Sex determination in mammals — Before and after the evolution of SRY

Therian mammals (marsupials and placentals) have an XX female: XY male sex chromosome system, which is homologous to autosomes in other vertebrates. The testis-determining gene, SRY, is conserved on the Y throughout therians, but is absent in other vertebrates, suggesting that the mammal system evolved about 310 million years ago (MYA). However, recent work on the basal monotreme mammals has completely changed our conception of how and when this change occurred. Platypus and echidna lack SRY, and the therian X and Y are represented by autosomes, implying that SRY evolved in therians after their divergence from monotremes only 166 MYA. Clues to the ancestral mechanism usurped by SRY in therians are provided by the monotremes, whose sex chromosomes are homologous to the ZW of birds. This suggests that the therian X and Y, and the SRY gene, evolved from an ancient bird-like sex chromosome system which predates the divergence of mammals and reptiles 310 MYA. Received 4 March 2008; received after revision 22 April 2008; accepted 3 June 2008     

Protein-O-mannosyltransferases in virulence and development

Protein-O-mannosyltransferases (Pmt proteins) catalyse the addition of mannose to serine or threonine residues of secretory proteins. This modification was described first for yeast and later for other fungi, mammals, insects and recently also for bacteria. O-mannosylation depends on specific isoforms of the three Pmt1, 2 and 4 subfamilies. In fungi, O-mannosylation determines the structure and integrity of cell walls, as well as cellular differentiation and virulence. O-mannosylation of specific secretory proteins of the human fungal pathogen Candida albicans and of the bacterial pathogen Mycobacterium tuberculosis contributes significantly to virulence. In mammals and insects, Pmt proteins are essential for cellular differentiation and development, while lack of Pmt activity causes Walker-Warburg syndrome (muscular dystrophy) in humans. The susceptibility of human cells to certain viruses may also depend on O-mannosyl chains. This review focuses on the various roles of Pmt proteins in cellular differentiation, development and virulence. Received 6 September 2007; received after revision 3 October 2007; accepted 5 October 2007     

<Emphasis Type="Italic">Drosophila melanogaster</Emphasis> innate immunity: an emerging role for peptidoglycan recognition proteins in bacteria detection

Over the past years, parallel studies conducted in mammals and flies have emphasized the existence of common mechanisms regulating the vertebrate and invertebrate innate immune systems. This culminated in the discovery of the central role of the Toll pathway in Drosophila immunity and in the implication of Toll-like receptors (TLRs)/interleukin-1(IL-1) in the mammalian innate immune response. In spite of clear similarities, such as shared intracellular pathway components, important divergences are expected between the two groups, whose last common ancestor lived more than half a billion years ago. The most obvious discrepancies lie in the mode of activation of the signalling receptors by microorganisms. In mammals, TLRs are part of protein complexes which directly recognize microbe-associated patterns, whereas Drosophila Toll functions like a classical cytokine receptor rather than a pattern recognition receptor. Recent studies demonstrate that members of the evolutionarily conserved peptidoglycan recognition protein family play an essential role in microbial sensing during immune response of Drosophila.Received 26 June 2003; received after revision 29 July 2003; accepted 25 August 2003     

Serological and genetical studies on the evolution of substrate specificity of flavone glycosyltransferase genes inSilene

Summary The variation in flavone glycosylation patterns inSilene is the result of the expression of six genetic loci, which control either the presence of allozymes differing in substrate specificity or isozymes regulated differently during development. Serological studies showed that at least three of these six loci are evolutionarily related. The genetic mechanisms leading to these complicated variation patterns and the role of this polymorphism for the plant in its interaction with the environment are discussed.     

Molecular neurophysiology of taste in <Emphasis Type="Italic">Drosophila</Emphasis>

The recent identification of candidate receptor genes for sweet, umami and bitter taste in mammals has opened a door to elucidate the molecular and neuronal mechanisms of taste. Drosophila provides a suitable system to study the molecular, physiological and behavioral aspects of taste, as sophisticated molecular genetic techniques can be applied. A gene family for putative gustatory receptors has been found in the Drosophila genome. We discuss here current knowledge of the gustatory physiology of Drosophila. Taste cells in insects are primary sensory neurons whereupon each receptor neuron responds to either sugar, salt or water. We found that particular tarsal gustatory sensilla respond to bitter compounds. Electrophysiological studies indicate that gustatory sensilla on the labellum and tarsi are heterogeneous in terms of their taste sensitivity. Determination of the molecular bases for this heterogeneity could lead to an understanding of how the sensory information is processed in the brain and how this in turn is linked to behavior.Received 12 May 2003; received after revision 9 June 2003; accepted 13 June 2003     

The role of bystin in embryo implantation and in ribosomal biogenesis

Human bystin was identified as a cytoplasmic protein directly binding to trophinin, a cell adhesion molecule potentially involved in human embryo implantation. Although the trophinin gene is unique to mammals, the bystin gene (BYSL) is conserved across eukaryotes. Recent studies show that bystin plays a key role during the transition from silent trophectoderm to an active trophoblast upon trophinin-mediated cell adhesion. Bystin gene knockout and knockdown experiments demonstrate that bystin is essential for embryonic stem cell survival and trophectoderm development in the mouse. Furthermore, biochemical analysis of bystin in human cancer cells and mouse embryos indicates a function in ribosomal biogenesis, specifically in processing of 18S RNA in the 40S subunit. Strong evidence that BYSL is a target of c-MYC is consistent with a role for bystin in rapid protein synthesis, which is required for actively growing cells. Received 30 June 2007; received after revision 7 August 2007; accepted 29 August 2007     

Investigations of receptor-mediated phagocytosis by hormone-induced (imprinted)Tetrahymena pyriformis

Receptor-mediated endocytosis byTetrahvmena pyriformis was studied using tetramethylrhodamine isothiocyanate-labeled concanavalin A (TRITC-Con A) with fluorescence and confocal microscopy. In the presence of insulin, or 24 h after insulin pretreatment (hormonal imprinting), the binding and uptake of TRITC-Con A increased when compared to controls, owing to the binding of TRITC-Con A to sugar oligomers of insulin recptors. Mannose inhibited the binding of Con A, thus demonstrating the specificity of binding. Histamine, a phagocytosis-promoting factor in mammals andTetrahymena, and galactose, did not influence the uptake of TRITC-Con A.     

Hotspots of homologous recombination

Homologous recombination occurs at higher than average frequency at and near hotspots. Hotspots are special nucleotide sequences recognized by proteins that promote, directly or indirectly, a rate limiting step of recombination. This review focuses on two well-studied examples, the Chi sites of the bacteriumEscherichia coli and the M26 site of the fission yeastSchizosaccharomyces pombe. Chi, 5 G-C-T-G-G-T-G-G 3, is recognized by the RecBCD enzyme, which nicks the DNA near Chi and produces a 3-ended single-stranded DNA tail; this tail is a potent substrate for homologous pairing by RecA and single-stranded DNA binding proteins. M26, 5 A-T-G-A-C-G-T 3, is recognized by a heterodimeric protein and stimulates, by an as-yet-unknown mechanism, meiotic recombination at and near theade6 gene. Additional hotspots in bacteria, fungi, and mammals enhance recombination directly or indirectly via a variety of mechanisms. Although hotspots are widespread among organisms, the biological role of their localized enhancement of recombination remains a matter of speculation.     

Genetic control of LDH isozymes in theRana esculenta complex

Summary Studies of LDH isozymes in the European green frogs showed that the synthesis of the B subunits is controlled by 3 alleles at a single genetic locus. The genetic evidence supports the hypothesis thatRana esculenta is the hybrid ofR. lessonae x R. ridibunda.This work was supported by grants from the Schweizerischer Nationalfonds, the Georges und Antoine Claraz-Schenkung and the Karl Hescheler-Stiftung.     

The chromosomal location of phosphatase isozymes of the wheat endosperm

Summary The 7 phosphatase isozymes found in the endosperm of hexaploid wheat (Triticum aestivum L.) are related to chromosomes of homoeology group 4. At least 4 loci are related to phosphatase isozymes.Acknowledgments: The authors thank Dr B. Cifuentes, P. González and E. Wiltshire for technical assistance.     

The presence and function of melatonin and structurally related indoleamines in a dinoflagellate,and a hypothesis on the evolutionary significance of these tryptophan metabolites in unicellulars

The bioluminescent dinoflagellateGonyaulax polyedra contains various indoleamines, in particular, melatonin and 5-methoxytryptamine, as well as enzymes of their biosynthetic pathway. Melatonin exhibits a high-amplitude circadian rhythm characterized by a dramatic increase shortly after the onset of darkness. The maximum of melatonin is followed by a peak of 5-methoxytryptamine. These 5-methoxylated indoleamines seem to be involved in the mediation of the information darkness.G. polyedra shows a short-day response, which consists in the formation of asexual cysts. Light break experiments demonstrate the photoperiodic nature of this reaction. Cells become sensitive to short days only upon exposure to a lowered temperature (<16°C). Melatonin mimics the short-day effect, but only at decreased temperature. 5-Methoxytryptamine is even a better inducer of cyst formation, acting also at 20°C and in any lighting schedule, including LL. Cyst induction is associated with stimulation of bioluminescence and cytoplasmic acidification. A model on the intracellular pathway of photoperiodic information transduction assumes increased deacetylation of melatonin under cyst-inducing conditions, binding of 5-methoxytryptamine to the membrane of an acidic vacuole, proton transfer to the cytoplasm, and decreased intracellular pH as the stimulus for encystment. Melatonin shows the property of a scavenger of superoxide anions. This reaction, which is efficiently catalyzed by hemin, leads to the formation of a substituted kynuramine (AFMK). Destruction of melatonin by light-induced superoxide anions in the presence of cellular hemin may represent a property which, during evolution, has made this molecule suitable as an indicator of darkness. On the other hand, AFMK, which is formed under illumination, might have become a mediator of the information light. Photoperiodism inGonyaulax shows surprising parallels to that in mammals, but allows the analysis of this phenomenon at an entirely cellular level.     

A new cell line (XTY) from a tumor ofXenopus laevis

A new cell line (XTY) was derived from a tumor of a femaleXenopus laevis. This cell line has been proliferating in standard amphibian culture medium for more than 4 years (470 generations) and has a doubling time of 75.5 h at 25°C. The cells aggregate into large groups, and their stellate morphology and the expression of desmin demonstrated by immunocytochemistry suggest that their origin is not epithelial.     

Memory

Our understanding of the cellular and molecular mechanisms underlying learning and memory formation derives from studies of species as diverse as worms, mollusks, insects, birds and mammals. Despite the quite different brain structures and neuronal networks, the studies support the current notion that neuronal activity leads to changes in synaptic connections as the neural substrate of behavioral plasticity. The analysis of the mechanisms underlying learning and memory formation reveals a surprisingly high conservation between invertebrates and mammals, both at the behavioral as well as the molecular level. This special issue provides an overview of the current knowledge on cellular and molecular processes underlying memory formation. The contributing reviews summarize the findings in different organisms, such as Aplysia, Drosophila, honeybees and mammals, and discuss new approaches, developments and hypotheses all aimed at understanding how the nervous system acquires, stores and retrieves information.     

Thiamine triphosphate and thiamine triphosphatase activities: from bacteria to mammals

In most organisms, the main form of thiamine is the coenzyme thiamine diphosphate. Thiamine triphosphate (ThTP) is also found in low amounts in most vertebrate tissues and can phosphorylate certain proteins. Here we show that ThTP exists not only in vertebrates but is present in bacteria, fungi, plants and invertebrates. Unexpectedly, we found that in Escherichia coli as well as in Arabidopsis thaliana, ThTP was synthesized only under particular circumstances such as hypoxia (E. coli) or withering (A. thaliana). In mammalian tissues, ThTP concentrations are regulated by a specific thiamine triphosphatase that we have recently characterized. This enzyme was found only in mammals. In other organisms, ThTP can be hydrolyzed by unspecific phosphohydrolases. The occurrence of ThTP from prokaryotes to mammals suggests that it may have a basic role in cell metabolism or cell signaling. A decreased content may contribute to the symptoms observed during thiamine deficiency.Received 7 March 2003; received after revision 11 April 2003; accepted 14 April 2003     

The role of Ca2+/calmodulin-stimulable adenylyl cyclases as molecular coincidence detectors in memory formation

Evidence from systems as diverse as mollusks, insects and mammals has revealed that adenylyl cyclase, cyclic adenosine 3′,5′-monophosphate (cAMP) cascade, cAMP-dependent protein kinases and their substrates are required for the cellular events underlying the short-term and long-term forms of memory. In Aplysia and Drosophila models, the coincident activation of independent paths converge to produce a synergistic activation of Ca²⁺/calmodulin-stimulable adenylyl cyclase, thereby enhancing the cAMP level that appears as the primary mediator of downstream events that strengthen enduring memory. In mammals, in which long-term memories require hippocampal function, our understanding of the role of adenylyl cyclases is still fragmentary. Of the differently regulated isoforms present in the hippocampus, the susceptibility of type 1 and type 8 to stimulation by the complex Ca²⁺/calmodulin and their expression in the hippocampus suggest a role for these two isoforms as a molecular coincidence device for hippocampus-related memory function. Here, we review the key features of Ca²⁺/calmodulin stimulable adenylyl cyclases, as well as the involvement of cAMP-regulated signaling pathway in the processes of learning and memory.     

Freezing-tolerance in the woodroachCryptocercus punctulatus (Scudder)

Summary Winter-acclimatedCryptocercus punctulatus are able to withstand ice crystal formation within their bodies (freeze-tolerant), and contain hemolymph plasma ice nucleating factors (INF's) throughout the year. In addition, ribitol, a sugar alcohol accumulates in their hemolymph during winter. This represents a new report of INF's occurring in the Dictyoptera, and the presence of ribitol in the hemolymph of the Insecta.Department of Entomology     

The evolutionary history ofDrosophila buzzatii. V. Differential survivorship onOpuntia betweenD. buzzatii andD. serido

Summary Survival time ofDrosophila buzzatii adults on anOpuntia (prickly pear) medium was significantly longer than that of its nearest relativeD. serido. A significant difference was also found betweenD. buzzatii adults from two experimental populations, one of them fed onOpuntia rots for more than two years and another one kept on standardDrosophila medium for the same period of time. These results suggest that adult selection may be taking place in cactiphilicDrosophila in their natural habitats and could be responsible for the niche differentiation betweenD. buzzatii andD. serido.This work has been supported by the Comisión Asesora de investigación Científica y Técnica, Spain, by funds to project 4514/79 awarded to the third author.     

The mammalian NudC-like genes: a family with functions other than regulating nuclear distribution

Nuclear distribution gene C homolog (NudC) is a highly conserved gene. It has been identified in different species from fungi to mammals. The high degree of conservation, in special in the nudC domain, suggests that they are genes with essential functions. Most of the identified genes in the family have been implicated in cell division through the regulation of cytoplasmic dynein. As for mammalian genes, human NUDC has been implicated in the migration and proliferation of tumor cells and has therefore been considered a possible therapeutic target. There is evidence suggesting that mammalian NudC is also implicated in the regulation of the inflammatory response and in thrombopoiesis. The presence of these other functions not related to the interaction with molecular motors agrees with that these genes and their products are larger in size than their microbial orthologous, indicating that they have evolved to convey additional features.     

Electrophoretic variation in esterases in 3 wild-type and respective mutant strains ofAspergillus flavus

Summary Wild-type strains and auxotrophic mutants ofAspergillus flavus, differing regarding aflatoxin production, were tested for esterases isozymes. Esterases variation was found in all strains used, and a possible correlation between the pattern of esterase bands and aflatoxin production is suggested.Acknowledgment. The authors are thankful to the National Council for the development of Science and Technology (CNPq) and Assistance to Research for São Paulo State (FAPESP) for financial assistance.     

Photodecomposition of orellanine and orellinine,the fungal toxins ofCortinarius orellanus Fries andCortinarius speciossimus

Summary The photosensitivity of orellanine, the main toxin ofCortinarius orellanus Fries mushrooms, and its transformation to orelline via orellinine is discussed. All three substances were found in methanolic extracts ofCortinarius orellanus andCortinarius speciossimus mushrooms. The problem of homogeneity of orellanine is also discussed.Acknowledgment. The authors wish to express their gratitude to Prof. Dr W. Steglich from the Institut für Organische Chemie und Biochemie der Universität Bonn (Federal Republic of Germany) for having provided them with a sample of dried material ofC. speciossisimus.