Evolution of dosage compensation

In polytene chromosome squashes from the fruit flyDrosophila melanogaster, the single, dosage-compensated X chromosome in males can be distinguished from the autosomes by the presence of an isoform of histone H4 acetylated at lysine 16, H4.Ac16. We have used H4.Ac16 as a marker to examine the evolving relationship between dosage compensation and sex chromosome composition in species ofDrosophila with one (D. melanogaster), two (D. pseudoobscura) or three (D. miranda) identifiable X chromosome arms. In each case, we find that H4.Ac16 is distributed as discrete, closely spaced bands along the entire length of each X chromosome, the only exception being the X2 chromosome ofD. miranda in which a terminal region constituting about 10% of the chromosome by length is not labelled with anti-H4.Ac16 antibodies. We conclude that, with this exception, dosage compensation extends along the X chromosomes of all three species. AsD. pseudoobscura andD. miranda diverged only about 2 Mya, the spread of dosage-compensated loci along X2 has been rapid, suggesting that regional changes rather than piecemeal, gene-by-gene, changes may have been involved.accepted for publication by H. C. Macgregor     

Misexpression screen delineates novel genes controlling Drosophila lifespan

In an initial preliminary screen we identified factors associated with controlling Drosophila aging by examining longevity in adults where EP elements induced over-expression or antisense-RNA at genes adjacent to each insertion. Here, we study 45 EP lines that initially showed at least 10% longer mean lifespan than controls. These 45 lines and a daughterless (da)-Gal4 stock were isogenized into a CS10 wild-type background. Sixteen EP lines corresponding to 15 genes significantly extended lifespan when their target genes were driven by da-Gal4. In each case, the target genes were seen to be over-expressed. Independently derived UAS-gene transgenic stocks were available or made for two candidates: ImpL2 which is ecdysone-inducible gene L2, and CG33138, 1,4-alpha-glucan branching enzyme. With both, adult lifespan was increased upon over-expression via the GeneSwitch inducible Gal4 driver system. Several genes in this set of 15 correspond to previously discovered longevity assurance systems such as insulin/IGF-1 signaling, gene silencing, and autophagy; others suggest new potential mechanisms for the control of aging including mRNA synthesis and maturation, intracellular vesicle trafficking, and neuroendocrine regulation.     

Error-prone polyploid mitosis during normal Drosophila development

Endopolyploidy arises during normal development in many species when cells undergo endocycles-variant cell cycles in which DNA replicates but daughter cells do not form. Normally, polyploid cells do not divide mitotically after initiating endocycles; hence, little is known about their mitotic competence. However, polyploid cells are found in many tumors, and the enhanced chromosomal instability of polyploid cells in culture suggests that such cells contribute to tumor aneuploidy. Here, we describe a novel polyploid Drosophila cell type that undergoes normal mitotic cycles as part of a remodeling process that forms the adult rectal papillae. Similar polyploid mitotic divisions, but not depolyploidizing divisions, were observed during adult ileum development in the mosquito Culex pipiens. Extended anaphases, chromosome bridges, and lagging chromosomes were frequent during these polyploid divisions, despite normal expression of cell cycle regulators. Our results show that the switch to endocycles during development is not irreversible, but argue that the polyploid mitotic cycle is inherently error-prone, and that polyploid mitoses may help destabilize the cancer genome.     

A master CLOCK hard at work brings rhythm to the transcriptome

In this issue of Genes & Development, Abruzzi et al. (pp. 2374–2386) use chromatin immunoprecipitation (ChIP) tiling array assays (ChIP–chip) to show that physical interactions between circadian (≅24-h) clock machineries and genomes are more widespread than previously thought and provide novel insights into how clocks drive daily rhythms in global gene expression.     

The SLC36 transporter Pathetic is required for extreme dendrite growth in Drosophila sensory neurons

Dendrites exhibit enormous diversity in form and can differ in size by several orders of magnitude even in a single animal. However, whether neurons with large dendrite arbors have specialized mechanisms to support their growth demands is unknown. To address this question, we conducted a genetic screen for mutations that differentially affected growth in neurons with different-sized dendrite arbors. From this screen, we identified a mutant that selectively affects dendrite growth in neurons with large dendrite arbors without affecting dendrite growth in neurons with small dendrite arbors or the animal overall. This mutant disrupts a putative amino acid transporter, Pathetic (Path), that localizes to the cell surface and endolysosomal compartments in neurons. Although Path is broadly expressed in neurons and nonneuronal cells, mutation of path impinges on nutrient responses and protein homeostasis specifically in neurons with large dendrite arbors but not in other cells. Altogether, our results demonstrate that specialized molecular mechanisms exist to support growth demands in neurons with large dendrite arbors and define Path as a founding member of this growth program.     

Drosophila PTB promotes formation of high-order RNP particles and represses oskar translation

Local translation of asymmetrically enriched mRNAs is a powerful mechanism for functional polarization of the cell. In Drosophila, exclusive accumulation of Oskar protein at the posterior pole of the oocyte is essential for development of the future embryo. This is achieved by the formation of a dynamic oskar ribonucleoprotein (RNP) complex regulating the transport of oskar mRNA, its translational repression while unlocalized, and its translational activation upon arrival at the posterior pole. We identified the nucleo–cytoplasmic shuttling protein PTB (polypyrimidine tract-binding protein)/hnRNP I as a new factor associating with the oskar RNP in vivo. While PTB function is largely dispensable for oskar mRNA transport, it is necessary for translational repression of the localizing mRNA. Unexpectedly, a cytoplasmic form of PTB can associate with oskar mRNA and repress its translation, suggesting that nuclear recruitment of PTB to oskar complexes is not required for its regulatory function. Furthermore, PTB binds directly to multiple sites along the oskar 3′ untranslated region and mediates assembly of high-order complexes containing multiple oskar RNA molecules in vivo. Thus, PTB is a key structural component of oskar RNP complexes that dually controls formation of high-order RNP particles and translational silencing.