Impact and Evolutionary Determinants of Neanderthal Introgression on Transcriptional and Post-Transcriptional Regulation
| Autor: | Lluis Quintana-Murci, Martin Silvert, Maxime Rotival |
|---|---|
| Přispěvatelé: | Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), ED 515 - Complexité du vivant, Sorbonne Université (SU), This work was supported by the Institut Pasteur, the Centre National de la Recherche Scientifique (CNRS), and the Agence Nationale de la Recherche (ANR) grants: 'IEIHSEER' ANR-14-CE14-0008-02 and 'TBPATHGEN' ANR-14-CE14-0007-02. The laboratory of L.Q.M. has received funding from the French government’s Investissement d’Avenir program, Laboratoire d’Excellence 'Integrative Biology of Emerging Infectious Diseases' (grant no. ANR-10- LABX-62-IBEID). M.S. was funded by the Ecole Doctorale 'Complexité du vivant,' Sorbonne Université (contract n°2532/2016)., ANR-14-CE14-0008,IEIHSEER,L'encéphalite Herpétique de l'enfant résulte de déficits héréditaires d'immunité contre l'HSV-1: une exception ou une règle?(2014), ANR-14-CE14-0007,TBPATHGEN,Dissection de la pathogenèse de la tuberculose par l'identification de défauts monogéniques de l'immunité dans les formes pédiatriques sévères de la maladie(2014), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Neanderthal
Transcription Genetic MESH: Selection Genetic T-Lymphocytes promoters adaptation Genome 0302 clinical medicine MESH: Gene Expression Regulation Developmental MESH: Animals RNA Processing Post-Transcriptional Genetics (clinical) MESH: Evolution Molecular Neanderthals MESH: Neanderthals Regulation of gene expression Recombination Genetic 0303 health sciences Adipogenesis MESH: Genomics MESH: Polymorphism Single Nucleotide [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE] Gene Expression Regulation Developmental Genomics Adaptation Physiological Adipose Tissue Regulatory sequence miRNAs MESH: Recombination Genetic MESH: Adipose Tissue MESH: RNA Processing Post-Transcriptional Introgression Biology Polymorphism Single Nucleotide Evolution Molecular 03 medical and health sciences biology.animal Report Genetics Animals Humans Selection Genetic Enhancer Post-transcriptional regulation MESH: Genome Human 030304 developmental biology MESH: Humans [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE] Genome Human T-cells MESH: Transcription Genetic immunity MESH: Adaptation Physiological MicroRNAs MESH: T-Lymphocytes Evolutionary biology enhancers archaic introgression Adaptation gene regulation MESH: Adipogenesis MESH: MicroRNAs 030217 neurology & neurosurgery |
| Zdroj: | American Journal of Human Genetics American Journal of Human Genetics, Elsevier (Cell Press), 2019, 104 (6), pp.1241-1250. ⟨10.1016/j.ajhg.2019.04.016⟩ American Journal of Human Genetics, 2019, 104 (6), pp.1241-1250. ⟨10.1016/j.ajhg.2019.04.016⟩ |
| ISSN: | 0002-9297 1537-6605 |
| DOI: | 10.1016/j.ajhg.2019.04.016⟩ |
| Popis: | Archaic admixture is increasingly recognized as an important source of diversity in modern humans, with Neanderthal haplotypes covering 1-3% of the genome of present-day Eurasians. Recent work has shown that archaic introgression has contributed to human phenotypic diversity, mostly through the regulation of gene expression. Yet, the mechanisms through which archaic variants alter gene expression, and the forces driving the introgression landscape at regulatory regions remain elusive. Here, we explored the impact of archaic introgression on transcriptional and post-transcriptional regulation, focusing on promoters and enhancers across 127 different tissues as well as microRNA-mediated regulation. Although miRNAs themselves harbor few archaic variants, we found that some of these variants may have a strong impact on miRNA-mediated gene regulation. Enhancers were by far the regulatory elements most affected by archaic introgression, with one third of the tissues tested presenting significant enrichments. Specifically, we found strong enrichments of archaic variants in adipose-related tissues and primary T cells, even after accounting for various genomic and evolutionary confounders such as recombination rate and background selection. Interestingly, we identified signatures of adaptive introgression at enhancers of some key regulators of adipogenesis, raising the interesting hypothesis of a possible adaptation of early Eurasians to colder climates. Collectively, this study sheds new light onto the mechanisms through which archaic admixture have impacted gene regulation in Eurasians and, more generally, increases our understanding of the contribution of Neanderthals to the regulation of acquired immunity and adipose homeostasis in modern humans. |
| Databáze: | OpenAIRE |
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