Turning gold into 'junk': transposable elements utilize central proteins of cellular networks

The numerous discovered cases of domesticated transposable element (TE) proteins led to the recognition that TEs are a significant source of evolutionary innovation. However, much less is known about the reverse process, whether and to what degree the evolution of TEs is influenced by the genome of their hosts. We addressed this issue by searching for cases of incorporation of host genes into the sequence of TEs and examined the systems-level properties of these genes using the Saccharomyces cerevisiae and Drosophila melanogaster genomes. We identified 51 cases where the evolutionary scenario was the incorporation of a host gene fragment into a TE consensus sequence, and we show that both the yeast and fly homologues of the incorporated protein sequences have central positions in the cellular networks. An analysis of selective pressure (Ka/Ks ratio) detected significant selection in 37% of the cases. Recent research on retrovirus-host interactions shows that virus proteins preferentially target hubs of the host interaction networks enabling them to take over the host cell using only a few proteins. We propose that TEs face a similar evolutionary pressure to evolve proteins with high interacting capacities and take some of the necessary protein domains directly from their hosts

Structure Prediction and Analysis of DNA Transposon and LINE Retrotransposon Proteins

Despite the considerable amount of research on transposable elements, no large-scale structural analyses of the TE proteome have been performed so far. We predicted the structures of hundreds of proteins from a representative set of DNA and LINE transposable elements and used the obtained structural data to provide the first general structural characterization of TE proteins and to estimate the frequency of TE domestication and horizontal transfer events. We show that 1) ORF1 and Gag proteins of retrotransposons contain high amounts of structural disorder; thus, despite their very low conservation, the presence of disordered regions and probably their chaperone function is conserved. 2) The distribution of SCOP classes in DNA transposons and LINEs indicates that the proteins of DNA transposons are more ancient, containing folds that already existed when the first cellular organisms appeared. 3) DNA transposon proteins have lower contact order than randomly selected reference proteins, indicating rapid folding, most likely to avoid protein aggregation. 4) Structure-based searches for TE homologs indicate that the overall frequency of TE domestication events is low, whereas we found a relatively high number of cases where horizontal transfer, frequently involving parasites, is the most likely explanation for the observed homology

Contradiction and grammar : the case of weak islands

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Linguistics and Philosophy, 2007.Includes bibliographical references (p. 135-138).This thesis is about weak islands. Weak islands are contexts that are transparent to some but not all operator-variable dependencies. For this reason, they are also sometimes called selective islands. Some paradigmatic cases of weak island violations include the ungrammatical examples involving manner and degree extraction in (1)a and (2)a, as opposed to the acceptable questions about individuals in (1)b and (2)b: (1) a. *How does John regret that he fixed the car? b.Who does John regret that he invited to the party? (2) a. *How much milk haven't you spilled on your shirt? b.Which girl haven't you introduced to Mary? The main questions that an account of weak islands should address are the following: * What contexts create weak islands and why? + Which expressions are sensitive to weak islands and why? * Why do weak islands sometimes improve? This thesis develops a semantic account for weak islands, whose core idea can be summarized as follows. What sets apart the expressions that are sensitive to weak islands from the ones that are not is that in the case of the former the domain of quantification is such that its elements stand in a particular logical relationship with each other. The island creating contexts are those in which this property of the island-sensitive expressions leads to a problem, namely a contradiction. This contradiction might manifest itself in one of two forms: In some cases, the question will presuppose that that a number of mutually incompatible alternatives is true at the same time, therefore it will necessarily lead to a presupposition failure in any context.(cont.) In other cases, the presupposition that there be a complete answer will not be met in any context, because the domain of question alternatives will always contain at least two alternatives that have to-but cannot-be ruled out at the same time. The present proposal therefore fits in the family of proposals (most importantly Szabolcsi and Zwarts (1993), Honcoop (1998), Rullmann (1995), Fox and Hackl (2005)) which argue that it is independently necessary principles of semantic composition that lead to the oddness of weak islands, rather than abstract syntactic locality constraints. As such, it provides a further piece of evidence against the view which holds that principles governing the well-formedness of sentences necessarily belong to the realm of syntax as we know it. However, when we will examine the nature of the contradiction that arises in the cases of weak island violations, we will observe that it is only a special type of contradiction-identified by Gajewski (2002) as L-analytic-which leads to ungrammaticality: namely one that results from the logical constants of the sentence alone. In this sense the violation that can be observed might be argued to be "syntactic": it can be read from the logical form of the sentences.by Márta Abrusán.Ph.D

Evolutionary History of Mammalian Transposons Determined by Genome-Wide Defragmentation

The constant bombardment of mammalian genomes by transposable elements (TEs) has resulted in TEs comprising at least 45% of the human genome. Because of their great age and abundance, TEs are important in comparative phylogenomics. However, estimates of TE age were previously based on divergence from derived consensus sequences or phylogenetic analysis, which can be unreliable, especially for older more diverged elements. Therefore, a novel genome-wide analysis of TE organization and fragmentation was performed to estimate TE age independently of sequence composition and divergence or the assumption of a constant molecular clock. Analysis of TEs in the human genome revealed ∼600,000 examples where TEs have transposed into and fragmented other TEs, covering >40% of all TEs or ∼542 Mbp of genomic sequence. The relative age of these TEs over evolutionary time is implicit in their organization, because newer TEs have necessarily transposed into older TEs that were already present. A matrix of the number of times that each TE has transposed into every other TE was constructed, and a novel objective function was developed that derived the chronological order and relative ages of human TEs spanning >100 million years. This method has been used to infer the relative ages across all four major TE classes, including the oldest, most diverged elements. Analysis of DNA transposons over the history of the human genome has revealed the early activity of some MER2 transposons, and the relatively recent activity of MER1 transposons during primate lineages. The TEs from six additional mammalian genomes were defragmented and analyzed. Pairwise comparison of the independent chronological orders of TEs in these mammalian genomes revealed species phylogeny, the fact that transposons shared between genomes are older than species-specific transposons, and a subset of TEs that were potentially active during periods of speciation

A Szintaktikai Lokalitás Minimalista Megközelítése: A szintaktikai lokalitási feltételekért felelős nyelvi alrendszerek munkamegosztásának vizsgálata = A Minimalist Approach to Syntactic Locality: A study of the division of labour of linguistic subsystems underlying syntactic locality effects

A projekt a szintaxis és az azzal érintkező grammatikai komponensek munkamegosztását vizsgálta a mozgatási és polaritás engedélyezési függőségekben jelentkező szintaktikai lokalitási hatások területén. A projektnek a generatív grammatika mai, Minimalista kutatási programjába illeszkedő radikális tézise szerint a természetes nyelvi szintaxis egyáltalán nem is tartalmaz külön lokalitási megszorítás(oka)t. Kimutattuk, hogy az általunk vizsgált, a szintaxisban jelentkező lokalitási hatások (i) a szintaktikai komputációs rendszer általános tulajdonságaiból, különösen a komputációs komplexitása minimalizálásának igényéből, valamint (ii) a szintaxis és a vele érintkező grammatikai alrendszerek munkamegosztásából fakadnak. A projekt olyan területeken vizsgálta a lokalitási hatások természetét, mint a főnévi kifejezések által képviselt szigetek, a szintaktikai fejmozgatás, a kvantorhatókör-értelmezés, a fókuszálás, a határozói módosítás, a mondatbeágyazás, a preszuppozíciós, a tagadó és a kérdő típusú gyenge szigetek, és egyes, a polaritásengedélyezésben szerepet játszó intervenciós hatások. A több nemzetközi együttműködést is kezdeményező kutatócsoport munkájának sikerességét a számos jelentős publikáció, köztük egy sor nemzetközi folyóiratcikk és nagy presztízsű nemzetközi kiadónál megjelenő könyvfejezet is jelzi. A kutatás keretében egy megvédett DSc értekezés és egy leadott PhD disszertáció is született, és egy további doktori disszertáció készül el még ebben az évben. | This project studied the division of labour between syntax and its interface subsystems in giving rise to some of the central syntactic locality properties of dependencies like movement and polarity licensing. Implementing the current Minimalist research program of transformational generative grammar, it explored the radical proposal that natural language syntax itself includes no special syntactic locality conditions per se. Instead, the locality effects under scrutiny are reduced to (i) the elementary properties of the syntactic computational system, including its quest to keep computational complexity to a minimum, which in turn subsumes its cyclic mapping to the interpretive systems of sound and meaning; and (ii) the division of labour between syntax and the interface subsystems, in particular, semantics and information structure. The topics investigated include the locality effects involved in noun phrase islands, syntactic head movement, quantifier scope interpretation, focusing, adverbial modification, clausal embedding, weak islands like presuppositional, negative, and wh-islands, and some apparent intervention effects in polarity licensing. The project established fruitful international co-operations, and its results have appeared in the form of a number of international journal and book chapter publications. The project has also yielded a completed PhD dissertation, a PhD thesis to be submitted later this year, and a DSc dissertation

Processing presuppositions and implicatures: Similarities and differences

Presuppositions and scalar implicatures are traditionally considered to be distinct phenomena, but recent accounts analyze (at least some of) the former as the latter. All else being equal, this “scalar implicature approach to presuppositions” predicts uniform behavior for the two types of inferences. Initial experimental studies comparing them yielded conflicting results. While some found a difference in the Response Time (RT) patterns of scalar implicatures and presuppositions, others found them to be uniform. We argue that the difference in outcomes is attributable to a difference in the type of response being measured: RTs associated with acceptance and rejection responses seem to pattern in opposite ways. Next, we report on a series of experiments to support this, and to compare the behavior of the two inferences more comprehensively. Experiments Ia and Ib look at both acceptance and rejection responses for both inference types, and find uniform patterns once the acceptance vs. rejection variable is factored in. Experiment II adds a new dimension by testing for the influence of prosody on the two inference types, and in this regard a clear difference between them emerges, posing a first substantive challenge to the scalar implicature approach to presuppositions. A third set of experiments investigates yet another prediction of this approach, according to which the presuppositional inference is introduced as a simple entailment in affirmative contexts. This predicts that these presuppositional inferences behave parallel to other entailments. Experiment IIIa compares rejections of affirmative sentences based on either their presuppositional inference or their entailed content and finds that they differ, with greater RTs for the former. As an additional control, Experiments IIIb and IIIc test for parallel differences between two entailments associated with always, which yield uniform results. In sum, while Experiments Ia and Ib are in line with previous findings that presuppositions and scalar implicatures under negation show uniform response time patterns, the differences found in Experiments II and IIIa-c pose a substantial challenge to approaches assimilating the two phenomena, while being entirely in line with the traditional perspective of seeing them as distinct

Contextual blindness in implicature computation

In this paper, I defend a grammatical account of scalar implicatures. In particular, I submit new evidence in favor of the contextual blindness principle, assumed in recent versions of the grammatical account. I argue that mismatching scalar implicatures can be generated even when the restrictor of the universal quantifier in a universal alternative is contextually known to be empty. The crucial evidence consists of a hitherto unnoticed oddness asymmetry between formally analogous existential sentences with reference failure NPs. I conclude that the generation of mismatching scalar implicatures does not require contextual access

The Echinococcus canadensis (G7) genome: A key knowledge of parasitic platyhelminth human diseases

Background: The parasite Echinococcus canadensis (G7) (phylum Platyhelminthes, class Cestoda) is one of the causative agents of echinococcosis. Echinococcosis is a worldwide chronic zoonosis affecting humans as well as domestic and wild mammals, which has been reported as a prioritized neglected disease by the World Health Organisation. No genomic data, comparative genomic analyses or efficient therapeutic and diagnostic tools are available for this severe disease. The information presented in this study will help to understand the peculiar biological characters and to design species-specific control tools. Results: We sequenced, assembled and annotated the 115-Mb genome of E. canadensis (G7). Comparative genomic analyses using whole genome data of three Echinococcus species not only confirmed the status of E. canadensis (G7) as a separate species but also demonstrated a high nucleotide sequences divergence in relation to E. granulosus (G1). The E. canadensis (G7) genome contains 11,449 genes with a core set of 881 orthologs shared among five cestode species. Comparative genomics revealed that there are more single nucleotide polymorphisms (SNPs) between E. canadensis (G7) and E. granulosus (G1) than between E. canadensis (G7) and E. multilocularis. This result was unexpected since E. canadensis (G7) and E. granulosus (G1) were considered to belong to the species complex E. granulosus sensu lato. We described SNPs in known drug targets and metabolism genes in the E. canadensis (G7) genome. Regarding gene regulation, we analysed three particular features: CpG island distribution along the three Echinococcus genomes, DNA methylation system and small RNA pathway. The results suggest the occurrence of yet unknown gene regulation mechanisms in Echinococcus. Conclusions: This is the first work that addresses Echinococcus comparative genomics. The resources presented here will promote the study of mechanisms of parasite development as well as new tools for drug discovery. The availability of a high-quality genome assembly is critical for fully exploring the biology of a pathogenic organism. The E. canadensis (G7) genome presented in this study provides a unique opportunity to address the genetic diversity among the genus Echinococcus and its particular developmental features. At present, there is no unequivocal taxonomic classification of Echinococcus species; however, the genome-wide SNPs analysis performed here revealed the phylogenetic distance among these three Echinococcus species. Additional cestode genomes need to be sequenced to be able to resolve their phylogeny.Fil: Maldonado, Lucas Luciano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Assis, Juliana. Fundación Oswaldo Cruz; BrasilFil: Gomes Araújo, Flávio M.. Fundación Oswaldo Cruz; BrasilFil: Salim, Anna C. M.. Fundación Oswaldo Cruz; BrasilFil: Macchiaroli, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Cucher, Marcela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Camicia, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Fox, Adolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Rosenzvit, Mara Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Oliveira, Guilherme. Instituto Tecnológico Vale; Brasil. Fundación Oswaldo Cruz; BrasilFil: Kamenetzky, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentin