Organization of Physical Interactomes as Uncovered by Network Schemas

Large-scale protein-protein interaction networks provide new opportunities for understanding cellular organization and functioning. We introduce network schemas to elucidate shared mechanisms within interactomes. Network schemas specify descriptions of proteins and the topology of interactions among them. We develop algorithms for systematically uncovering recurring, over-represented schemas in physical interaction networks. We apply our methods to the S. cerevisiae interactome, focusing on schemas consisting of proteins described via sequence motifs and molecular function annotations and interacting with one another in one of four basic network topologies. We identify hundreds of recurring and over-represented network schemas of various complexity, and demonstrate via graph-theoretic representations how more complex schemas are organized in terms of their lower-order constituents. The uncovered schemas span a wide range of cellular activities, with many signaling and transport related higher-order schemas. We establish the functional importance of the schemas by showing that they correspond to functionally cohesive sets of proteins, are enriched in the frequency with which they have instances in the H. sapiens interactome, and are useful for predicting protein function. Our findings suggest that network schemas are a powerful paradigm for organizing, interrogating, and annotating cellular networks

Comparaison radiologique des techniques de mesure du prognathisme.

Wangermez J., Despons J.-L. Comparaison radiologique des techniques de mesure du prognathisme.. In: Bulletins et Mémoires de la Société d'anthropologie de Paris, XI° Série. Tome 6 fascicule 2, 1964. pp. 313-338

Differential evolution of the Saccharomyces cerevisiae DUP240 paralogs and implication of recombination in phylogeny

Multigene families are observed in all genomes sequenced so far and are the reflection of key evolutionary mechanisms. The DUP240 family, identified in Saccharomyces cerevisiae strain S288C, is composed of 10 paralogs: seven are organized as two tandem repeats and three are solo ORFs. To investigate the evolution of the three solo paralogs, YAR023c, YCR007c and YHL044w, we performed a comparative analysis between 15 S.cerevisiae strains. These three ORFs are present in all strains and the conservation of synteny indicates that they are not frequently involved in chromosomal reshaping, in contrast to the DUP240 ORFs organized in tandem repeats. Our analysis of nucleotide and amino acid variations indicates that YAR023c and YHL044w fix mutations more easily than YCR007c, although they all belong to the same multigene family. This comparative analysis was also conducted with five arbitrarily chosen Ascomycetes-specific genes and five arbitrarily chosen common genes (genes that have a homolog in at least one non-Ascomycetes organism). Ascomycetes-specific genes appear to be diverging faster than common genes in the S.cerevisiae species, a situation that was previously described between different yeast species. Our results point to the strong contribution, during DNA sequence evolution, of allelic recombination besides nucleotide substitution

Paleogenomics or the search for remnant duplicated copies of the yeast DUP240 gene family in intergenic areas.

Duplication, resulting in gene redundancy, is well known to be a driving force of evolutionary change. Gene families are therefore useful targets for approaching genome evolution. To address the gene death process, we examined the fate of the 10-member-large S288C DUP240 family in 15 Saccharomyces cerevisiae strains. Using an original three-step method of analysis reported here, both slightly and highly degenerate DUP240 copies, called pseudo-open reading frames (ORFs) and relics, respectively, were detected in strain S288C. It was concluded that two previously annotated ORFs correspond, in fact, to pseudo-ORFs and three additional relics were identified in intergenic areas. Comparative intraspecies analysis of these degenerate DUP240 loci revealed that the two pseudo-ORFs are present in a nondegenerate state in some other strains. This suggests that within a given gene family different loci are the target of the gene erasure process, which is therefore strain dependent. Besides, the variable positions observed indicate that the relic sequence may diverge faster than the flanking regions. All in all, this study shows that short conserved protein motifs provide a useful tool for detecting and accurately mapping degenerate gene remnants. The present results also highlight the strong contribution of comparative genomics for gene relic detection because the possibility of finding short conserved protein motifs in intergenic regions (IRs) largely depends on the choice of the most closely related paralog or ortholog. By mapping new genetic components in previously annotated IRs, our study constitutes a further refinement step in the crucial stage of genome annotation and provides a strategy for retracing ancient chromosomal reshaping events and, hence, for deciphering genome history.historical articlejournal articleresearch support, non-u.s. gov't2005 Sep2005 05 25importe

An evolutionary scenario for one of the largest yeast gene families.

The DUP gene family of Saccharomyces cerevisiae comprises 23 members that can be divided into two subfamilies--DUP240 and DUP380. The location of the DUP loci suggests that at least three mechanisms were responsible for their genomic dispersion: nonreciprocal translocation at chromosomal ends, tandem duplication and Ty-associated duplication. The data we present here suggest that these nonessential genes encode proteins that facilitate membrane trafficking processes. Dup240 proteins have three conserved domains (C1, C2 and C3) and two predicted transmembrane segments (H1 and H2). A direct repetition of the C1-H1-H2-C2 module is observed in Dup380p sequences. In this article, we propose an evolutionary model to account for the emergence of the two gene subfamilies.journal articleresearch support, non-u.s. gov't2006 Jan2005 11 02importe

Functional analysis of the Saccharomyces cerevisiae DUP240 multigene family reveals membrane-associated proteins that are not essential for cell viability.

The DUP240 gene family of Saccharomyces cerevisiae is composed of 10 members. They encode proteins of about 240 amino acids which contain two predicted transmembrane domains. Database searches identified only one homologue in the closely related species Saccharomyces bayanus, indicating that the DUP240 genes encode proteins specific to Saccharomyces sensu stricto. The short-flanking homology PCR gene-replacement strategy with a variety of selective markers for replacements, and classical genetic methods, were used to generate strains deleted for all 10 DUP240 genes. All of the knock-out strains were viable and had similar growth kinetics to the wild-type. Two-hybrid screens, hSos1p fusions and GFP fusions were carried out; the results indicated that the Dup240 proteins are membrane associated, and that some of them are concentrated around the plasma membrane.journal articleresearch support, non-u.s. gov't2002 Julimporte

In cell mutational interference mapping experiment (in cell MIME) identifies the 5' polyadenylation signal as a dual regulator of HIV - 1 genomic RNA production and packaging

International audienc

Role of Arc1p in the modulation of yeast glutamyl-tRNA synthetase activity

Yeast methionyl-tRNA synthetase (MetRS) and glutamyl-tRNA synthetase (GluRS) possess N-terminal extensions that bind the cofactor Arc1p in trans. The strength of GluRS-Arc1p interaction is high enough to allow copurification of the two macromolecules in a 1:1 ratio, in contrast to MetRS. Deletion analysis from the C-terminal end of the GluRS appendix combined with previous N-terminal deletions of GluRS allows restriction of the Arc1p binding site to the 110-170 amino acid region of GluRS. This region has been shown to correspond to a novel protein-protein interaction domain present in both GluRS and Arc1p but not in MetRS [Galani, K., Grosshans, H., Deinert, K., Hurt, E. C., and Simos, G. (2001) EMBO J. 20, 6889-6898]. The GluRS apoenzyme fails to show significant kinetics of tRNA aminoacylation and charges unfractionated yeast tRNA at a level 10-fold reduced compared to Arc1p-bound GluRS. The Km values for tRNA Glu measured in the ATP-PPi exchange were similar for the two forms of GluRS, whereas kcat is increased 2-fold in the presence of Arc1p. Band-shift analysis revealed a 100-fold increase in tRNA binding affinity when Arc1p is bound to GluRS. This increase requires the RNA binding properties of the full-length Arc1p since Arc1p N domain leaves the K d of GluRS for tRNA unchanged. Transcripts of yeast tRNA Glu were poor substrates for measuring tRNA aminoacylation and could not be used to clarify whether Arc1p has a specific effect on the tRNA charging reaction