Rodrigues Fernanda Martins, Majeres Leif E, Dilger Anna C, McCann Joshua C, Cassady Christopher J, Shike Dan W, Beever Jonathan E
Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Division of Biological and Biomedical Sciences, Washington University in Saint Louis, Saint Louis, MO, USA.
BMC Genomics. 2025 May 14;26(1):479. doi: 10.1186/s12864-025-11665-z.
The LCORL-NCAPG locus is a major quantitative trait locus (QTL) on bovine chromosome 6 (BTA6) that influences growth and carcass composition in cattle. To further understand the molecular mechanism responsible for the phenotypic changes associated with this locus, twenty-four Charolais-sired calves were selected for muscle transcriptome analysis based on alternative homozygous LCORL-NCAPG haplotypes (i.e., 12 "QQ" and 12 "qq", where "Q" is a haplotype harboring variation associated with increased growth). At 300 days of age, a biopsy of the longissimus dorsi muscle was collected from each animal for RNA sequencing.
Gene expression analysis identified 733 genes as differentially expressed between QQ and qq animals (q-value < 0.05). Notably, LCORL and genes known to be important regulators of growth such as IGF2 were upregulated in QQ individuals, while genes associated with adiposity such as FASN and LEP were downregulated, reflecting the increase in lean growth associated with this locus. Gene set enrichment analysis demonstrated QQ individuals had downregulation of pathways associated with adipogenesis, alongside upregulation of transcripts for cellular machinery essential for protein synthesis and energy metabolism, particularly ribosomal and mitochondrial components.
The differences in the muscle transcriptome between QQ and qq animals imply that muscle hypertrophy may be metabolically favored over accumulation of fat in animals with the QQ haplotype. Our findings also suggest this haplotype could be linked to a difference in LCORL expression that potentially influences the downstream transcriptional effects observed, though further research will be needed to confirm the molecular mechanisms underlying the associated changes in phenotype.
LCORL-NCAPG基因座是牛6号染色体(BTA6)上的一个主要数量性状基因座(QTL),影响牛的生长和胴体组成。为了进一步了解与该基因座相关的表型变化的分子机制,根据纯合子LCORL-NCAPG单倍型的差异(即12个“QQ”和12个“qq”,其中“Q”是携带与生长增加相关变异的单倍型),选择了24头夏洛莱牛后代犊牛进行肌肉转录组分析。在300日龄时,从每只动物身上采集背最长肌活检样本用于RNA测序。
基因表达分析确定了733个基因在QQ和qq动物之间差异表达(q值<0.05)。值得注意的是,LCORL以及已知的重要生长调节因子如IGF2在QQ个体中上调,而与肥胖相关的基因如FASN和LEP下调,这反映了与该基因座相关的瘦肉生长增加。基因集富集分析表明,QQ个体中与脂肪生成相关的途径下调,同时蛋白质合成和能量代谢所必需的细胞机制转录本上调,特别是核糖体和线粒体成分。
QQ和qq动物之间肌肉转录组的差异表明,在具有QQ单倍型的动物中,肌肉肥大在代谢上可能比脂肪积累更受青睐。我们的研究结果还表明,这种单倍型可能与LCORL表达的差异有关,这可能会影响观察到的下游转录效应,不过还需要进一步研究来证实相关表型变化背后的分子机制。