Embryology: does prepatterning occur in the mouse egg?

A recurring question in developmental biology has been whether localized determinants play any role in mammalian preimplantation development. This is a controversial issue that brings back the idea of prepatterning and is explored further by Plusa et al., who claim it is the first cleavage of the mouse zygote that predicts the blastocyst axis, rather than the animal pole or sperm entry point, as previously suggested. However, other evidence indicates that the blasotcyst axis is not predetermined and there is no prepatterning in the mouse egg. Here we investigate the origin of these different views and conclude that they arise from differences in the data themselves and in their interpretation.     

Sperm storage induces an immunity cost in ants

Ant queens are among the most long-lived insects known. They mate early in adult life and maintain millions of viable sperm in their sperm storage organ until they die many years later. Because they never re-mate, the reproductive success of queens is ultimately sperm-limited, but it is not known what selective forces determine the upper limit to sperm storage. Here we show that sperm storage carries a significant cost of reduced immunity during colony founding. Newly mated queens of the leaf-cutting ant Atta colombica upregulate their immune response shortly after completing their nest burrow, probably as an adaptive response to a greater exposure to pathogens in the absence of grooming workers. However, the immune response nine days after colony founding is negatively correlated with the amount of sperm in the sperm storage organ, indicating that short-term survival is traded off against long-term reproductive success. The immune response was lower when more males contributed to the stored sperm, indicating that there might be an additional cost of mating or storing genetically different ejaculates.     

New insights into short-chain prenyltransferases: structural features, evolutionary history and potential for selective inhibition

Isoprenoids form an extensive group of natural products involved in a number of important biological processes. Their biosynthesis proceeds through sequential 1′-4 condensations of isopentenyl diphosphate (C₅) with an allylic acceptor, the first of which is dimethylallyl diphosphate (C₅). The reactions leading to the production of geranyl diphosphate (C₁₀), farnesyl diphosphate (C₁₅) and geranylgeranyl diphosphate (C₂₀), which are the precursors of mono-, sesqui- and diterpenes, respectively, are catalyzed by a group of highly conserved enzymes known as short-chain isoprenyl diphosphate synthases, or prenyltransferases. In recent years, the sequences of many new prenyltransferases have become available, including those of several plant and animal geranyl diphosphate synthases, revealing novel mechanisms of product chain-length selectivity and an intricate evolutionary path from a putative common ancestor. Finally, there is considerable interest in designing inhibitors specific to short-chain prenyltransferases, for the purpose of developing new drugs or pesticides that target the isoprenoid biosynthetic pathway.     

Genome duplication in the teleost fish Tetraodon nigroviridis reveals the early vertebrate proto-karyotype

Tetraodon nigroviridis is a freshwater puffer fish with the smallest known vertebrate genome. Here, we report a draft genome sequence with long-range linkage and substantial anchoring to the 21 Tetraodon chromosomes. Genome analysis provides a greatly improved fish gene catalogue, including identifying key genes previously thought to be absent in fish. Comparison with other vertebrates and a urochordate indicates that fish proteins have diverged markedly faster than their mammalian homologues. Comparison with the human genome suggests approximately 900 previously unannotated human genes. Analysis of the Tetraodon and human genomes shows that whole-genome duplication occurred in the teleost fish lineage, subsequent to its divergence from mammals. The analysis also makes it possible to infer the basic structure of the ancestral bony vertebrate genome, which was composed of 12 chromosomes, and to reconstruct much of the evolutionary history of ancient and recent chromosome rearrangements leading to the modern human karyotype.     

Crystal structure and biochemical characterization of the transmembrane PAP2 type phosphatidylglycerol phosphate phosphatase from <Emphasis Type="Italic">Bacillus subtilis</Emphasis>

Type 2 phosphatidic acid phosphatases (PAP2s) can be either soluble or integral membrane enzymes. In bacteria, integral membrane PAP2s play major roles in the metabolisms of glycerophospholipids, undecaprenyl-phosphate (C₅₅-P) lipid carrier and lipopolysaccharides. By in vivo functional experiments and biochemical characterization we show that the membrane PAP2 coded by the Bacillus subtilis yodM gene is the principal phosphatidylglycerol phosphate (PGP) phosphatase of B. subtilis. We also confirm that this enzyme, renamed bsPgpB, has a weaker activity on C₅₅-PP. Moreover, we solved the crystal structure of bsPgpB at 2.25 Å resolution, with tungstate (a phosphate analog) in the active site. The structure reveals two lipid chains in the active site vicinity, allowing for PGP substrate modeling and molecular dynamic simulation. Site-directed mutagenesis confirmed the residues important for substrate specificity, providing a basis for predicting the lipids preferentially dephosphorylated by membrane PAP2s.     

Mutation of RRM2B, encoding p53-controlled ribonucleotide reductase (p53R2), causes severe mitochondrial DNA depletion

Mitochondrial DNA (mtDNA) depletion syndrome (MDS; MIM 251880) is a prevalent cause of oxidative phosphorylation disorders characterized by a reduction in mtDNA copy number. The hitherto recognized disease mechanisms alter either mtDNA replication (POLG (ref. 1)) or the salvage pathway of mitochondrial deoxyribonucleosides 5'-triphosphates (dNTPs) for mtDNA synthesis (DGUOK (ref. 2), TK2 (ref. 3) and SUCLA2 (ref. 4)). A last gene, MPV17 (ref. 5), has no known function. Yet the majority of cases remain unexplained. Studying seven cases of profound mtDNA depletion (1-2% residual mtDNA in muscle) in four unrelated families, we have found nonsense, missense and splice-site mutations and in-frame deletions of the RRM2B gene, encoding the cytosolic p53-inducible ribonucleotide reductase small subunit. Accordingly, severe mtDNA depletion was found in various tissues of the Rrm2b-/- mouse. The mtDNA depletion triggered by p53R2 alterations in both human and mouse implies that p53R2 has a crucial role in dNTP supply for mtDNA synthesis.     

Genomic buffering mitigates the effects of deleterious mutations in bacteria

The relationship between the number of randomly accumulated mutations in a genome and fitness is a key parameter in evolutionary biology. Mutations may interact such that their combined effect on fitness is additive (no epistasis), reinforced (synergistic epistasis) or mitigated (antagonistic epistasis). We measured the decrease in fitness caused by increasing mutation number in the bacterium Salmonella typhimurium using a regulated, error-prone DNA polymerase (polymerase IV, DinB). As mutations accumulated, fitness costs increased at a diminishing rate. This suggests that random mutations interact such that their combined effect on fitness is mitigated and that the genome is buffered against the fitness reduction caused by accumulated mutations. Levels of the heat shock chaperones DnaK and GroEL increased in lineages that had accumulated many mutations, and experimental overproduction of GroEL further increased the fitness of lineages containing deleterious mutations. These findings suggest that overexpression of chaperones contributes to antagonistic epistasis.     

Synchronization of mitosis inPhysarum polycephalum by coalescence of postmitotic and premitotic plasmodial fragments

Zusammenfassung Nach Fusion von promitotischen mit postmitotischen Fragmenten des SchleimpilzesPhysarum polycephalum (Zahlenverhältnis von postmitotischen zu promitotischen Kernen: 1/1) teilten sich die Kerne der so hergestellten Plasmodien synchron.

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Supported by AEC contract No. COO-1432-8.