Whole metabolome and genome analyses provide information on the genetic variability affecting the metabolism in pigs

Pig production and reproduction traits are complex phenotypes demanding novel strategies for their genetic improvement. Complexity arises from the interplay within and between different biological layers encompassing the genome, proteome and metabolome spaces. Metabolites are simple and intermediate phenotypes that upon genetic regulation, establish molecular routes resulting in the expression of complexity. As such, the deconstruction of complex phenotypes in their single biological components may be useful to describe the genetic factors affecting economically relevant traits. Here, we obtained the metabolomics profile of about 1300 heavy pigs, including 900 Italian Large White and 400 Italian Duroc pigs. Targeted and untargeted metabolomics was applied to plasma samples to recover abundance levels of about 1000 metabolites. Pigs were also genotyped with the Illumina PorcineSNP60 BeadChip. Metabolomics profiles were initially used to study the metabolite-metabolite relationships and to reconstruct metabolic routes. A Gaussian Graphical Model approach was used for this purpose. Metabolomics profiles were then coupled with genotype data to study the effect of genome variability over the metabolome via genome-wide association studies (GWAS). Association of both single metabolite abundances and metabolites ratios were tested. For each trait, genomic heritability was also estimated. Whole genome sequencing data from hundred animals were then used to identify putative causative mutations. Reconstructed metabolic networks resulted quite similar though differences emerged, pointing out putative breed-specific metabolic routes. Networks were characterized by poorly interconnected modules representing the specific metabolism of the different metabolite classes. Several associations were recovered from GWAS; as expected, the most significant associations were between an enzyme-encoding gene and a metabolite constituting its specific substrate or final product. Overall, we obtained a first catalogue of genes and variants affecting the pig metabolism and that represent a novel source of information for explaining, indirectly, complex traits. This information gives the possibility to include metabolites and novel genetic markers for fine tune breeding and selection programs, to improve sustainability of the pig production sector.