猪DGAT2基因3’-UTR区的多态性鉴定及功能初步分析
摘要
DGAT2(乙酰辅酶A:二酰基甘油酰基转移酶,diacylglycerolacyl transferase,DGAT)是属于酰基辅酶A单酰甘油酰基转移酶(MGAT)家族中的一员,催化能量分子甘油三酯合成的最后一步反应并对其限速,这步反应使二酰甘油(diacylgycerol,DAG)加上脂肪酸酰基辅酶A以共价键结合形成三酰甘油(TG)。DGAT2的表达调控可能控制着动物体内脂肪合成进而影响肉质等生产性状。
本研究采用克隆测序的方法寻找DGAT2基因3′-UTR区的多态性,在包括279头约克夏、96头长白、190头杜洛克、95头鲁莱黑猪、37头莱芜猪、57头大蒲莲和141头军牧一号在内的猪群中检测PS905位点13bp插入/缺失的多态性分布,对有生产性能记录的141头军牧一号猪群体进行基因型与性状数据的关联分析,最后通过生物信息学分析和在细胞水平检测构建的不同基因型3′-UTR载体pGL3-LUC-A和pGL3- LUC-B对报告基因表达的影响,分析PS905位点13bp插入缺失多态的生物学功能。研究结果如下:(1)DGAT2基因3′-UTR区终止密码子之后905bp(PS905)处有一个13bp(TCCTCTGACCTGC)的插入/缺失多态。(2)在所检测的约克夏、长白、杜洛克、鲁莱黑、莱芜猪、大蒲莲、军牧一号群体中AA型均为优势基因型,χ2检测显示所有的猪种该位点均处于哈代温伯格平衡状态。A等位基因频率变化趋势为:地方猪种>育成品种>西方品种。(3)在军牧一号猪群体中,AA基因型的校正背膘厚大于AB基因型,差异极显著(P<0.01);瘦肉率小于AB型,差异显著(P<0.05)。(4)不同类型3′-UTR荧光素酶载体的转染结果表明:pGL3-LUC-B型荧光素酶活性与pGL3-LUC-A但是差异不显著(P=0.0672),B型略高。(5)3′-UTR的RNA二级结构预测结果表明A型的最小自由能更小,更加趋于稳定。
综上所述,DGAT2基因3′-UTR区PS905位点13bp插入型为优势基因型,数据关联分析表明此位点与背膘厚和瘦肉率数据显著相关,AA基因型趋于使背膘增厚,瘦肉率下降。瞬时转染实验显示的结果显示pGL3-LUC-A型载体表达较低,这与数据关联分析结果一致。该位点对于脂肪沉积的影响有待进一步研究。
DGAT2 (acyl-CoA: diacylglycerol acyltransferase) is a member of acyl-CoA: monoacylglycerol acyltransferase (MGAT) family. In the final reaction of triacylglycerols (TG) synthesis pathways, a fatty acyl-CoA and diacylglycerol (DG) molecule is covalently joined to form TG, which is catalyzed and rate-limited by acyl-CoA: diacylglycerol acyltransferase enzymes. The expression and regulation of DGAT2 may control TG synthesis pathway and affect meat traits. The 3′untranslated region (3′-UTR) of porcine DGAT2 gene was screened for polymorphic site using the method of cloning and sequencing, and a 13bp INS/DEL polymorphism in 905bp post stop codon TGA (PS 905) was identified,alleles A and B representing insertion and deletion of 13 bp, respectively. Polymorphism at site PS 905 was analysed by 15% PAGE in Yorkshire, Landrace, Duroc, Lulai Black pigs, Dapulian, Laiwu and Junmu No. 17 different pig breeds. Associations of polymorphism with trait data were analyzed in 141 Junmu No. 1 individuals. Two vectors carried different 3′-UTR with 13bp insertion or deletion at site PS905, named pGL3-LUC-A and pGL3-LUC-B respectively, was constructed. Their effect on gene expression was analyzed in vitro by transient transfection of the individual reporter constructs into 3T3-l1 cells. The results are summarized as follows: 1) There is a polymorphic site in DGAT2 3′-UTR with 13bp fragment (TCCTCTGACCTGC) insertion or deletion; 2). Genotyping of PS905 polymorphic locus in Yorkshire, Landrace, Duroc, Lulai Black, Dapulian, Laiwu and Junmu No. 1 pigs shows that INS/INS is dominant in all these breeds;χ2 test indicates that all the populations tested were in a state of Hardy-Weinberg equilibrium and the frequency of allele A was higher in Chinese local pig breeds than in cultivated pig breeds and was the lowest in western breeds. 3). Association analysis on Junmu No. 1 data indicates that backfat thickness of individuals with genotype AA is significantly higher than AB individuals (P<0.01), and lean percentage of individuals with genotype AA is significantly higher than AB individuals (P<0.05). 4) In vitro study indicated that there is no significant difference in the activities of driving reporter gene transcription between pGL3-LUC-A and pGL3-LUC-B constructs (P =0.0672). 5) RNA structures predicted by Mfold show that secondary structure of 3′-UTR with 13bp insertion is more stable than deletion type.
Collectively, the present study shows that 13bp insertion is dominant on PS905 locus of DGAT2 3′-UTR in pigs. Association analysis indicates that allele A has higher backfat thickness and lower lean percentage. The transfection experiment with different 3′-UTR of reporter gene showed no significant differerces. The result that the activity of driving reporter gene transcription of pGL3-LUC-B is slightly higher is consistent with association analysis. Further studies need to be carried out to elucidate the effect of DGAT2 on fat deposition and pork quality.
本研究采用克隆测序的方法寻找DGAT2基因3′-UTR区的多态性,在包括279头约克夏、96头长白、190头杜洛克、95头鲁莱黑猪、37头莱芜猪、57头大蒲莲和141头军牧一号在内的猪群中检测PS905位点13bp插入/缺失的多态性分布,对有生产性能记录的141头军牧一号猪群体进行基因型与性状数据的关联分析,最后通过生物信息学分析和在细胞水平检测构建的不同基因型3′-UTR载体pGL3-LUC-A和pGL3- LUC-B对报告基因表达的影响,分析PS905位点13bp插入缺失多态的生物学功能。研究结果如下:(1)DGAT2基因3′-UTR区终止密码子之后905bp(PS905)处有一个13bp(TCCTCTGACCTGC)的插入/缺失多态。(2)在所检测的约克夏、长白、杜洛克、鲁莱黑、莱芜猪、大蒲莲、军牧一号群体中AA型均为优势基因型,χ2检测显示所有的猪种该位点均处于哈代温伯格平衡状态。A等位基因频率变化趋势为:地方猪种>育成品种>西方品种。(3)在军牧一号猪群体中,AA基因型的校正背膘厚大于AB基因型,差异极显著(P<0.01);瘦肉率小于AB型,差异显著(P<0.05)。(4)不同类型3′-UTR荧光素酶载体的转染结果表明:pGL3-LUC-B型荧光素酶活性与pGL3-LUC-A但是差异不显著(P=0.0672),B型略高。(5)3′-UTR的RNA二级结构预测结果表明A型的最小自由能更小,更加趋于稳定。
综上所述,DGAT2基因3′-UTR区PS905位点13bp插入型为优势基因型,数据关联分析表明此位点与背膘厚和瘦肉率数据显著相关,AA基因型趋于使背膘增厚,瘦肉率下降。瞬时转染实验显示的结果显示pGL3-LUC-A型载体表达较低,这与数据关联分析结果一致。该位点对于脂肪沉积的影响有待进一步研究。
DGAT2 (acyl-CoA: diacylglycerol acyltransferase) is a member of acyl-CoA: monoacylglycerol acyltransferase (MGAT) family. In the final reaction of triacylglycerols (TG) synthesis pathways, a fatty acyl-CoA and diacylglycerol (DG) molecule is covalently joined to form TG, which is catalyzed and rate-limited by acyl-CoA: diacylglycerol acyltransferase enzymes. The expression and regulation of DGAT2 may control TG synthesis pathway and affect meat traits. The 3′untranslated region (3′-UTR) of porcine DGAT2 gene was screened for polymorphic site using the method of cloning and sequencing, and a 13bp INS/DEL polymorphism in 905bp post stop codon TGA (PS 905) was identified,alleles A and B representing insertion and deletion of 13 bp, respectively. Polymorphism at site PS 905 was analysed by 15% PAGE in Yorkshire, Landrace, Duroc, Lulai Black pigs, Dapulian, Laiwu and Junmu No. 17 different pig breeds. Associations of polymorphism with trait data were analyzed in 141 Junmu No. 1 individuals. Two vectors carried different 3′-UTR with 13bp insertion or deletion at site PS905, named pGL3-LUC-A and pGL3-LUC-B respectively, was constructed. Their effect on gene expression was analyzed in vitro by transient transfection of the individual reporter constructs into 3T3-l1 cells. The results are summarized as follows: 1) There is a polymorphic site in DGAT2 3′-UTR with 13bp fragment (TCCTCTGACCTGC) insertion or deletion; 2). Genotyping of PS905 polymorphic locus in Yorkshire, Landrace, Duroc, Lulai Black, Dapulian, Laiwu and Junmu No. 1 pigs shows that INS/INS is dominant in all these breeds;χ2 test indicates that all the populations tested were in a state of Hardy-Weinberg equilibrium and the frequency of allele A was higher in Chinese local pig breeds than in cultivated pig breeds and was the lowest in western breeds. 3). Association analysis on Junmu No. 1 data indicates that backfat thickness of individuals with genotype AA is significantly higher than AB individuals (P<0.01), and lean percentage of individuals with genotype AA is significantly higher than AB individuals (P<0.05). 4) In vitro study indicated that there is no significant difference in the activities of driving reporter gene transcription between pGL3-LUC-A and pGL3-LUC-B constructs (P =0.0672). 5) RNA structures predicted by Mfold show that secondary structure of 3′-UTR with 13bp insertion is more stable than deletion type.
Collectively, the present study shows that 13bp insertion is dominant on PS905 locus of DGAT2 3′-UTR in pigs. Association analysis indicates that allele A has higher backfat thickness and lower lean percentage. The transfection experiment with different 3′-UTR of reporter gene showed no significant differerces. The result that the activity of driving reporter gene transcription of pGL3-LUC-B is slightly higher is consistent with association analysis. Further studies need to be carried out to elucidate the effect of DGAT2 on fat deposition and pork quality.
引文
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