Abstract
Systems biology approaches are used as strategy to uncover tissue-specific perturbations and regulatory genes related to complex phenotypes. We applied this approach to study feed efficiency (FE) in beef cattle, an important trait both economically and environmentally. Poly-A selected RNA of five tissues (adrenal gland, hypothalamus, liver, skeletal muscle and pituitary) of eighteen young bulls, selected for high and low FE, were sequenced (Illumina HiSeq 2500, 100 bp, pared-end). From the 17,354 expressed genes considering all tissues, 1,335 were prioritized by five selection categories (differentially expressed, harboring SNPs associated with FE, tissue-specific, secreted in plasma and key regulators) and used for network construction. NR2F6 and TGFB1 were identified and validated by motif discovery as key regulators of hepatic inflammatory response and muscle tissue development, respectively, two biological processes demonstrated to be associated with FE. Moreover, we indicated potential biomarkers of FE, which are related to hormonal control of metabolism and sexual maturity. By using robust methodologies and validation strategies, we confirmed the main biological processes related to FE in Bos indicus and indicated candidate genes as regulators or biomarkers of superior animals.
Highlights
Since the domestication of the first species, animal selection aims to meet human needs and their changes over time
Differential expression (DE) analysis between high feed efficiency (HFE) and low feed efficiency (LFE) animals resulted in 471 differentially expressed (DE) genes across tissues (P < 0.001, Supplementary Image 1), namely, 111 in adrenal gland, 125 in hypothalamus, 91 in liver, 104 in muscle and 98 in pituitary (Supplementary Tables 2A–E)
No significant functional enrichment was found for the 281 genes up-regulated in HFE group, the 248 genes down-regulated presented a significant enrichment of GO terms such as response to hormone (Padj = 5.43 × 10−6), regulation of hormone levels (Padj = 3.48 × 10−6), cell communication (Padj = 3.18 × 10−4), regulation of signaling receptor activity (Padj = 3.20 × 10−4), hormone metabolic process (Padj = 5.86 × 10−4), response to corticosteroid (Padj = 6.28 × 10−4), regulation of secretion (Padj = 7.2 × 10−4), response to lipopolysaccharide (Padj = 7.9 × 10−4) and regulation of cell proliferation (Padj = 1.86 × 10−3)
Summary
Since the domestication of the first species, animal selection aims to meet human needs and their changes over time. Feed efficiency (FE) has become a relevant trait of study, as animals considered of high feed efficiency are those presenting reduced feed intake and lower production of methane and manure without compromising animal’s weight gain (Gerber et al, 2013). Feed intake and weight gain for a large number of animals need to be recorded for at least 70 days to obtain accurate estimates of FE (Archer et al, 1997). Several studies have been carried out with the aim to identify molecular markers associated with FE to enable a faster and cost-effective identification of superior animals
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