Publications by authors named "André Corvelo"

25 Publications

  • Page 1 of 1

Molecular Phylogeny and Evolution of Amazon Parrots in the Greater Antilles.

Genes (Basel) 2021 Apr 20;12(4). Epub 2021 Apr 20.

Biology Department, University of Puerto Rico at Mayagüez, Mayagüez 00682, Puerto Rico.

Amazon parrots ( spp.) colonized the islands of the Greater Antilles from the Central American mainland, but there has not been a consensus as to how and when this happened. Today, most of the five remaining island species are listed as endangered, threatened, or vulnerable as a consequence of human activity. We sequenced and annotated full mitochondrial genomes of all the extant Amazon parrot species from the Greater Antillean ( (Cuba), , (both from Jamaica), (Hispaniola), and (Puerto Rico)), from mainland Central America, and from the Atlantic Forest in Brazil. The assembled and annotated mitogenome maps provide information on sequence organization, variation, population diversity, and evolutionary history for the Caribbean species including the critically endangered . Despite the larger number of available samples from the Puerto Rican Parrot Recovery Program, the sequence diversity of the population in Puerto Rico was the lowest among all parrot species analyzed. Our data support the stepping-stone dispersal and speciation hypothesis that has started approximately 3.47 MYA when the ancestral population arrived from mainland Central America and led to diversification across the Greater Antilles, ultimately reaching the island of Puerto Rico 0.67 MYA. The results are presented and discussed in light of the geological history of the Caribbean and in the context of recent parrot evolution, island biogeography, and conservation. This analysis contributes to understating evolutionary history and empowers subsequent assessments of sequence variation and helps design future conservation efforts in the Caribbean.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/genes12040608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074781PMC
April 2021

Feather Gene Expression Elucidates the Developmental Basis of Plumage Iridescence in African Starlings.

J Hered 2021 Apr 22. Epub 2021 Apr 22.

Department of Ecology, Evolution and Environmental Biology, Columbia University, New York, NY.

Iridescence is widespread in the living world, occurring in organisms as diverse as bacteria, plants, and animals. Yet, compared to pigment-based forms of coloration, we know surprisingly little about the developmental and molecular bases of the structural colors that give rise to iridescence. Birds display a rich diversity of iridescent structural colors that are produced in feathers by the arrangement of melanin-containing organelles called melanosomes into nanoscale configurations, but how these often unusually shaped melanosomes form, or how they are arranged into highly organized nanostructures, remains largely unknown. Here, we use functional genomics to explore the developmental basis of iridescent plumage using superb starlings (Lamprotornis superbus), which produce both iridescent blue and non-iridescent red feathers. Through morphological and chemical analyses, we confirm that hollow, flattened melanosomes in iridescent feathers are eumelanin-based, whereas melanosomes in non-iridescent feathers are solid and amorphous, suggesting that high pheomelanin content underlies red coloration. Intriguingly, the nanoscale arrangement of melanosomes within the barbules was surprisingly similar between feather types. After creating a new genome assembly, we use transcriptomics to show that non-iridescent feather development is associated with genes related to pigmentation, metabolism, and mitochondrial function, suggesting non-iridescent feathers are more energetically expensive to produce than iridescent feathers. However, iridescent feather development is associated with genes related to structural and cellular organization, suggesting that, while nanostructures themselves may passively assemble, barbules and melanosomes may require active organization to give them their shape. Together, our analyses suggest that iridescent feathers form through a combination of passive self-assembly and active processes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jhered/esab014DOI Listing
April 2021

Systemic Tissue and Cellular Disruption from SARS-CoV-2 Infection revealed in COVID-19 Autopsies and Spatial Omics Tissue Maps.

bioRxiv 2021 Mar 9. Epub 2021 Mar 9.

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus has infected over 115 million people and caused over 2.5 million deaths worldwide. Yet, the molecular mechanisms underlying the clinical manifestations of COVID-19, as well as what distinguishes them from common seasonal influenza virus and other lung injury states such as Acute Respiratory Distress Syndrome (ARDS), remains poorly understood. To address these challenges, we combined transcriptional profiling of 646 clinical nasopharyngeal swabs and 39 patient autopsy tissues, matched with spatial protein and expression profiling (GeoMx) across 357 tissue sections. These results define both body-wide and tissue-specific (heart, liver, lung, kidney, and lymph nodes) damage wrought by the SARS-CoV-2 infection, evident as a function of varying viral load (high vs. low) during the course of infection and specific, transcriptional dysregulation in splicing isoforms, T cell receptor expression, and cellular expression states. In particular, cardiac and lung tissues revealed the largest degree of splicing isoform switching and cell expression state loss. Overall, these findings reveal a systemic disruption of cellular and transcriptional pathways from COVID-19 across all tissues, which can inform subsequent studies to combat the mortality of COVID-19, as well to better understand the molecular dynamics of lethal SARS-CoV-2 infection and other viruses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1101/2021.03.08.434433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987017PMC
March 2021

Haplotype-resolved diverse human genomes and integrated analysis of structural variation.

Science 2021 04 25;372(6537). Epub 2021 Feb 25.

New York Genome Center, New York, NY 10013, USA.

Long-read and strand-specific sequencing technologies together facilitate the de novo assembly of high-quality haplotype-resolved human genomes without parent-child trio data. We present 64 assembled haplotypes from 32 diverse human genomes. These highly contiguous haplotype assemblies (average minimum contig length needed to cover 50% of the genome: 26 million base pairs) integrate all forms of genetic variation, even across complex loci. We identified 107,590 structural variants (SVs), of which 68% were not discovered with short-read sequencing, and 278 SV hotspots (spanning megabases of gene-rich sequence). We characterized 130 of the most active mobile element source elements and found that 63% of all SVs arise through homology-mediated mechanisms. This resource enables reliable graph-based genotyping from short reads of up to 50,340 SVs, resulting in the identification of 1526 expression quantitative trait loci as well as SV candidates for adaptive selection within the human population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/science.abf7117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026704PMC
April 2021

Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program.

Nature 2021 02 10;590(7845):290-299. Epub 2021 Feb 10.

The Broad Institute of MIT and Harvard, Cambridge, MA, USA.

The Trans-Omics for Precision Medicine (TOPMed) programme seeks to elucidate the genetic architecture and biology of heart, lung, blood and sleep disorders, with the ultimate goal of improving diagnosis, treatment and prevention of these diseases. The initial phases of the programme focused on whole-genome sequencing of individuals with rich phenotypic data and diverse backgrounds. Here we describe the TOPMed goals and design as well as the available resources and early insights obtained from the sequence data. The resources include a variant browser, a genotype imputation server, and genomic and phenotypic data that are available through dbGaP (Database of Genotypes and Phenotypes). In the first 53,831 TOPMed samples, we detected more than 400 million single-nucleotide and insertion or deletion variants after alignment with the reference genome. Additional previously undescribed variants were detected through assembly of unmapped reads and customized analysis in highly variable loci. Among the more than 400 million detected variants, 97% have frequencies of less than 1% and 46% are singletons that are present in only one individual (53% among unrelated individuals). These rare variants provide insights into mutational processes and recent human evolutionary history. The extensive catalogue of genetic variation in TOPMed studies provides unique opportunities for exploring the contributions of rare and noncoding sequence variants to phenotypic variation. Furthermore, combining TOPMed haplotypes with modern imputation methods improves the power and reach of genome-wide association studies to include variants down to a frequency of approximately 0.01%.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41586-021-03205-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875770PMC
February 2021

Reduced Motivation in Perinatal Fluoxetine-Treated Mice: A Hypodopaminergic Phenotype.

J Neurosci 2021 Mar 3;41(12):2723-2732. Epub 2021 Feb 3.

Emotional Brain Institute, Nathan Kline Institute for Psychiatric Research, Orangeburg, New York 10962

Early life is a sensitive period, in which enhanced neural plasticity allows the developing brain to adapt to its environment. This plasticity can also be a risk factor in which maladaptive development can lead to long-lasting behavioral deficits. Here, we test how early-life exposure to the selective-serotonin-reuptake-inhibitor (SSRI), fluoxetine, affects motivation, and dopaminergic signaling in adulthood. We show for the first time that mice exposed to fluoxetine in the early postnatal period exhibit a reduction in effort-related motivation. These mice also show blunted responses to amphetamine and reduced dopaminergic activation in a sucrose reward task. Interestingly, we find that the reduction in motivation can be rescued in the adult by administering bupropion, a dopamine-norepinephrine reuptake inhibitor used as an antidepressant and a smoke cessation aid but not by fluoxetine. Taken together, our studies highlight the effects of early postnatal exposure of fluoxetine on motivation and demonstrate the involvement of the dopaminergic system in this process. The developmental period is characterized by enhanced plasticity. During this period, environmental factors have the potential to lead to enduring behavioral changes. Here, we show that exposure to the SSRI fluoxetine during a restricted period in early life leads to a reduction in adult motivation. We further show that this reduction is associated with decreased dopaminergic responsivity. Finally, we show that motivational deficits induced by early-life fluoxetine exposure can be rescued by adult administration of bupropion but not by fluoxetine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1523/JNEUROSCI.2608-20.2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018732PMC
March 2021

Somatic variant analysis of linked-reads sequencing data with Lancet.

Bioinformatics 2020 Oct 17. Epub 2020 Oct 17.

Computational Biology Lab, New York Genome Center, New York, NY 10013, USA.

Summary: We present a new version of the popular somatic variant caller, Lancet, that supports the analysis of linked-reads sequencing data. By seamlessly integrating barcodes and haplotype read assignments within the colored De Bruijn graph local-assembly framework, Lancet computes a barcode-aware coverage and identifies variants that disagree with the local haplotype structure.

Availability And Implementation: Lancet is implemented in C++ and available for academic and non-commercial research purposes as an open-source package at https://github.com/nygenome/lancet.

Supplementary Information: Supplementary data are available at Bioinformatics online.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/bioinformatics/btaa888DOI Listing
October 2020

Dense sampling of bird diversity increases power of comparative genomics.

Nature 2020 11 11;587(7833):252-257. Epub 2020 Nov 11.

Centre for Zoo and Wild Animal Health, Copenhagen Zoo, Frederiksberg, Denmark.

Whole-genome sequencing projects are increasingly populating the tree of life and characterizing biodiversity. Sparse taxon sampling has previously been proposed to confound phylogenetic inference, and captures only a fraction of the genomic diversity. Here we report a substantial step towards the dense representation of avian phylogenetic and molecular diversity, by analysing 363 genomes from 92.4% of bird families-including 267 newly sequenced genomes produced for phase II of the Bird 10,000 Genomes (B10K) Project. We use this comparative genome dataset in combination with a pipeline that leverages a reference-free whole-genome alignment to identify orthologous regions in greater numbers than has previously been possible and to recognize genomic novelties in particular bird lineages. The densely sampled alignment provides a single-base-pair map of selection, has more than doubled the fraction of bases that are confidently predicted to be under conservation and reveals extensive patterns of weak selection in predominantly non-coding DNA. Our results demonstrate that increasing the diversity of genomes used in comparative studies can reveal more shared and lineage-specific variation, and improve the investigation of genomic characteristics. We anticipate that this genomic resource will offer new perspectives on evolutionary processes in cross-species comparative analyses and assist in efforts to conserve species.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41586-020-2873-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759463PMC
November 2020

Massive gene presence-absence variation shapes an open pan-genome in the Mediterranean mussel.

Genome Biol 2020 11 10;21(1):275. Epub 2020 Nov 10.

Instituto de Investigaciones Marinas (IIM - CSIC), Eduardo Cabello, 6, 36208, Vigo, Spain.

Background: The Mediterranean mussel Mytilus galloprovincialis is an ecologically and economically relevant edible marine bivalve, highly invasive and resilient to biotic and abiotic stressors causing recurrent massive mortalities in other bivalves. Although these traits have been recently linked with the maintenance of a high genetic variation within natural populations, the factors underlying the evolutionary success of this species remain unclear.

Results: Here, after the assembly of a 1.28-Gb reference genome and the resequencing of 14 individuals from two independent populations, we reveal a complex pan-genomic architecture in M. galloprovincialis, with a core set of 45,000 genes plus a strikingly high number of dispensable genes (20,000) subject to presence-absence variation, which may be entirely missing in several individuals. We show that dispensable genes are associated with hemizygous genomic regions affected by structural variants, which overall account for nearly 580 Mb of DNA sequence not included in the reference genome assembly. As such, this is the first study to report the widespread occurrence of gene presence-absence variation at a whole-genome scale in the animal kingdom.

Conclusions: Dispensable genes usually belong to young and recently expanded gene families enriched in survival functions, which might be the key to explain the resilience and invasiveness of this species. This unique pan-genome architecture is characterized by dispensable genes in accessory genomic regions that exceed by orders of magnitude those observed in other metazoans, including humans, and closely mirror the open pan-genomes found in prokaryotes and in a few non-metazoan eukaryotes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13059-020-02180-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653742PMC
November 2020

Targeted Knockout of β-Catenin in Adult Melanocyte Stem Cells Using a Mouse Line, Dct::CreER, Results in Disrupted Stem Cell Renewal and Pigmentation Defects.

J Invest Dermatol 2021 May 20;141(5):1363-1366.e9. Epub 2020 Oct 20.

INSERM U1021, Normal and Pathological Development of Melanocytes, Institut Curie, PSL Research University, Orsay, France; CNRS UMR3347, Paris-Sud University, University Paris-Saclay, Paris, France; Equipe Labellisée, Ligue Contre le Cancer, Paris, France. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jid.2020.08.025DOI Listing
May 2021

Adaptive Radiation Genomics of Two Ecologically Divergent Hawai'ian Honeycreepers: The 'akiapōlā'au and the Hawai'i 'amakihi.

J Hered 2020 02;111(1):21-32

Center for Conservation Genomics, Smithsonian National Zoo and Conservation Biology Institute, Washington, DC.

The Hawai'ian honeycreepers (drepanids) are a classic example of adaptive radiation: they adapted to a variety of novel dietary niches, evolving a wide range of bill morphologies. Here we investigated genomic diversity, demographic history, and genes involved in bill morphology phenotypes in 2 honeycreepers: the 'akiapōlā'au (Hemignathus wilsoni) and the Hawai'i 'amakihi (Chlorodrepanis virens). The 'akiapōlā'au is an endangered island endemic, filling the "woodpecker" niche by using a unique bill morphology, while the Hawai'i 'amakihi is a dietary generalist common on the islands of Hawai'i and Maui. We de novo sequenced the 'akiapōlā'au genome and compared it to the previously sequenced 'amakihi genome. The 'akiapōlā'au is far less heterozygous and has a smaller effective population size than the 'amakihi, which matches expectations due to its smaller census population and restricted ecological niche. Our investigation revealed genomic islands of divergence, which may be involved in the honeycreeper radiation. Within these islands of divergence, we identified candidate genes (including DLK1, FOXB1, KIF6, MAML3, PHF20, RBP1, and TIMM17A) that may play a role in honeycreeper adaptations. The gene DLK1, previously shown to influence Darwin's finch bill size, may be related to honeycreeper bill morphology evolution, while the functions of the other candidates remain unknown.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jhered/esz057DOI Listing
February 2020

Phylogenomics Identifies an Ancestral Burst of Gene Duplications Predating the Diversification of Aphidomorpha.

Mol Biol Evol 2020 03;37(3):730-756

Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain.

Aphids (Aphidoidea) are a diverse group of hemipteran insects that feed on plant phloem sap. A common finding in studies of aphid genomes is the presence of a large number of duplicated genes. However, when these duplications occurred remains unclear, partly due to the high relatedness of sequenced species. To better understand the origin of aphid duplications we sequenced and assembled the genome of Cinara cedri, an early branching lineage (Lachninae) of the Aphididae family. We performed a phylogenomic comparison of this genome with 20 other sequenced genomes, including the available genomes of five other aphids, along with the transcriptomes of two species belonging to Adelgidae (a closely related clade to the aphids) and Coccoidea. We found that gene duplication has been pervasive throughout the evolution of aphids, including many parallel waves of recent, species-specific duplications. Most notably, we identified a consistent set of very ancestral duplications, originating from a large-scale gene duplication predating the diversification of Aphidomorpha (comprising aphids, phylloxerids, and adelgids). Genes duplicated in this ancestral wave are enriched in functions related to traits shared by Aphidomorpha, such as association with endosymbionts, and adaptation to plant defenses and phloem-sap-based diet. The ancestral nature of this duplication wave (106-227 Ma) and the lack of sufficiently conserved synteny make it difficult to conclude whether it originated from a whole-genome duplication event or, alternatively, from a burst of large-scale segmental duplications. Genome sequencing of other aphid species belonging to different Aphidomorpha and related lineages may clarify these findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/molbev/msz261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7038657PMC
March 2020

Sequencing two Tyr::CreER transgenic mouse lines.

Pigment Cell Melanoma Res 2020 05 19;33(3):426-434. Epub 2019 Nov 19.

Institut Curie, INSERM U1021, Normal and Pathological Development of Melanocytes, PSL Research University, Orsay, France.

The Cre/loxP system is a powerful tool that has allowed the study of the effects of specific genes of interest in various biological settings. The Tyr::CreER system allows for the targeted expression and activity of the Cre enzyme in the melanocyte lineage following treatment with tamoxifen, thus providing spatial and temporal control of the expression of specific target genes. Two independent transgenic mouse models, each containing a Tyr::CreER transgene, have been generated and are widely used to study melanocyte transformation. In this study, we performed whole genome sequencing (WGS) on genomic DNA from the two Tyr::CreER mouse models and identified their sites of integration in the C57BL/6 genome. Based on these results, we designed PCR primers to accurately, and efficiently, genotype transgenic mice. Finally, we discussed some of the advantages of each transgenic mouse model.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/pcmr.12842DOI Listing
May 2020

Genome-wide somatic variant calling using localized colored de Bruijn graphs.

Commun Biol 2018 22;1:20. Epub 2018 Mar 22.

New York Genome Center, New York, NY, 10013, USA.

Reliable detection of somatic variations is of critical importance in cancer research. Here we present Lancet, an accurate and sensitive somatic variant caller, which detects SNVs and indels by jointly analyzing reads from tumor and matched normal samples using colored de Bruijn graphs. We demonstrate, through extensive experimental comparison on synthetic and real whole-genome sequencing datasets, that Lancet has better accuracy, especially for indel detection, than widely used somatic callers, such as MuTect, MuTect2, LoFreq, Strelka, and Strelka2. Lancet features a reliable variant scoring system, which is essential for variant prioritization, and detects low-frequency mutations without sacrificing the sensitivity to call longer insertions and deletions empowered by the local-assembly engine. In addition to genome-wide analysis, Lancet allows inspection of somatic variants in graph space, which augments the traditional read alignment visualization to help confirm a variant of interest. Lancet is available as an open-source program at https://github.com/nygenome/lancet.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s42003-018-0023-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6123722PMC
March 2018

taxMaps: comprehensive and highly accurate taxonomic classification of short-read data in reasonable time.

Genome Res 2018 05 27;28(5):751-758. Epub 2018 Mar 27.

New York Genome Center, New York, New York 10013, USA.

High-throughput sequencing is a revolutionary technology for the analysis of metagenomic samples. However, querying large volumes of reads against comprehensive DNA/RNA databases in a sensitive manner can be compute-intensive. Here, we present taxMaps, a highly efficient, sensitive, and fully scalable taxonomic classification tool. Using a combination of simulated and real metagenomics data sets, we demonstrate that taxMaps is more sensitive and more precise than widely used taxonomic classifiers and is capable of delivering classification accuracy comparable to that of BLASTN, but at up to three orders of magnitude less computational cost.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1101/gr.225276.117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5932614PMC
May 2018

Speciation over the edge: gene flow among non-human primate species across a formidable biogeographic barrier.

R Soc Open Sci 2017 Oct 18;4(10):170351. Epub 2017 Oct 18.

Department of Ecology, Evolution, and Environmental Biology, Columbia University, 10th floor Schermerhorn Extension, 119th Street and Amsterdam Avenue, New York, NY 10027, USA.

Many genera of terrestrial vertebrates diversified exclusively on one or the other side of Wallace's Line, which lies between Borneo and Sulawesi islands in Southeast Asia, and demarcates one of the sharpest biogeographic transition zones in the world. Macaque monkeys are unusual among vertebrate genera in that they are distributed on both sides of Wallace's Line, raising the question of whether dispersal across this barrier was an evolutionary one-off or a more protracted exchange-and if the latter, what were the genomic consequences. To explore the nature of speciation over the edge of this biogeographic divide, we used genomic data to test for evidence of gene flow between macaque species across Wallace's Line after macaques colonized Sulawesi. We recovered evidence of post-colonization gene flow, most prominently on the X chromosome. These results are consistent with the proposal that gene flow is a pervasive component of speciation-even when barriers to gene flow seem almost insurmountable.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1098/rsos.170351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5666242PMC
October 2017

Extreme genomic erosion after recurrent demographic bottlenecks in the highly endangered Iberian lynx.

Genome Biol 2016 12 14;17(1):251. Epub 2016 Dec 14.

CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 4, 08028, Barcelona, Spain.

Background: Genomic studies of endangered species provide insights into their evolution and demographic history, reveal patterns of genomic erosion that might limit their viability, and offer tools for their effective conservation. The Iberian lynx (Lynx pardinus) is the most endangered felid and a unique example of a species on the brink of extinction.

Results: We generate the first annotated draft of the Iberian lynx genome and carry out genome-based analyses of lynx demography, evolution, and population genetics. We identify a series of severe population bottlenecks in the history of the Iberian lynx that predate its known demographic decline during the 20th century and have greatly impacted its genome evolution. We observe drastically reduced rates of weak-to-strong substitutions associated with GC-biased gene conversion and increased rates of fixation of transposable elements. We also find multiple signatures of genetic erosion in the two remnant Iberian lynx populations, including a high frequency of potentially deleterious variants and substitutions, as well as the lowest genome-wide genetic diversity reported so far in any species.

Conclusions: The genomic features observed in the Iberian lynx genome may hamper short- and long-term viability through reduced fitness and adaptive potential. The knowledge and resources developed in this study will boost the research on felid evolution and conservation genomics and will benefit the ongoing conservation and management of this emblematic species.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13059-016-1090-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5155386PMC
December 2016

Characterization of a Novel Orthomyxo-like Virus Causing Mass Die-Offs of Tilapia.

mBio 2016 Apr 5;7(2):e00431-16. Epub 2016 Apr 5.

Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, New York, USA

Unlabelled: Tilapia are an important global food source due to their omnivorous diet, tolerance for high-density aquaculture, and relative disease resistance. Since 2009, tilapia aquaculture has been threatened by mass die-offs in farmed fish in Israel and Ecuador. Here we report evidence implicating a novel orthomyxo-like virus in these outbreaks. The tilapia lake virus (TiLV) has a 10-segment, negative-sense RNA genome. The largest segment, segment 1, contains an open reading frame with weak sequence homology to the influenza C virus PB1 subunit. The other nine segments showed no homology to other viruses but have conserved, complementary sequences at their 5' and 3' termini, consistent with the genome organization found in other orthomyxoviruses. In situ hybridization indicates TiLV replication and transcription at sites of pathology in the liver and central nervous system of tilapia with disease.

Importance: The economic impact of worldwide trade in tilapia is estimated at $7.5 billion U.S. dollars (USD) annually. The infectious agent implicated in mass tilapia die-offs in two continents poses a threat to the global tilapia industry, which not only provides inexpensive dietary protein but also is a major employer in the developing world. Here we report characterization of the causative agent as a novel orthomyxo-like virus, tilapia lake virus (TiLV). We also describe complete genomic and protein sequences that will facilitate TiLV detection and containment and enable vaccine development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/mBio.00431-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4959514PMC
April 2016

Whole genome sequencing of turbot (Scophthalmus maximus; Pleuronectiformes): a fish adapted to demersal life.

DNA Res 2016 Jun 6;23(3):181-92. Epub 2016 Mar 6.

Centre Nacional d'Anàlisi Genòmica (CNAG-CRG), Centre de Regulació Genómica, Parc Científic de Barcelona, Barcelona 08028, Spain.

The turbot is a flatfish (Pleuronectiformes) with increasing commercial value, which has prompted active genomic research aimed at more efficient selection. Here we present the sequence and annotation of the turbot genome, which represents a milestone for both boosting breeding programmes and ascertaining the origin and diversification of flatfish. We compare the turbot genome with model fish genomes to investigate teleost chromosome evolution. We observe a conserved macrosyntenic pattern within Percomorpha and identify large syntenic blocks within the turbot genome related to the teleost genome duplication. We identify gene family expansions and positive selection of genes associated with vision and metabolism of membrane lipids, which suggests adaptation to demersal lifestyle and to cold temperatures, respectively. Our data indicate a quick evolution and diversification of flatfish to adapt to benthic life and provide clues for understanding their controversial origin. Moreover, we investigate the genomic architecture of growth, sex determination and disease resistance, key traits for understanding local adaptation and boosting turbot production, by mapping candidate genes and previously reported quantitative trait loci. The genomic architecture of these productive traits has allowed the identification of candidate genes and enriched pathways that may represent useful information for future marker-assisted selection in turbot.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/dnares/dsw007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4909306PMC
June 2016

Genome and transcriptome analysis of the Mesoamerican common bean and the role of gene duplications in establishing tissue and temporal specialization of genes.

Genome Biol 2016 Feb 25;17:32. Epub 2016 Feb 25.

Environmental Biology Department, Centro de Investigaciones Biológicas, (CSIC), 28040, Madrid, Spain.

Background: Legumes are the third largest family of angiosperms and the second most important crop class. Legume genomes have been shaped by extensive large-scale gene duplications, including an approximately 58 million year old whole genome duplication shared by most crop legumes.

Results: We report the genome and the transcription atlas of coding and non-coding genes of a Mesoamerican genotype of common bean (Phaseolus vulgaris L., BAT93). Using a comprehensive phylogenomics analysis, we assessed the past and recent evolution of common bean, and traced the diversification of patterns of gene expression following duplication. We find that successive rounds of gene duplications in legumes have shaped tissue and developmental expression, leading to increased levels of specialization in larger gene families. We also find that many long non-coding RNAs are preferentially expressed in germ-line-related tissues (pods and seeds), suggesting that they play a significant role in fruit development. Our results also suggest that most bean-specific gene family expansions, including resistance gene clusters, predate the split of the Mesoamerican and Andean gene pools.

Conclusions: The genome and transcriptome data herein generated for a Mesoamerican genotype represent a counterpart to the genomic resources already available for the Andean gene pool. Altogether, this information will allow the genetic dissection of the characters involved in the domestication and adaptation of the crop, and their further implementation in breeding strategies for this important crop.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13059-016-0883-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4766624PMC
February 2016

Overexpression of Reelin prevents the manifestation of behavioral phenotypes related to schizophrenia and bipolar disorder.

Neuropsychopharmacology 2011 Nov 3;36(12):2395-405. Epub 2011 Aug 3.

Developmental Neurobiology and Regeneration Unit, Institute for Research in Biomedicine, Parc Cientific de Barcelona, University of Barcelona, Barcelona, Spain.

Despite the impact of schizophrenia and mood disorders, which in extreme cases can lead to death, recent decades have brought little progress in the development of new treatments. Recent studies have shown that Reelin, an extracellular protein that is critical for neuronal development, is reduced in schizophrenia and bipolar disorder patients. However, data on a causal or protective role of Reelin in psychiatric diseases is scarce. In order to study the direct influence of Reelin's levels on behavior, we subjected two mouse lines, in which Reelin levels are either reduced (Reelin heterozygous mice) or increased (Reelin overexpressing mice), to a battery of behavioral tests: open-field, black-white box, novelty-suppressed-feeding, forced-swim-test, chronic corticosterone treatment followed by forced-swim-test, cocaine sensitization and pre-pulse inhibition (PPI) deficits induced by N-methyl-D-aspartate (NMDA) antagonists. These tests were designed to model some aspects of psychiatric disorders such as schizophrenia, mood, and anxiety disorders. We found no differences between Reeler heterozygous mice and their wild-type littermates. However, Reelin overexpression in the mouse forebrain reduced the time spent floating in the forced-swim-test in mice subjected to chronic corticosterone treatment, reduced behavioral sensitization to cocaine, and reduced PPI deficits induced by a NMDA antagonist. In addition, we demonstrate that while stress increased NMDA NR2B-mediated synaptic transmission, known to be implicated in depression, Reelin overexpression significantly reduced it. Together, these results point to the Reelin signaling pathway as a relevant drug target for the treatment of a range of psychiatric disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/npp.2011.153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3194085PMC
November 2011

Genome-wide association between branch point properties and alternative splicing.

PLoS Comput Biol 2010 Nov 24;6(11):e1001016. Epub 2010 Nov 24.

Computational Genomics, Universitat Pompeu Fabra, Barcelona, Spain.

The branch point (BP) is one of the three obligatory signals required for pre-mRNA splicing. In mammals, the degeneracy of the motif combined with the lack of a large set of experimentally verified BPs complicates the task of modeling it in silico, and therefore of predicting the location of natural BPs. Consequently, BPs have been disregarded in a considerable fraction of the genome-wide studies on the regulation of splicing in mammals. We present a new computational approach for mammalian BP prediction. Using sequence conservation and positional bias we obtained a set of motifs with good agreement with U2 snRNA binding stability. Using a Support Vector Machine algorithm, we created a model complemented with polypyrimidine tract features, which considerably improves the prediction accuracy over previously published methods. Applying our algorithm to human introns, we show that BP position is highly dependent on the presence of AG dinucleotides in the 3' end of introns, with distance to the 3' splice site and BP strength strongly correlating with alternative splicing. Furthermore, experimental BP mapping for five exons preceded by long AG-dinucleotide exclusion zones revealed that, for a given intron, more than one BP can be chosen throughout the course of splicing. Finally, the comparison between exons of different evolutionary ages and pseudo exons suggests a key role of the BP in the pathway of exon creation in human. Our computational and experimental analyses suggest that BP recognition is more flexible than previously assumed, and it appears highly dependent on the presence of downstream polypyrimidine tracts. The reported association between BP features and the splicing outcome suggests that this, so far disregarded but yet crucial, element buries information that can complement current acceptor site models.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pcbi.1001016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2991248PMC
November 2010

Exon creation and establishment in human genes.

Genome Biol 2008 ;9(9):R141

Computational Genomics, Universitat Pompeu Fabra, Barcelona, Spain.

Background: A large proportion of species-specific exons are alternatively spliced. In primates, Alu elements play a crucial role in the process of exon creation but many new exons have appeared through other mechanisms. Despite many recent studies, it is still unclear which are the splicing regulatory requirements for de novo exonization and how splicing regulation changes throughout an exon's lifespan.

Results: Using comparative genomics, we have defined sets of exons with different evolutionary ages. Younger exons have weaker splice-sites and lower absolute values for the relative abundance of putative splicing regulators between exonic and adjacent intronic regions, indicating a less consolidated splicing regulation. This relative abundance is shown to increase with exon age, leading to higher exon inclusion. We show that this local difference in the density of regulators might be of biological significance, as it outperforms other measures in real exon versus pseudo-exon classification. We apply this new measure to the specific case of the exonization of anti-sense Alu elements and show that they are characterized by a general lack of exonic splicing silencers.

Conclusions: Our results suggest that specific sequence environments are required for exonization and that these can change with time. We propose a model of exon creation and establishment in human genes, in which splicing decisions depend on the relative local abundance of regulatory motifs. Using this model, we provide further explanation as to why Alu elements serve as a major substrate for exon creation in primates. Finally, we discuss the benefits of integrating such information in gene prediction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/gb-2008-9-9-r141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2592719PMC
January 2009