Defining the genetic and evolutionary architecture of alternative splicing in response to infection
| Autor: | Lluis Quintana-Murci, Hélène Quach, Maxime Rotival |
|---|---|
| Přispěvatelé: | Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), This project was funded by the European Research Council under the European Union’s Seventh Framework Programme (FP/2007–2013)/ERC grant agreement 281297 (to L.Q.-M.). The Quintana-Murci lab is funded by the French Government’s Investissement d’Avenir program, Laboratoires d’Excellence 'Integrative Biology of Emerging Infectious Diseases' (ANR-10-LABX-62-IBEID) and the Fondation pour la Recherche Médicale (Equipe FRM DEQ20180339214). M.R. was supported by a Marie Skłodowska-Curie fellowship (DLV-655417)., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 281297,EC:FP7:ERC,ERC-2011-StG_20101109,EVOIMMUNOPOP(2012), European Project: 655417,H2020,H2020-MSCA-IF-2014,GATTACA(2015), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male MESH: Selection Genetic General Physics and Astronomy 02 engineering and technology MESH: Protein Isoforms MESH: Sequence Analysis RNA Protein Isoforms MESH: Animals MESH: Genetic Variation MESH: Healthy Volunteers lcsh:Science MESH: Immunity Neanderthals MESH: Neanderthals education.field_of_study Multidisciplinary Repertoire MESH: Alternative Splicing MESH: Polymorphism Single Nucleotide [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE] MESH: Infections MESH: European Continental Ancestry Group 021001 nanoscience & nanotechnology Biological Evolution Healthy Volunteers RNA splicing 0210 nano-technology Gene isoform Science Population Quantitative Trait Loci Introgression Black People MESH: Biological Evolution Biology Infections Polymorphism Single Nucleotide General Biochemistry Genetics and Molecular Biology White People Article 03 medical and health sciences Immune system MESH: Whole Exome Sequencing Exome Sequencing Animals Humans Selection Genetic education Local adaptation MESH: Humans [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE] Sequence Analysis RNA MESH: Transcriptome Alternative splicing Immunity Genetic Variation General Chemistry MESH: Male MESH: Quantitative Trait Loci Alternative Splicing 030104 developmental biology [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics Evolutionary biology lcsh:Q MESH: African Continental Ancestry Group Transcriptome |
| Zdroj: | Nature Communications Nature Communications, Nature Publishing Group, 2019, 10 (1), pp.1671. ⟨10.1038/s41467-019-09689-7⟩ Nature Communications, 2019, 10 (1), pp.1671. ⟨10.1038/s41467-019-09689-7⟩ Nature Communications, Vol 10, Iss 1, Pp 1-15 (2019) |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-019-09689-7⟩ |
| Popis: | Host and environmental factors contribute to variation in human immune responses, yet the genetic and evolutionary drivers of alternative splicing in response to infection remain largely uncharacterised. Leveraging 970 RNA-sequencing profiles of resting and stimulated monocytes from 200 individuals of African- and European-descent, we show that immune activation elicits a marked remodelling of the isoform repertoire, while increasing the levels of erroneous splicing. We identify 1,464 loci associated with variation in isoform usage (sQTLs), 9% of them being stimulation-specific, which are enriched in disease-related loci. Furthermore, we detect a longstanding increased plasticity of immune gene splicing, and show that positive selection and Neanderthal introgression have both contributed to diversify the splicing landscape of human populations. Together, these findings suggest that differential isoform usage has been an important substrate of innovation in the long-term evolution of immune responses and a more recent vehicle of population local adaptation. Genetic ancestry might influence immunological response to infection at different regulatory levels. Here, the authors use RNA-Seq to investigate the variability of alternative splicing patterns in resting and stimulated monocytes of African- and European-descent. |
| Databáze: | OpenAIRE |
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