MYH3基因在动物肌肉发育、能量代谢及生产性能中的研究进展

doi:10.16431/j.cnki.1671-7236.2020.10.026

摘要/Abstract

摘要： 肌球蛋白重链3（myosin heavy chain 3，MYH3）基因编码胚胎型肌球蛋白重链蛋白，控制肌肉的牵引滑动。MYH3基因是肌肉分化的重要标志基因，能够调控肌肉发育及能量代谢，在动物整个肌肉发育过程中均发挥重要作用。MYH3基因在不同物种间高度保守，且在动物体内多组织中均有表达，在胚胎期肌肉组织和肌肉再生过程中表达量较高。它受转录因子、microRNA、lncRNA及环境营养因子等多种因素影响，也可调控其他基因的功能。MYH3基因突变可以改变TGF-β信号通路和MAPK信号通路相关蛋白的磷酸化水平；影响ATP酶活性，使ATP水解时间延长，延长横桥周期；影响肌肉的能量代谢，最终引发肌肉能量代谢疾病。MYH3基因拷贝数变化、突变或表达量变化与动物的体尺、胴体重、屠宰重、生长性能具有显著的相关性。MYH3基因在大理石花纹高、肌内脂肪高的肌肉组织中表达量高，被认为是影响动物肌肉嫩度、剪切力和肉色红度的重要候选基因。MYH3基因的高表达与骨骼肌中氧化Ⅰ型肌纤维的含量、肌纤维直径和慢肌纤维含量有关。作者介绍了MYH3基因的基本结构特点，指出了其与肌肉组织发育及相关影响因子之间的调控作用，阐述了MYH3基因与动物肌肉能量代谢、生长性能和肉品质之间的关系，为进一步研究MYH3基因与肌肉发育调控和肉质性能改良提供参考。

关键词: MYH3基因; 肌肉发育; 能量代谢; 生产性能

Abstract: Myosin heavy chain 3 (MYH3) gene encoded an embryonic myosin heavy chain protein that controlled the traction and sliding of muscles.MYH3 gene was an important marker gene for muscle differentiation,could regulated muscle development and energy metabolism,and played an important role in the entire muscle development of animals. MYH3 gene was highly conserved among different species and expressed in many tissues in animals,and it was highly expressed during embryonic muscle tissue and muscle regeneration.It was affected by various factors such as transcription factors,microRNA,lncRNA and environmental nutrition factors,and also regulated the funtion of other genes.MYH3 gene mutation could also change the phosphorylation level of TGF-β signaling pathway and MAPK signaling pathway related proteins.After mutation of MYH3 gene,it would affect the activity of ATPase,prolong the hydrolysis time of ATP and the cycle of transverse bridge,which could affect the energy metabolism of muscle and eventually lead to the disease of muscle energy metabolism.The change of copy number or expression level of MYH3 gene was significantly correlated with the size,carcass weight,slaughter weight and growth performance of animals.MYH3 gene was highly expressed in muscle tissues with high marbling and high intramuscular fat,and also to be considered an important candidate gene affecting muscle tenderness,shear strength and red flesh color of muscle in animals.The high expression of MYH3 gene was related to the content of oxidized type Ⅰ muscle fibers,diameter of muscle fibers and content of slow muscle fibers.This article introduced the basic structural characteristics of MYH3 gene,pointed out its regulatory role with muscle tissue development and related influencing factors,and then explained the relationship between MYH3 gene and animal muscle energy metabolism,growth performance and meat quality,which provided a reference for further research on MYH3 gene and muscle development regulation and meat quality improvement.

Key words: MYH3 gene; muscle development; energy metabolism; production performance

中图分类号:

Q789

代宇星, 盛志康, 楚菡, 刘哲, 陈月娥(Noppanun Poubol), 洪亮, 蒲蕾, 郭亮. MYH3基因在动物肌肉发育、能量代谢及生产性能中的研究进展[J]. 中国畜牧兽医, 2020, 47(10): 3270-3277.

DAI Yuxing, SHENG Zhikang, CHU Han, LIU Zhe, CHEN Yuee(Noppanun Poubol), HONG Liang, PU Lei, GUO Liang. Research Progress on MYH3 Gene in Animal Muscle Development, Energy Metabolism and Production Performance[J]. China Animal Husbandry and Veterinary Medicine, 2020, 47(10): 3270-3277.

参考文献 54

[1]	KNIGHT A E,MOLLOY J E.Muscle,myosin and single molecules[J].Essays in Biochemistry,2000,35:43-59.
[2]	SCHIAFFINO S.Fiber types in skeletal muscle:A personal account[J].Acta Physiologica,2010,199(4):451-463.
[3]	SANEYASU T,NAKANO Y,TSUCHII N,et al.Differential regulation of protein synthesis by skeletal muscle type in chickens[J].General and Comparative Endocrinology,2019,12(284):113246.
[4]	FOTH B J,GOEDECKE M C,SOLDATI D.New insights into myosin evolution and classification[J].Proceedings of the National Academy of Sciences,2006,103(10):3681-3686.
[5]	何一旻,顾鸣敏.肌球蛋白重链基因在人类遗传性疾病中的研究进展[J].遗传,2017,39(10):877-887. HE Y M,GU M M.Research progress of myosin heavy chain genes in human genetic diseases[J].Hereditas,2017,39(10):877-887.(in Chinese)
[6]	SUNG S S,BRASSINGTON A M,GRANNATT K,et al.Mutations in genes encoding fast-twitch contractile proteins cause distal arthrogryposis syndromes[J].American Journal of Human Genetics,2003,72(3):681-690.
[7]	HARI S B,PERERA B G K,RANJITKAR P,et al.Conformation-selective inhibitors reveal differences in the activation and phosphate-binding loops of the tyrosine kinases Abl and Src[J].ACS Chemical Biology,2013,8(12):2734-2743.
[8]	NICHOLAS J C,BORNA N,LIU Z W,et al.Analyses of the oncogenic BRAFD594G variant reveal a kinase-independent[J].The Journal of Biological Chemistry,2020,295(8):2407-2420.
[9]	SWETA M,MICHELLE S M,ROBERT O M,et al.Kinetic and structural analyses reveal residues in phosphoinositide 3-kinase that are critical for catalysis and substrate recognition[J].The Journal of Biological Chemistry,2017,292(33):13541-13550.
[10]	TERRY W H,LORETTA J H,WANG X,et al.A mutation in the converter subdomain of Aspergillus nidulans MyoB blocks constriction of the actomyosin ring in cytokinesis[J].Fungal Genetics and Biology,2015,75:72-83.
[11]	GIRISH C M,WILLIAM A K,ANJU M,et al.Interaction between the relay loop and the SH1-SH2 helix region in drosophila muscle myosin is essential for normal motor function,myofibril stability and muscle contraction[J].Biophysical Journal,2012,102(3):148a-149a.
[12]	DIPESH R,GOURINATH S,HIMMEL D M,et al.Myosin subfragment 1 structures reveal a partially bound nucleotide and a complex salt bridge that helps couple nucleotide and actin binding[J].Proceedings of the National Academy of Sciences of the United States of America,2004,101(27):8930-8935.
[13]	WANG L J,LIU X L,NIU F B,et al.Single nucleotide polymorphisms,haplotypes and combined genotypes in MYH3 gene and their associations with growth and carcass traits in Qinchuan cattle[J].Molecular Biology Reports,2013,40(1):417-426.
[14]	ZIEBA J,ZHANG W,CHONG J X,et al.A postnatal role for embryonic myosin revealed by MYH3 mutations that alter TGF-β signaling and cause autosomal dominant spondylocarpotarsal synostosis[J].Scientific Reports,2017,7:41803.
[15]	MARCELLO S,ANDREA A,ELISA DE G,et al.A novel pathogenic MYH3 mutation in a child with Sheldon-Hall syndrome and vertebral fusions[J].American Journal of Medical Genetics,2018,176(3):663-667.
[16]	TAJSHARGHI H,OLDFORS A.Myosinopathies:Pathology and mechanisms[J].Acta Neuropathologica,2013,125(1):3-18.
[17]	ACHARYYA S,LADNER K J,NELSEN L L,et al.Cancer cachexia is regulated by selective targeting of skeletal muscle gene products[J].Journal of Clinical Investigation,2004,114(3):370-378.
[18]	HASLETT J N,SANOUDOU D,BENNETT R R,et al.Gene expression comparison of biopsies from duchenne muscular dystrophy (DMD) and normal skeletal muscle[J].Proceedings of the National Acadeyny of Sciences of the United States of America,2002,99(23):15000-15005.
[19]	朱月.TCEA3对牛骨骼肌卫星细胞分化的影响[D].哈尔滨:东北农业大学,2017. ZHU Y.Impact of TCEA3 on bovine skeletal muscle satellite cell differentiation[D].Harbin:Northeast Agriculture University,2017.(in Chinese)
[20]	PEDROSA-DOMELLÖF F,HOLMGREN Y,LUCAS C A,et al.Human extraocular muscles:Unique pattern of myosin heavy chain expression during myotube formation[J].Invest Ophthalmol and Visual Science,2000,41(7):1608-1616.
[21]	CHO I C,PARK H B,AHN J S,et al.A functional regulatory variant of MYH3 influences muscle fiber-type composition and intramuscular fat content in pigs[J].PLoS Genetics,2019,15(10):8279.
[22]	ZHU Y,TONG H L,LI S F,et al.Effect of TCEA3 on the differentiation of bovine skeletal muscle satellite cells[J].Biochemical and Biophysical Research Communications,2017,484(4):827-832.
[23]	TONG H L,JIANG R Y,ZHANG W W,et al.miR-2425-5p targets RAD9A and MYOG to regulate the proliferation and differentiation of bovine skeletal muscle-derived satellite cells[J].Scientific Reports,2017,7(1):418.
[24]	ZHOU S,LI S,ZHANG W W,et al.miR-139 promotes differentiation of bovine skeletalmuscle-derived satellite cells by regulating DHFR gene expression[J].Journal of Cellular Physiology,2019,234(1):632-641.
[25]	CICHEWICZ M A,KIRAN M,PRZANOWSKA R K,et al.MUNC,an eRNA upstream from the MYOD gene,induces a subgroup of myogenic transcripts in trans,independently of MyoD[J].Molecular and Cellular Biology,2018,38(20):e00655-17.
[26]	MUELLER A C,CICHEWICZ M A,DEY B K,et al.MUNC,a long noncoding RNA that facilitates the function of MyoD in skeletal myogenesis[J].Molecular and Cellular Biology,2015,35:498-513.
[27]	VICTORIA C F,ERIN L B,YOSHITAKE C,et al.Ndrg2 is a PGC-1α/ERRα target gene that controls protein synthesis and expression of contractile-type genes in C2C12 myotubes[J].Biochimica et Biophysica Acta,2013,1833(12):3112-3123.
[28]	CHEN Z R,JIN G R,LIN S B,et al.DNA methyltransferase inhibitor CDA-II inhibits myogenic differentiation[J].Biochemical and Biophysical Research Communications,2012,422(3):522-526.
[29]	STEFANO S,ALBERTO C R,VIKA S,et al.Developmental myosins:Expression patterns and functional significance[J].Skeletal Muscle,2015,5(1):22.
[30]	ZHANG J,XU X,LIU Y,et al.EPA and DHA inhibit myogenesis and downregulate the expression of muscle-related genes in C2C12 myoblasts[J].Genes,2019,10(1):64.
[31]	OHASHI K,NAGATA Y,WADA E,et al.Zinc promotes proliferation and activation of myogenic cells via the PI3K/AKT and ERK signaling cascade[J].Experimental Cell Research,2015,333(2):228-37.
[32]	LIU S,GAO F,WEN L,et al.Osteocalcin induces proliferation via positive activation of the PI3K/AKT,P38 MAPK pathways and promotes differentiation through activation of the LI GPRC6A-ERK1/2 pathway in C2C12 myoblast cells[J].Cellular Physiology and Biochemistry,2017,43(3):1100-1112.
[33]	FU Y Y,LI S,TONG H L,et al.WDR13 promotes the differentiation of bovine skeletal muscle-derived satellite cells by affecting PI3K/AKT signaling[J].Cell Biology International,2019,43(7):799-808.
[34]	邵为.MYH3基因突变在先天性脊柱畸形发病中的作用及机制研究[D].上海:中国人民解放军海军军医大学,2019. SHAO W.The role and mechanism of MYH3 gene mutation in the pathogenesis of congenital vertebral malformation[D].Shanghai:The Second Military Medical University,2019.(in Chinese)
[35]	MARTI-MARIMON M,VIALANEIX N,VOILLET V,et al.A new approach of gene co-expression network inference reveals significant biological processes involved in porcine muscle development in late gestation[J].Scientific Reports,2018,8(1):10150.
[36]	WALKLATE J,VERA C,BLOEMINK M J,et al.The most prevalent freeman-sheldon syndrome mutations in the embryonic myosin motor share functional defects[J].The Journal of Biological Chemistry,2016,291(19):10318-10331.
[37]	SHREYASI D,PANKAJ K,AAKANKSHA V,et al.Myosin heavy chain mutations that cause Freeman-Sheldon syndrome lead to muscle structural and functional defects in Drosophila[J].Developmental Biology,2019,449(2):90-98.
[38]	BAMSHAD M,JORDE L B,CAREY J C.A revised and extended classification of the distal arthrogryposes[J].American Journal of Medical Genetics Part,1996,65(4):277-281.
[39]	XU Y,KANG Q L,ZHANG Z L.A MYH3 mutation identified for the first time in a Chinese family with Sheldon-Hall syndrome(DA2B)[J].Neuromuscular Disorders,2018,28(5):456-462.
[40]	RACCA A W,BECK A E,MCMILLIN M J,et al.The embryonic myosin R672C mutation that underlies Freeman-Sheldon syndrome impairs cross-bridge detachment and cycling in adult skeletal muscle[J].Human Molecular Genetics,2015,24(12):3348-3358.
[41]	MASAKI T,SATOSHI S,RYUJI F,et al.A novel truncating mutation in MYH3 causes spondylocarpotarsal synostosis syndrome with basilar invagination[J].Journal of Human Genetics,2018,63(12):1277-1281.
[42]	王丽君.秦川牛生长与胴体性状相关候选基因的表达谱、遗传多样性及其关联分析[D].杨凌:西北农林科技大学,2013. WANG L J.Expression patterns,genetic diversity and correlation analysis with related traits of candidate genes in Qinchuan cattle[D].Yangling:Northwest A&F University,2013.(in Chinese)
[43]	徐瑶.黄牛全基因组分析及肌肉发育相关基因剂量效应研究[D].杨凌:西北农林科技大学,2014. XU Y.Whole genome analysis of Chinese cattle and the dosage effects of the skeletal muscle involving genes[D].Yangling:Northwest A&F University,2014.(in Chinese)
[44]	XU Y,SHI T,CAI H F,et al.Associations of MYH3 gene copy number variations with transcriptional expression and growth traits in Chinese cattle[J].Gene,2014,535(2):106-111.
[45]	CLARK D L,BOLER D D,KUTZLER L W,et al.Muscle gene expression associated with increased marbling in beef cattle[J].Animal Biotechnology,2011,22(2):51-63.
[46]	ZHAO C P,TIAN F,YU Y,et al.Muscle transcriptomic analyses in Angus cattle with divergent tenderness[J].Molecular Biology Reports,2012,39(4):4185-4193.
[47]	程笃学.猪肉质性状的全基因组关联研究[D].北京:中国农业科学院,2012. CHENG D X.Genome-wide association study for meat trait in swine[D].Beijing:Chinese Academy of Agricultural Sciences,2012.(in Chinese)
[48]	李娜.基于GWAS的猪肉品质性状候选基因研究[D].北京:中国农业大学,2016. LI N.Genome-wide association studies for pig meat traits and exploration of major genes[D].Beijing:China Agricultural University,2016.(in Chinese)
[49]	LI X,KIM S W,DO K T,et al.Analyses of porcine public SNPs in coding-gene regions by re-sequencing and phenotypic association studies[J].Molecular Biology Reports,2011,38(6):3805-3820.
[50]	XIONG X W,LIU X X,ZHOU L S,et al.Genome-wide association analysis reveals genetic loci and candidate genes for meat quality traits in Chinese Laiwu pigs[J].Mammalian Genome,2015,26(3-4):181-190.
[51]	成志敏,张宁芳,王媛媛,等.基于RNA-Seq技术筛选影响猪肌纤维性状的候选基因[J].畜牧兽医学报,2019,50(5):918-929. CHENG Z M,ZHANG N F,WANG Y Y,et al.Screening of candidate genes for muscle fiber characteristics in pig using RNA-Seq[J].Chinese Journal of Animal and Veterinary Sciences,2019,50(5):918-929.(in Chinese)
[52]	REHFELDT C,FIEDLER I,DIETL G,et al.Myogenesis and postnatal skeletal muscle cell growth as influenced by selection[J].Livestock Production Science,2000,66(2):177-188.
[53]	CHOE J H,CHOI Y M,LEE S H,et al.The relation between glycogen,lactate content and muscle fiber type composition,and their influence on postmortem glycolytic rate and pork quality[J].Meat Science,2008,80(2):355-362.
[54]	CHOI Y M,RYU Y C,KIM B C.Influence of myosin heavy-and light chain isoforms on early postmortem glycolytic rate and pork quality[J].Meat Science,2007,76(2):281-288.