人类基因组碱基组成的统计研究
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摘要
Chargaff第一和第二匹配规则构成了DNA双螺旋配对模型和单链上碱基数量关系的理论基石。在我们的研究中,我们对整个人类基因组进行了统计分析,引入了对称性的方法考察不同长度的碱基多联体(从2联体到6联体)和单个的碱基在各条染色体上的分布规律,对各种对称性在人类基因组中的表现形式进行了研究。在对人类基因组进行统计对称性考察的同时,还将各染色体的碱基组成与一条在单个碱基水平上按照Chargaff第二匹配规则生成的随机序列进行了对比分析。我们发现人类基因组在整体上遵守Chargaff第二匹配规则,具有镜像互补对称性。但是在局部范围内,人类基因组表现出了一定程度的对Chargaff第二匹配规则的背离,我们观察到在人类基因组中随着DNA序列长度的不断增大,它对Chargaff第二匹配规则背离就越小。同时,人类染色体与随机序列相比所表现出来的碱基分布不一致性,以及所具有的对称性不一致性,说明了在人类基因组中所表现出来的Chargaff第二匹配规则并不是由于人类染色体上所含碱基数量巨大而出现的统计现象,它的出现是基因组长期进化的结果。
The first thing to study human genome is to figure out the statistical properties of base composition. In this paper we have studied human genome for the frequencies of occurrence of mononucleotides and oligonucleotides (from dinucleotides to hexnucleotides), and made a research to the form of the performance of the various symmetries in the human genome. Furthermore, then we have compared the statistical features of human genome to an artificial random sequence generated according to Chargaff's second parity rule in mononucleotide level. We found that the human genome would comply with the Chargaff's second parity rule, put another way, it possessed the mirror complementary symmetry. And local deviation has been observed in human chromosomes, and as the length of DNA segment, we observed increases the deviation to Chargaff's second parity rule would decrease to a small extent. Human genome follows Chargaff's second parity rule in large scale, nevertheless, the occurrence of oligonucleotides frequencies in human chromosomes differ with random sequences, and the symmetry inconsistency between them had shown that the obedience to Chargaff's second parity rule for human genome shouldn't be a subsequence of mathematics since the human chromosome sequences are of too long.
The first thing to study human genome is to figure out the statistical properties of base composition. In this paper we have studied human genome for the frequencies of occurrence of mononucleotides and oligonucleotides (from dinucleotides to hexnucleotides), and made a research to the form of the performance of the various symmetries in the human genome. Furthermore, then we have compared the statistical features of human genome to an artificial random sequence generated according to Chargaff's second parity rule in mononucleotide level. We found that the human genome would comply with the Chargaff's second parity rule, put another way, it possessed the mirror complementary symmetry. And local deviation has been observed in human chromosomes, and as the length of DNA segment, we observed increases the deviation to Chargaff's second parity rule would decrease to a small extent. Human genome follows Chargaff's second parity rule in large scale, nevertheless, the occurrence of oligonucleotides frequencies in human chromosomes differ with random sequences, and the symmetry inconsistency between them had shown that the obedience to Chargaff's second parity rule for human genome shouldn't be a subsequence of mathematics since the human chromosome sequences are of too long.
引文
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[24]李晓哲,李霞,郭政.基因组信息学及有关的分子生物学数据库[J].数理医药学杂志.1999(04).
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[30]Prabhu V V.Symmetry observations in long nucleotide sequences.[J].Nucleic Acids Res.1993,21(12):2797-2800.
[31]Lobry J R.Properties of a general model of DNA evolution under no-strand-bias conditions.[J].J Mol Evol.1995,40(3):326-330.
[32]Sueoka N.Intrastrand parity rules of DNA base composition and usage biases of synonymous codons.[J].J Mol Evol.1995,40(3):318-325.
[33]Qi D,Cuticchia A J.Compositional symmetries in complete genomes.[J].Bioinformatics.2001,17(6):557-559.
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[35]Zhang C T,Zhang R.A nucleotide composition constraint of genome sequences.[J].Comput Biol Chem.2004,28(2):149-153.
[36]Smithies O,Engels W R,Devereux J R,et al.Base substitutions,length differences and DNA strand asymmetries in the human G gamma and A gamma fetal globin gene region.[J].Cell.1981,26(3 Pt 1):345-353.
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[38]Mitchell D.GC content and genome length in Chargaff compliant genomes.[J].Biochem Biophys Res Commun.2007,353(1):207-210.
[39]Chargaff E.Essays on Nucleic Acids[M].Elsevier,1963:211.
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[41]Szybalski W,Bovre K,Fiandt M,et al.Transcriptional controls in developing bacteriophages.[J].J Cell Physiol.1969,74(2):133-170.
[42]Chargaff E.How genetics got a chemical education.[J].Ann N Y Acad Sci.1979,325:344-360.
[43]Sueoka N.Compositional correlation between deoxyribonucleic acid and protein.[J].Cold Spring Harb Syrup Quant Biol.1961,26:35-43.
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[49]刘新星,李红燕,杨英杰.MATLAB 7.X生物信息工具箱的应用--基因序列分析(一)[J].现代生物医学进展.2008(01).
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[51]常世杰,尹勇,龙哲,et al.Matlab在生物信息分析中的应用前景[J].生物医学工程研究.2006(03).
[52]刘俏,张雪飞,权春善,et al.用MATLAB生物信息学工具箱分析人类线粒体基因序列[J].计算机与应用化学.2005(09).
[53]姜运良.卫星、小卫星和微卫星DNA--真核生物基因组的串状重复序列[J].生命的化学.1998(03).
[54]Ta布朗.基因组2[M].科学出版社,2006.
[55]Bissler J J.Triplex DNA and human disease.[J].Front Biosci.2007,12:4536-4546.
[56]Lang D M.Imperfect DNA mirror repeats in the gag gene of HIV-1(HXB2)identify key functional domains and coincide with protein structural elements in each of the mature proteins.[J].Virol J.2007,4:113.
[57]Mirkin S M,Lyamichev V I,Drushlyak K N,et al.DNA H form requires a homopurine-homopyrimidine mirror repeat.[J].Nature.1987,330(6147):495-497.
[58]Lillo F,Spano M.Inverted and mirror repeats in model nucleotide sequences.[J].Phys Rev E Star Nonlin Soft Matter Phys.2007,76(4 Pt 1):041914.
[59]Blaszak R T,Potaman V,Sinden R R,et al.DNA structural transitions within the PKDI gene.[J].Nucleic Acids Res.1999,27(13):2610-2617.
[60]Patel H P,Lu L,Blaszak R T,et al.PKD1 intron 21:triplex DNA formation and effect on replication.[J].Nucleic Acids Res.2004,32(4):1460-1468.
[61]Forsdyke D R,Mortimer J R.Chargaffs legacy.[J].Gene.2000,261(1):127-137.
[62] Albrecht-buehler G. Asymptotically increasing compliance of genomes with Chargaff s second parity rules through inversions and inverted transpositions. [J]. Proc Natl Acad Sci U S A. 2006, 103(47): 17828-17833.
[63] Frank A C, Lobry J R. Asymmetric substitution patterns: a review of possible underlying mutational or selective mechanisms.[J]. Gene. 1999, 238(1): 65-77.
[64] Lobry J R, Lobry C. Evolution of DNA base composition under no-strand-bias conditions when the substitution rates are not constant.[J]. Mol Biol Evol. 1999,16(6): 719-723.
[65] Okamura K, Wei J, Scherer S W. Evolutionary implications of inversions that have caused intra-strand parity in DNA.[J]. BMC Genomics. 2007, 8:160.
[2]人类基因组计划的内容[J].生命科学仪器.2003(06).
[3]刘济.“大科学”计划之一--人类基因组计划[J].科学之友.2004(10).
[4]鲍智娟.人类基因组计划的内容与研究方法[J].白城师范学院学报.2006(04).
[5]李志翔.人类基因组计划的综述[J].中学生物学.2007(04).
[6]于军.“人类基因组”计划与健康[J].养生大世界.2006(10).
[7]基因组医学、染色体组和人类疾病基因(1)[J].现代临床医学生物工程学杂志.2004(01).
[8]基因组医学、染色体组和人类疾病基因(2)[J].现代临床医学生物工程学杂志.2004(02).
[9]基因组医学、染色体组和人类疾病基因(3)[J].现代临床医学生物工程学杂志.2004(03).
[10]张猛,于军.人类基因组计划对人类健康的深远影响[J].中国优生优育.2007(01).
[11]张猛,于军.人类基因组计划与人类健康[J].医学研究杂志.2007(05).
[12]Dunham I,Shimizu N,Roe B A,et al.The DNA sequence of human chromosome 22.[J].Nature.1999,402(6761):489-495.
[13]Gregory S G,Barlow K F,Mclay K E,et al.The DNA sequence and biological annotation of human chromosome 1.[J].Nature.2006,441(7091):315-321.
[14]郝柏林.生物信息学[J].中国科学院院刊.2000(04).
[15]林金安.生物信息学简介[J].生物学教学.2000(07).
[16]许东.生物信息学与计算机科学[J].计算机教育.2006:41-43.
[17]朱庆华,李亮.生物信息学:我们能做什么?[J],情报理论与实践.2006,29(4):419-422.
[18]郝鲁江,梁泉峰.生物信息学的发展及其应用[J].山东轻工业学院学报.2000(02).
[19]张立人.试论生物信息学在生命科学中的意义[J].浙江中医学院学报.2000(01).
[20]张阳德.生物信息学(1):概论[J].外科理论与实践.2006(05).
[21]王正华,王勇献.后基因组时代生物信息学的新进展[J].国防科技大学学报.2003(01).
[22]谌琛.基因组信息学--现状和前景[J].中国分子心脏病学杂志.2003(05).
[23]吴诗光.基因组信息学[J].生物学通报.2001(09).
[24]李晓哲,李霞,郭政.基因组信息学及有关的分子生物学数据库[J].数理医药学杂志.1999(04).
[25]张晓东,张传富,彭科峰,et al.生物信息学数据库研究进展[J].生物信息学.2006,4(3):143-145.
[26]姜鑫.生物信息学数据库及其利用方法[J].现代情报.2005,25(6):185-187.
[27]吴诗光,任雪平.基因组信息学[J].周口师范高等专科学校学报.2001(02).
[28]Chargaff E.Structure and function of nucleic acids as cell constituents.[J].Fed Proc.1951,10(3):654-659.
[29]Watson J D,Crick F H.Molecular structure of nucleic acids;a structure for deoxyribose nucleic acid.[J].Nature.1953,171(4356):737-738.
[30]Prabhu V V.Symmetry observations in long nucleotide sequences.[J].Nucleic Acids Res.1993,21(12):2797-2800.
[31]Lobry J R.Properties of a general model of DNA evolution under no-strand-bias conditions.[J].J Mol Evol.1995,40(3):326-330.
[32]Sueoka N.Intrastrand parity rules of DNA base composition and usage biases of synonymous codons.[J].J Mol Evol.1995,40(3):318-325.
[33]Qi D,Cuticchia A J.Compositional symmetries in complete genomes.[J].Bioinformatics.2001,17(6):557-559.
[34]Mitchell D,Bridge R.A test of Chargaffs second rule.[J].Biochem Biophys Res Commun.2006,340(1): 90-94.
[35]Zhang C T,Zhang R.A nucleotide composition constraint of genome sequences.[J].Comput Biol Chem.2004,28(2):149-153.
[36]Smithies O,Engels W R,Devereux J R,et al.Base substitutions,length differences and DNA strand asymmetries in the human G gamma and A gamma fetal globin gene region.[J].Cell.1981,26(3 Pt 1):345-353.
[37]Nikolaou C,Almirantis Y.Deviations from Chargaffs second parity rule in organellar DNA Insights into the evolution of organellar genomes.[J].Gene.2006,381:34-41.
[38]Mitchell D.GC content and genome length in Chargaff compliant genomes.[J].Biochem Biophys Res Commun.2007,353(1):207-210.
[39]Chargaff E.Essays on Nucleic Acids[M].Elsevier,1963:211.
[40]Szybaiski W,Kubinski H,Sheldrick P.Pyrimidine clusters on the transcribing strand of DNA and their possible role in the initiation of RNA synthesis.[J].Cold Spring Harb Symp Quant Biol.1966,31:123-127.
[41]Szybalski W,Bovre K,Fiandt M,et al.Transcriptional controls in developing bacteriophages.[J].J Cell Physiol.1969,74(2):133-170.
[42]Chargaff E.How genetics got a chemical education.[J].Ann N Y Acad Sci.1979,325:344-360.
[43]Sueoka N.Compositional correlation between deoxyribonucleic acid and protein.[J].Cold Spring Harb Syrup Quant Biol.1961,26:35-43.
[44]吕兰兰,刘忠.MATLAB软件的功能特点[J].中国电化教育.2003(02).
[45]段天英.MATLAB软件的应用与开发[J].中国原子能科学研究院年报.1999(00).
[46]张宪起.Matlab软件在科研生产中的应用[J].集成电路通讯.2006(03).
[47]飞思科技产品研发中心.MATLAB 7基础与提高[M].电子工业出版社,2005.
[48]杨建强,罗先香.MATLAB软件工具箱简介[J].水科学进展.2001(02).
[49]刘新星,李红燕,杨英杰.MATLAB 7.X生物信息工具箱的应用--基因序列分析(一)[J].现代生物医学进展.2008(01).
[50]李红燕,刘新星,谢建平,et al.MATLAB 7.X生物信息工具箱的应用--序列比对(二)[J].现代生物医学进展.2008(02).
[51]常世杰,尹勇,龙哲,et al.Matlab在生物信息分析中的应用前景[J].生物医学工程研究.2006(03).
[52]刘俏,张雪飞,权春善,et al.用MATLAB生物信息学工具箱分析人类线粒体基因序列[J].计算机与应用化学.2005(09).
[53]姜运良.卫星、小卫星和微卫星DNA--真核生物基因组的串状重复序列[J].生命的化学.1998(03).
[54]Ta布朗.基因组2[M].科学出版社,2006.
[55]Bissler J J.Triplex DNA and human disease.[J].Front Biosci.2007,12:4536-4546.
[56]Lang D M.Imperfect DNA mirror repeats in the gag gene of HIV-1(HXB2)identify key functional domains and coincide with protein structural elements in each of the mature proteins.[J].Virol J.2007,4:113.
[57]Mirkin S M,Lyamichev V I,Drushlyak K N,et al.DNA H form requires a homopurine-homopyrimidine mirror repeat.[J].Nature.1987,330(6147):495-497.
[58]Lillo F,Spano M.Inverted and mirror repeats in model nucleotide sequences.[J].Phys Rev E Star Nonlin Soft Matter Phys.2007,76(4 Pt 1):041914.
[59]Blaszak R T,Potaman V,Sinden R R,et al.DNA structural transitions within the PKDI gene.[J].Nucleic Acids Res.1999,27(13):2610-2617.
[60]Patel H P,Lu L,Blaszak R T,et al.PKD1 intron 21:triplex DNA formation and effect on replication.[J].Nucleic Acids Res.2004,32(4):1460-1468.
[61]Forsdyke D R,Mortimer J R.Chargaffs legacy.[J].Gene.2000,261(1):127-137.
[62] Albrecht-buehler G. Asymptotically increasing compliance of genomes with Chargaff s second parity rules through inversions and inverted transpositions. [J]. Proc Natl Acad Sci U S A. 2006, 103(47): 17828-17833.
[63] Frank A C, Lobry J R. Asymmetric substitution patterns: a review of possible underlying mutational or selective mechanisms.[J]. Gene. 1999, 238(1): 65-77.
[64] Lobry J R, Lobry C. Evolution of DNA base composition under no-strand-bias conditions when the substitution rates are not constant.[J]. Mol Biol Evol. 1999,16(6): 719-723.
[65] Okamura K, Wei J, Scherer S W. Evolutionary implications of inversions that have caused intra-strand parity in DNA.[J]. BMC Genomics. 2007, 8:160.