Genomic analysis of energy metabolism and its impact on production traits in pigs

Abstract

Pork is one of the most consumed meats around the world and plays a dominant role in the meat market. Therefore, the demand for pork leads to the rapid development of intensive farming. However, the rise of intensive farming increases the risk of animal pathogens spreading, which in turn leads to the persistent use of antibiotics and results in significant antibiotic resistance. Meanwhile, the European Commission demands to reduce the antibiotic utilization. The goal of current breeding is not only to improve production performance and product quality but also to integrate health-related traits to address these challenges. We investigated the molecular mechanisms determining the fatty acid (FA) profile and metabolism in different pig tissues. In detail, we identified a total of 30 regions on 15 chromosomes of the porcine genome that were associated with FA composition traits across blood, liver, adipose tissue, and muscle. Forty-nine candidate genes were annotated in these genomic regions and are related to lipid metabolism, energy production, and membrane structure maintenance, as well as participate in signaling pathways and regulate inflammation by promoting lipogenesis. These findings can be useful in selection programs aiming at improving health without compromising productivity. Moreover, a data integration approach was used to explore the FA crosstalk among tissues and to identify potential early blood biomarkers for predicting carcass traits and muscle FA profiles. Plasma C16:0 and C16:1n-7 and their ratios, together with C18:1n-9 and C18:2n-6 in Duroc pigs at early growth stage, were proposed for predicting FA composition in liver, backfat, and muscle after pig slaughter. Furthermore, these blood FAs are positively correlated with carcass weight and fat thickness, while negatively correlated with lean meat percentage. Finally, we validated by cell transfection and luciferase assays the effect of the ELOVL6:c.-394G>A polymorphism on the ELOVL6 gene expression. The results obtained support the hypothesis that the binding of transcription factor ERα at ELOVL6 promoter induces its methylation and results in a decrease of ELOVL6 gene expression in animals with ELOVL6:c.-394G allele. Furthermore, our study demonstrated through site-directed mutagenesis of the ELOVL6:c.-480C>T polymorphism, located within an SP1 transcription factor binding site, that the protective role of SP1 against DNA methylation is not the primary factor contributing to the differential expression of the ELOVL6 gene. In addition, we identified the polymorphism rs339777757 in the APOA2 promoter and showed that this SNP was the most significantly associated with liver APOA2 expression in an eGWAS analysis. Additionally, the in-silico transcription factor prediction identified that the rs339777757 is located at the binding site of RORα, a widely reported transcription factor for human APOA1 and APOA5 genes. A luciferase assay was conducted with two constructs, one carrying the C allele and the other the T allele, to validate the regulatory effect of rs339777757. We observed that the construct with the C allele exhibited a suggestive higher APOA2 gene expression in comparison with the T allele construct, which may be attributed to the RORα binding.

Date of Award	4 Nov 2024
Original language	English
Supervisor	Maria Ballester Devis (Director) & Josep Maria Folch Albareda (Director)