Spliceosomal introns as tools for genomic and evolutionary analysis

Over the past 5 years, the availability of dozens of whole genomic sequences from a wide variety of eukaryotic lineages has revealed a very large amount of information about the dynamics of intron loss and gain through eukaryotic history, as well as the evolution of intron sequences. Implicit in these advances is a great deal of information about the structure and evolution of surrounding sequences. Here, we review the wealth of ways in which structures of spliceosomal introns as well as their conservation and change through evolution may be harnessed for evolutionary and genomic analysis. First, we discuss uses of intron length distributions and positions in sequence assembly and annotation, and for improving alignment of homologous regions. Second, we review uses of introns in evolutionary studies, including the utility of introns as indicators of rates of sequence evolution, for inferences about molecular evolution, as signatures of orthology and paralogy, and for estimating rates of nucleotide substitution. We conclude with a discussion of phylogenetic methods utilizing intron sequences and positions

Functional and evolutionary analysis of alternatively spliced genes is consistent with an early eukaryotic origin of alternative splicing

<p>Abstract</p> <p>Background</p> <p>Alternative splicing has been reported in various eukaryotic groups including plants, apicomplexans, diatoms, amoebae, animals and fungi. However, whether widespread alternative splicing has evolved independently in the different eukaryotic groups or was inherited from their last common ancestor, and may therefore predate multicellularity, is still unknown. To better understand the origin and evolution of alternative splicing and its usage in diverse organisms, we studied alternative splicing in 12 eukaryotic species, comparing rates of alternative splicing across genes of different functional classes, cellular locations, intron/exon structures and evolutionary origins.</p> <p>Results</p> <p>For each species, we find that genes from most functional categories are alternatively spliced. Ancient genes (shared between animals, fungi and plants) show high levels of alternative splicing. Genes with products expressed in the nucleus or plasma membrane are generally more alternatively spliced while those expressed in extracellular location show less alternative splicing. We find a clear correspondence between incidence of alternative splicing and intron number per gene both within and between genomes. In general, we find several similarities in patterns of alternative splicing across these diverse eukaryotes.</p> <p>Conclusion</p> <p>Along with previous studies indicating intron-rich genes with weak intron boundary consensus and complex spliceosomes in ancestral organisms, our results suggest that at least a simple form of alternative splicing may already have been present in the unicellular ancestor of plants, fungi and animals. A role for alternative splicing in the evolution of multicellularity then would largely have arisen by co-opting the preexisting process.</p

Panoramic and tomographic implant studies : role in the diagnosis of sinus disorders

Objective: To study the presence of sinus disorders and their diagnosis based on clinical and radiographic findings, correlating their presence with tomography tests and panoramic radiography. Study design: We conducted a retrospective study on 152 patients who were seeking implant treatment, thereby allowing us to evaluate 42 patients who had abnormal sinuses. The patients underwent an evaluation of their medical history as well a clinical examination, panoramic radiography and tomographic study. Results: The average age of the patient was 59.8 years old, and 54.76% of the group were males and 45.23% were females. Prior respiratory disorders were present in 52.38% of the patients, and 57.3% of the group presented dental disorders. In assessing the type of wound, we observed that 73.21% were mucosal hyperplasia and 26.78% were mucous cysts. Of the 56 sinuses affected, only 28.57% were diagnosed using panoramic radiography. Conclusions: Panoramic radiography has limitations in the diagnosis of sinus disorders; computerized tomography (CT) remains the most effective diagnostic test

Conserved developmental expression of Fezf in chordates and Drosophila and the origin of the Zona Limitans Intrathalamica (ZLI) brain organizer

Background: The zona limitans intrathalamica (ZLI) and the isthmus organizer (IsO) are two major secondary organizers of vertebrate brain development. These organizers are located at the interface of the expression domains of key patterning genes (Fezf-Irx and Otx-Gbx, respectively). To gain insights into the evolutionary origin of the ZLI, we studied Fezf in bilaterians. Results: In this paper, we identified a conserved sequence motif (Fezf box) in all bilaterians. We report the expression pattern of Fezf in amphioxus and Drosophila and compare it with those of Gbx, Otx and Irx. We found that the relative expression patterns of these genes in vertebrates are fully conserved in amphioxus and flies, indicating that the genetic subdivisions defining the location of both secondary organizers in early vertebrate brain development were probably present in the last common ancestor of extant bilaterians. However, in contrast to vertebrates, we found that Irx-defective flies do not show an affected Fezf expression pattern. Conclusions: The absence of expression of the corresponding morphogens from cells at these conserved genetic boundaries in invertebrates suggests that the organizing properties might have evolved specifically in the vertebrate lineage by the recruitment of key morphogens to these conserved genetic locations

Comparative genomics of the Hedgehog loci in chordates and the origins of Shh regulatory novelties

The origin and evolution of the complex regulatory landscapes of some vertebrate developmental genes, often spanning hundreds of Kbp and including neighboring genes, remain poorly understood. The Sonic Hedgehog (Shh) genomic regulatory block (GRB) is one of the best functionally characterized examples, with several discrete enhancers reported within its introns, vast upstream gene-free region and neighboring genes (Lmbr1 and Rnf32). To investigate the origin and evolution of this GRB, we sequenced and characterized the Hedgehog (Hh) loci from three invertebrate chordate amphioxus species, which share several early expression domains with Shh. Using phylogenetic footprinting within and between chordate lineages, and reporter assays in zebrafish probing >30 Kbp of amphioxus Hh, we report large sequence and functional divergence between both groups. In addition, we show that the linkage of Shh to Lmbr1 and Rnf32, necessary for the unique gnatostomate-specific Shh limb expression, is a vertebrate novelty occurred between the two whole-genome duplications

Parallel evolution of a splicing program controlling neuronal excitability in flies and mammals

Alternative splicing increases neuronal transcriptomic complexity throughout animal phylogeny. To delve into the mechanisms controlling the assembly and evolution of this regulatory layer, we characterized the neuronal microexon program in Drosophila and compared it with that of mammals. In nonvertebrate bilaterians, this splicing program is restricted to neurons by the posttranscriptional processing of the enhancer of microexons (eMIC) domain in Srrm234. In Drosophila, this processing is dependent on regulation by Elav/Fne. eMIC deficiency or misexpression leads to widespread neurological alterations largely emerging from impaired neuronal activity, as revealed by a combination of neuronal imaging experiments and cell type–specific rescues. These defects are associated with the genome-wide skipping of short neural exons, which are strongly enriched in ion channels. We found no overlap of eMIC-regulated exons between flies and mice, illustrating how ancient posttranscriptional programs can evolve independently in different phyla to affect distinct cellular modules while maintaining cell-type specificity

Complex selection on 5' splice sites in intron-rich organisms

In contrast to the typically streamlined genomes of prokaryotes, many eukaryotic genomes are riddled with long intergenic regions, spliceosomal introns, and repetitive elements. What explains the persistence of these and other seemingly suboptimal structures? There are three general hypotheses: (1) the structures in question are not actually suboptimal but optimal, being favored by selection, for unknown reasons; (2) the structures are not suboptimal, but of (essentially) equal fitness to 'optimal' ones; or (3) the structures are truly suboptimal, but selection is too weak to systematically eliminate them. The 5' splice sites of introns offer a rare opportunity to directly test these hypotheses. Intron-poor species show a clear consensus splice site; most introns begin with the same six nucleotide sequence (typically GTAAGT or GTATGT), indicating efficient selection for this consensus sequence. In contrast, intron-rich species have much less pronounced boundary consensus sequences, and only small minorities of introns in intron-rich species share the same boundary sequence. We studied rates of evolutionary change of 5' splice sites in three groups of closely related intron-rich species--three primates, five Drosophila species, and four Cryptococcus fungi. Surprisingly, the results indicate that changes from consensus-to-variant nucleotides are generally disfavored by selection, but that changes from variant to consensus are neither favored nor disfavored. This evolutionary pattern is consistent with selective differences across introns, for instance, due to compensatory changes at other sites within the gene, which compensate for the otherwise suboptimal consensus-to-variant changes in splice boundaries

Experiencias docentes en la asignatura de Dirección Financiera impartida en inglés

En las líneas que siguen hemos querido reflejar sucintamente nuestra experiencia de tres cursos académicos en la enseñanza en lengua inglesa de la asignatura de Dirección Financiera (Financial Management). Sin renunciar al rigor expositivo, hemos optado por contar de forma directa las dificultades surgidas, las estrategias docentes adoptadas y también las oportunidades que pensamos ofrece la enseñanza en lengua inglesa. Más que las disquisiciones teóricas —valiosas sin duda—, lo que podemos ofrecer son vivencias reales que, junto con las de otros docentes, puedan servir para el análisis y el debate que conduzcan a la mejora de dicha enseñanza

Widespread intron retention in mammals functionally tunes transcriptomes

© 2014 Braunschweig et al.; Published by Cold Spring Harbor Laboratory Press. This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.Alternative splicing (AS) of precursor RNAs is responsible for greatly expanding the regulatory and functional capacity of eukaryotic genomes. Of the different classes of AS, intron retention (IR) is the least well understood. In plants and unicellular eukaryotes, IR is the most common form of AS, whereas in animals, it is thought to represent the least prevalent form. Using high-coverage poly(A)(+) RNA-seq data, we observe that IR is surprisingly frequent in mammals, affecting transcripts from as many as three-quarters of multiexonic genes. A highly correlated set of cis features comprising an "IR code" reliably discriminates retained from constitutively spliced introns. We show that IR acts widely to reduce the levels of transcripts that are less or not required for the physiology of the cell or tissue type in which they are detected. This "transcriptome tuning" function of IR acts through both nonsense-mediated mRNA decay and nuclear sequestration and turnover of IR transcripts. We further show that IR is linked to a cross-talk mechanism involving localized stalling of RNA polymerase II (Pol II) and reduced availability of spliceosomal components. Collectively, the results implicate a global checkpoint-type mechanism whereby reduced recruitment of splicing components coupled to Pol II pausing underlies widespread IR-mediated suppression of inappropriately expressed transcripts.This work was supported by grants from the Canadian Institutes of Health Research and Canadian Cancer Society (B.J.B.); EMBO long-term fellowships (U.B. and T.G.-P.); Human Frontier Science Program Organization long-term fellowships (U.B. and M.I.); an OSCI fellowship (T.G.-P.); CIHR postdoctoral and Marie Curie IOF fellowships (N.L.B.-M.); and an NSERC studentship (E.N.).info:eu-repo/semantics/publishedVersio