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

Background 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 gut microbial traits. Results The main goal of this study was to assess the effect of porcine genome copy number variants (CNVs) on the diversity and composition of pig gut 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 gut bacterial diversity in a commercial Duroc pig population. A CNV predicted as gain (DUP) partially harboring ABCC2-DNMBP loci was associated with richness ( p -value=5.41×10−5) and Shannon α-diversity ( p -value=1.42×10−4). 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 gut bacterial ecosystem was confirmed in an unrelated F1 (Duroc×Iberian) cross. Furthermore, despite genetic and environmental differences between both populations, the gut microbiota of DUP samples showed a significant over-abundance of the Desulfovibrio, Blautia, Phascolarctobacterium, Faecalibacterium, Succinivibrio and Anaerovibrio genera. Conclusions In summary, this is the first study that evaluate the putative modulatory role of CNVs on pig gut microbiota. Our results advice the relevance of considering the role of host-genome structural variants as 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 gut microbiota in pigs. ### Competing Interest Statement The authors have declared no competing interest. * QIIME2 : Quantitative insights into microbial ecology GWAS : Genome-wide association studies SNP : Single nucleotide polymorphisms CNV : Copy number variants CNVR : Copy number variant region DUP : CNV predicted as gain BA : Bile acids ATajima : Tajima’s theta estimator or nucleotide diversity RTajima : Relative Tajima’s theta estimator