Copy number variation on ABCC2-DNMBP loci affects the diversity and composition of the fecal microbiota in pigs

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• dc.contributor.author Ramayo-Caldas, Yuliaxis
• dc.contributor.author Crespo-Piazuelo, Daniel
• dc.contributor.author Morata, Jordi
• dc.contributor.author González-Rodríguez, Olga
• dc.contributor.author Sebastià, Cristina
• dc.contributor.author Castelló, Anna
• dc.contributor.author Dalmau, Antoni
• dc.contributor.author Ramos-Onsins, Sebastián
• dc.contributor.author Alexiou, Konstantinos G.
• dc.contributor.author Folch, Josep M.
• dc.contributor.author Quintanilla, Raquel
• dc.contributor.author Ballester Devís, Maria
• dc.date.accessioned 2023-09-21T07:01:09Z
• dc.date.available 2023-09-21T07:01:09Z
• dc.date.issued 2023
• dc.description.abstract Genetic variation in the pig genome partially modulates the composition of porcine gut microbial communities. Previous studies have been focused on the association between single nucleotide polymorphisms (SNPs) and the gut microbiota, but little is known about the relationship between structural variants and fecal microbial traits. The main goal of this study was to explore the association between porcine genome copy number variants (CNVs) and the diversity and composition of pig fecal microbiota. For this purpose, we used whole-genome sequencing data to undertake a comprehensive identification of CNVs followed by a genome-wide association analysis between the estimated CNV status and the fecal bacterial diversity in a commercial Duroc pig population. A CNV predicted as gain (DUP) partially harboring ABCC2-DNMBP loci was associated with richness (P = 5.41 × 10-5, false discovery rate [FDR] = 0.022) and Shannon α-diversity (P = 1.42 × 10-4, FDR = 0.057). The in silico predicted gain of copies was validated by real-time quantitative PCR (qPCR), and its segregation, and positive association with the richness and Shannon α-diversity of the porcine fecal bacterial ecosystem was confirmed in an unrelated F1 (Duroc × Iberian) cross. Our results advise the relevance of considering the role of host-genome structural variants as potential modulators of microbial ecosystems and suggest the ABCC2-DNMBP CNV as a host-genetic factor for the modulation of the diversity and composition of the fecal microbiota in pigs. IMPORTANCE A better understanding of the environmental and host factors modulating gut microbiomes is a topic of greatest interest. Recent evidence suggests that genetic variation in the pig genome partially controls the composition of porcine gut microbiota. However, since previous studies have been focused on the association between single nucleotide polymorphisms and the fecal microbiota, little is known about the relationship between other sources of genetic variation, like the structural variants and microbial traits. Here, we identified, experimentally validated, and replicated in an independent population a positive link between the gain of copies of ABCC2-DNMBP loci and the diversity and composition of pig fecal microbiota. Our results advise the relevance of considering the role of host-genome structural variants as putative modulators of microbial ecosystems and open the possibility of implementing novel holobiont-based management strategies in breeding programs for the simultaneous improvement of microbial traits and host performance.
• dc.description.sponsorship The project was funded by the Spanish Ministry of Science and Innovation-State Research Agency (Agencia Española de Investigación (AEI), Spain, 10.13039/501100011033) grants PID2020-112677RB-C21 (M.B.) and PID2021-126555OB-I00 (Y.R.-C.) and the GENE-SWitCH project (https://www.gene-switch.eu) funded by the European Union’s Horizon 2020 research and innovation program under grant agreement 817998 (M.B. and D.C.-P.). S.R.-O. is supported by grant PID2020-119255GB-I00 (Ministerio de Ciencia e Innovación de España (MICINN), Spain) and by the CERCA Program/Generalitat de Catalunya. The Centre for Research in Agricultural Genomics acknowledges financial support from the Spanish Ministry of Economy and Competitiveness through grants SEV-2015-0533 and CEX2019-000917 from the Severo Ochoa Program for Centers of Excellence in R&D 2016 to 2019 and 2020 to 2023 and the European Regional Development Fund. Y.R.-C. is recipient of Ramon y Cajal postdoctoral fellowship RYC2019-027244-I funded by the Spanish Ministry of Science and Innovation. C.S. is funded by AGUAR grant 2020FI_B 00225. D.C.-P., M.B, O.G.-R., R.Q., and Y.R.-C. belonged to a Consolidated Research Group Agencia de Gestión de Ayudas Universitarias y de Investigación de Catalunya (AGAUR), reference 2017SGR-1719.
• dc.format.mimetype application/pdf
• dc.identifier.citation Ramayo-Caldas Y, Crespo-Piazuelo D, Morata J, González-Rodríguez O, Sebastià C, Castello A, Dalmau A, Ramos-Onsins S, Alexiou KG, Folch JM, Quintanilla R, Ballester M. Copy number variation on ABCC2-DNMBP loci affects the diversity and composition of the fecal microbiota in pigs. Microbiol Spectr. 2023 Aug 17;11(4):e0527122. DOI: 10.1128/spectrum.05271-22
• dc.identifier.doi http://dx.doi.org/10.1128/spectrum.05271-22
• dc.identifier.issn 2165-0497
• dc.identifier.uri http://hdl.handle.net/10230/57930
• dc.language.iso eng
• dc.publisher American Society for Microbiology
• dc.relation.ispartof Microbiol Spectr. 2023 Aug 17;11(4):e0527122
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/817998
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2020-112677RB-C21
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2020-119255GB-I00
• dc.rights © 2023 Ramayo-Caldas et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Diversity
• dc.subject.keyword Microbiota
• dc.subject.keyword Modulators
• dc.subject.keyword Porcine
• dc.subject.keyword Structural variants
• dc.title Copy number variation on ABCC2-DNMBP loci affects the diversity and composition of the fecal microbiota in pigs
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion