Molecular characterization of the ACSS2 gene involved in adaptation to hypoxia in high-altitude cattle breeds
Molecular characterization of the ACSS2 gene involved in adaptation to hypoxia in high-altitude cattle breeds
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参与高海拔牛品种缺氧适应的 ACSS2 基因的分子特征
DOI：
10.1163/15707563-bja10046
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发表时间：
2020-10
期刊：
影响因子：
1.2
通讯作者：
Huang Jinming
中科院分区：
文献类型：
--
作者：
Zhao Han;Gao Yaping;Jiang Qiang;Wang Jinpeng;Liu Wenhao;Ju Zhihua;Wang Xiuge;Wei Xiaochao;Gao Yundong;Huang Jinming
在低氧、营养不足、葡萄糖缺乏等极端环境条件下，乙酰辅酶A合成酶2(ACSS2)介导的乙酰辅酶A合成途径在保证代谢活动的正常运行中起着替代作用。为了探讨ACSS2基因在高原黄牛品种低氧适应中的潜在作用及其基因表达调控机制，本研究对分布在不同海拔(95-3850m)的5个黄牛品种、黄牛品种、杂交黄牛品种以及分布在不同海拔(95-3850m)的两个牦牛品种进行了ACSS2基因的遗传变异分析。在7个群体中共检测到58个SNPs，并在高海拔品种中发现了丰富的遗传变异。通过荧光素酶活性测定，我们在FFB和HepG2细胞中鉴定出牛ACSS2核心启动子区域位于g.-682和g.-264之间。我们还鉴定了高原低氧特异性单倍型(CAGTCT)由6个高度连锁的SNP组成。TagSNP g.-473T>；C(Rs23)位于牛、金牛、金牛和牦牛中ACSS2的核心启动子。构建了含有rs23基因的重组载体，并对不同基因类型的荧光素酶活性进行了分析，结果表明，T突变为C后，ACSS2启动子的活性显著提高。在牦牛品种的启动子中还发现了一个含有12个碱基(g.-562 ins GAAAGGACCCTA)的SNP Rs20。荧光素酶活性分析表明，插入突变体显著降低了ACSS2的启动子活性。因此，ACSS2可能通过产生适应性等位基因来影响牛的基因转录，从而在适应高海拔低氧的过程中发挥重要作用。这些结果表明，不同的遗传变异和单倍型影响核心启动子调节ACSS2基因表达的活性，从而克服和适应不同品种牛的高海拔环境。我们的研究结果可能对理解牛的高原适应机制和分子育种的应用具有重要意义。
Under extreme environmental conditions such as hypoxia, insufficient nutrition, and glucose deficiency, the acetyl-CoA synthetase 2 (ACSS2)-mediated acetyl-CoA synthesis pathway plays an alternative role to ensure the normal operation of metabolic activities. To investigate the potential effect of the ACSS2 gene on hypoxic adaptation and its regulatory mechanism of gene expression in high-altitude cattle breeds, we analyzed the genetic variations of the ACSS2 gene in five Bos taurus taurus, Bos taurus indicus, hybrid Bos taurus taurus × Bos taurus indicus Chinese cattle breeds, and two Bos grunniens (yak) breeds distributed at different altitudes (95-3850 m). A total of 58 SNPs was detected in seven populations, and abundant genetic variation was found in high-altitude breeds. We identified the bovine ACSS2 core promoter region between g.-682 and g.-264 by using the luciferase assay in FFB and HepG2 cells. We also identified that the high-altitude hypoxia-specific haplotype (CAGTCT) was composed of six highly linked SNPs. The tagSNP g.-473 T>C (rs23) is located in the core promoter of ACSS2 in the Bos taurus taurus and yak breeds. The recombinant plasmid containing rs23 and analyses of luciferase activity of different genotypes showed that the activity of ACSS2 promoter increased significantly when T was mutated to C. We also found a yak-specific SNP rs20 that consists of 12 base insertions (g.-562 ins GAAAGGACCCTA) in the promoter of yak breeds. Luciferase activity analysis showed that the insertion mutant significantly decreased the promoter activity of ACSS2. Hence, ACSS2 may play an important role in the adaptation to high-altitude hypoxia by generating adaptive alleles to influence gene transcription in cattle. These results signify that different genetic variants and haplotypes affect the activity of the core promoter to regulate ACSS2 gene expression and subsequently overcome and adapt to a high-altitude environment within different cattle breeds. Our findings may have important implications for understanding the mechanism of adaptation to high altitude and for application of molecular breeding in Bos species.