Animal Breeding and Genetics Program, Institute of Agrifood Research and Technology, Caldes de Montbui, Spain.
Centro Nacional de Análisis Genómico, Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain.
Microbiol Spectr. 2023 Aug 17;11(4):e0527122. doi: 10.1128/spectrum.05271-22. Epub 2023 May 31.
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 ( = 5.41 × 10, false discovery rate [FDR] = 0.022) and Shannon α-diversity ( = 1.42 × 10, FDR = 0.057). The 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. 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 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.
猪基因组中的遗传变异部分调节了猪肠道微生物群落的组成。先前的研究集中于单核苷酸多态性（SNP）与肠道微生物群之间的关联，但对结构变异与粪便微生物特征之间的关系知之甚少。本研究的主要目的是探索猪基因组拷贝数变异（CNV）与猪粪便微生物多样性和组成之间的关联。为此，我们使用全基因组测序数据进行了全面的 CNV 鉴定，然后在商业杜洛克猪群体中进行了基于估计的 CNV 状态与粪便细菌多样性之间的全基因组关联分析。一个预测为增益（DUP）的 CNV 部分含有 ABCC2-DNMBP 基因座，与丰富度（=5.41×10，错误发现率 [FDR]=0.022）和 Shannon α-多样性（=1.42×10，FDR=0.057）相关。通过实时定量 PCR（qPCR）验证了预测的增益拷贝数，在无关的 F1（杜洛克×伊比利亚）杂交中证实了其分离和与猪粪便细菌生态系统丰富度和 Shannon α-多样性的正相关。我们的结果表明，宿主基因组结构变异作为微生物生态系统潜在调节剂的作用是值得考虑的，并提示 ABCC2-DNMBP CNV 是调节猪粪便微生物多样性和组成的宿主遗传因素。更好地了解调节肠道微生物组的环境和宿主因素是最感兴趣的主题。最近的证据表明，猪基因组中的遗传变异部分控制了猪肠道微生物群的组成。然而，由于先前的研究集中于 SNP 与粪便微生物群之间的关联，因此对于其他遗传变异来源（如结构变异和微生物特征）之间的关系知之甚少。在这里，我们鉴定、实验验证并在一个独立的群体中复制了 基因座拷贝数增益与猪粪便微生物多样性和组成之间的正相关关系。我们的结果表明，考虑宿主基因组结构变异作为微生物生态系统潜在调节剂的作用是有意义的，并为在繁殖计划中实施新的基于整体生物的管理策略以同时改善微生物特征和宿主性能开辟了可能性。
