解析猪肉中嘌呤含量的遗传学基础

doi:10.1016/j.jia.2024.05.004

摘要/Abstract

摘要： 作为食物中一种重要的营养指标，嘌呤碱基含量的重要性源于它拥有通过高嘌呤饮食引起人体高尿酸血症或痛风的潜在能力。包括猪肉在内的畜肉中普遍含有中等偏高的总嘌呤含量。近期的研究表明不同猪种内或猪种间在嘌呤含量上存在着巨大差异，意味着遗传因素对该性状上的影响。因此，本研究旨在解析调控猪肉中嘌呤碱基含量的遗传基础。结果显示，四种嘌呤性状（鸟嘌呤、腺嘌呤、次黄嘌呤、总嘌呤）的遗传力估计值从0.14到0.35不等，且四种嘌呤碱基总共识别到的数量性状位点（QTL）总数分别为14、36、19、25。关于总嘌呤的基因集富集分析和基因网络分析结果显示，一个由15个强候选基因互相交织形成的复杂网络涉及了众多的嘌呤代谢通路，如嘌呤核糖核苷酸代谢过程、嘌呤核苷酸代谢和转运、嘌呤回收途径等。特别的，我们发现大多数与总嘌呤含量显著相关的遗传变异位点对多个嘌呤碱基表现出类似的影响。我们还在猪的12号染色体上识别到两个极显著（P < 10^-12）的QTL，其中一个影响鸟嘌呤含量，另一个同时影响腺嘌呤和次黄嘌呤含量水平。我们发现位于12号染色体上与鸟嘌呤相关的最显著位点处在TMEM238L基因下游1.1kb处并且在H3K27me3组蛋白修饰包含的基因组片段内，而通过精细定位策略将位于同一染色体上与腺嘌呤及次黄嘌呤均相关的QTL位点缩小至了172kb的区域，此区域内包含了GAS7和MYH13两个基因。然而，此QTL的效应并不能被这两个基因中的任一错义突变解释。本研究首次揭示了与家畜嘌呤含量相关的遗传变异位点及候选基因，为低嘌呤含量猪品系的选择性育种奠定了坚实的基础。

Abstract:

The significance of purine base content as an important nutrition indicator in foods arises from its potential to trigger hyperuricemia or gout via high-purine diet. Livestock meats, including pork, generally contain moderate to high total purine content (TP). Recent research revealed substantial variations within and across pig breeds, implying genetic factors influencing this trait. Thus, this study aimed to unravel the genetic underpinnings governing purine base content in pork. The heritability estimates (h²) for the four purine traits ranged from 0.14 to 0.35. A total of 14, 36, 19 and 25 quantitative trait loci (QTLs) were identified for guanine, adenine, hypoxanthine, and TP, respectively. Our comprehensive gene set enrichment analysis and gene network analysis revealed 15 promising candidate genes intricately interwoven within diverse purine metabolism pathways, such as purine ribonucleotide metabolic process, purine nucleotide metabolism and transport, and purine salvage pathways, all contributing to TP. Strikingly, most genetic variants significantly associated with TP displayed analogous effects on multiple purine bases. Two distinct and highly significant QTLs (P<10^–12) emerged on Sus scrofa chromosome (SSC) 12: one impacting guanine content and the other concurrently influencing adenine and hypoxanthine levels. The peak of the guanine QTL on SSC12 resided 1.1 kb downstream of the transmembrane protein 238 like (TMEM238L) gene and is encapsulated within a genomic segment characterized by the histone modification H3K27me3. Focused fine-mapping for the SSC12 QTL associated with adenine and hypoxanthine levels narrowed its scope to around 172 kb, encompassing the growth arrest specific 7 (GAS7) and myosin heavy chain 13 (MYH13) genes. However, the observed QTL effect was not attributed to any missense mutations within the two genes. This pioneering study unveils the genetic variations and candidate genes associated with purine content in livestock, laying a robust foundation for the selective breeding of pig lines with reduced purine base content.

Key words: pig , purine content , genetic architecture , GWAS , QTL

Cong Huang, Min Zheng, Yizhong Huang, Liping Cai, Xiaoxiao Zou, Tianxiong Yao, Xinke Xie, Bin Yang, Shijun Xiao, Junwu Ma, Lusheng Huang. 解析猪肉中嘌呤含量的遗传学基础[J]. Journal of Integrative Agriculture, 2026, 25(3): 1099-1113.

Cong Huang, Min Zheng, Yizhong Huang, Liping Cai, Xiaoxiao Zou, Tianxiong Yao, Xinke Xie, Bin Yang, Shijun Xiao, Junwu Ma, Lusheng Huang. Unraveling genetic underpinnings of purine content in pork[J]. Journal of Integrative Agriculture, 2026, 25(3): 1099-1113.

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