ADH2 gene (Beier et al., 1985). The other homologous elements are located within the messenger RNA leader and may be associated with selection of messenger RNA start points. The amino acid sequence of alcohol dehydrogenase I (348 residues) shows a significant level of homology with analogous sequences in other organisms. Gene alcA contains introns which are similar in size and structure to other fungal introns. We discuss the positions of the introns in alcA of A. nidulans with particular reference to the conservation of intron position in and the evolutionary assembly of enzymes which possess NAD-binding domains.

Alcohol Dehydrogenase↗
PubMed2000

Marsupial cytokines. Structure, function and evolution.

The cytokines are an important group of molecules involved in coordinating the many and varied components of the immune system. These molecules have been extensively studied in model eutherian mammals such as mice but comparatively little is known about the cytokine network of marsupials. Such information will be invaluable in elucidating fundamental aspects of the marsupial immune system and will also highlight parallels and differences between the immune systems of marsupials and eutherians. Given the importance of these goals, our groups have recently begun to tackle this lack of knowledge of the marsupial cytokine system and have met with considerable success in the face of the rapid rate of change of these proteins. This has led to the isolation of the full-length sequences encoding marsupial orthologues of tumour necrosis factor (TNF), lymphotoxins alpha and beta (LT-alpha and beta), interleukin-1 beta (IL-1beta), and interleukin-10 (IL-10). Here we review what has been learnt about structural, functional and evolutionary aspects of these marsupial cytokines as well as briefly describing more recent work in progress and future directions in this field.

Animals↗
PubMed2003

Direct and concentration-dependent regulation of the proneural gene Neurogenin2 by Pax6.

Expression of the proneural gene Neurogenin2 is controlled by several enhancer elements, with the E1 element active in restricted progenitor domains in the embryonic spinal cord and telencephalon that express the homeodomain protein Pax6. We show that Pax6 function is both required and sufficient to activate this enhancer, and we identify one evolutionary conserved sequence in the E1 element with high similarity to a consensus Pax6 binding site. This conserved sequence binds Pax6 protein with low affinity both in vitro and in vivo, and its disruption results in a severe decrease in E1 activity in the spinal cord and in its abolition in the cerebral cortex. The regulation of Neurogenin2 by Pax6 is thus direct. Pax6 is expressed in concentration gradients in both spinal cord and telencephalon. We demonstrate that the E1 element is only activated by high concentrations of Pax6 protein, and that this requirement explains the restriction of E1 enhancer activity to domains of high Pax6 expression levels in the medioventral spinal cord and lateral cortex. By modifying the E1 enhancer sequence, we also show that the spatial pattern of enhancer activity is determined by the affinity of its binding site for Pax6. Together, these data demonstrate that direct transcriptional regulation accounts for the coordination between mechanisms of patterning and neurogenesis. They also provide evidence that Pax6 expression gradients are involved in establishing borders of gene expression domains in different regions of the nervous system.

Animals↗