埃博拉病毒基因组中微卫星序列的分布分析
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摘要
微卫星或简单重复序列(simple sequence repeat, SSR)在真核和原核生物以及病毒基因组中普遍存在,并被广泛用于遗传与进化研究。本研究从NCBI中下载埃博拉病毒属的四个不同种的埃博拉病毒全基因组序列,筛选36条作为实验材料,利用IMEx在线提取软件提取SSRs,用Python编程统计数据,从而分析SSRs在埃博拉病毒全基因组序列中的分布情况。分析得出,埃博拉病毒基因组序列中二型SSRs含量最为丰富,其次是一型SSRs,三型SSRs有少量,四型SSRs则更少,没有发现五型和六型SSRs。在更深入的分析中得出在埃博拉病毒属四个种中,含A/T碱基的SSRs含量远远大于含C/G碱基的SSRs。分析得出一型SSRs中(A)n/(T)n远多于(G)n/(C)n,二型SSRs中不存在(GC/CG)n,三型中也不存在(GGC/CGG/GCG/CCG/CGC/GCC) n。上述发现可能跟埃博拉病毒的致病机理有密切联系。通过对埃博拉病毒基因组序列中SSRs的分析,为研究埃博拉病毒的变异情况及致病机制提供更多参考。
Microsatellites or Simple Sequence Repeat,(SSR) are ubiquitous in prokaryotic organism, eukaryotic organism, and viral genome, which have been extensively used for heredity and evolutionary studies. In this study,36 complete genomic sequences of Ebolavirus from 4 species were selected in National Center for Biotechnology Information(NCBI), and SSRs were extracted from these samples through an online extraction software IMEx with statistical work in Python, to analyze of the distribution of SSRs in complete genomes of Ebolavirus. The results showed the content of dinucleotide SSRs(di-SSRs) was the most abundant SSRs in genomic sequences of Ebolavirus, followed by mononucleotide SSRs(mono-SSRs), trinucleotide SSRs(tri-SSRs) and tetranucleotide SSRs(tetra-SSRs), but pentanucleotide SSRs(penta-SSRs) and hexnucleotide SSRs(hex-SSRs) had not been found. Further analysis showed that in 4 species of genus Ebolavirus, the SSRs containing A/T nucleotide had been detected to be more than the SSRs containing C/G nucleotide. The content of(A)n and(T)n in mononucleotide SSRs were much more higher than the content of(G)n and(C)n. There was no(GC/CG)n discovered in dinucleotide SSRs, and also no(GGC/CGG/GCG/CCG/CGC/GCC) n discovered in trinucleotide SSRs. Those discoveries might be closely related to the pathogenic mechanism of the Ebolavirus. By analyzing the SSRs in the genomes of Ebolavirus, this analysis could provide more reference to study the mutation and pathogenic mechanism of the Ebolavirus.
Microsatellites or Simple Sequence Repeat,(SSR) are ubiquitous in prokaryotic organism, eukaryotic organism, and viral genome, which have been extensively used for heredity and evolutionary studies. In this study,36 complete genomic sequences of Ebolavirus from 4 species were selected in National Center for Biotechnology Information(NCBI), and SSRs were extracted from these samples through an online extraction software IMEx with statistical work in Python, to analyze of the distribution of SSRs in complete genomes of Ebolavirus. The results showed the content of dinucleotide SSRs(di-SSRs) was the most abundant SSRs in genomic sequences of Ebolavirus, followed by mononucleotide SSRs(mono-SSRs), trinucleotide SSRs(tri-SSRs) and tetranucleotide SSRs(tetra-SSRs), but pentanucleotide SSRs(penta-SSRs) and hexnucleotide SSRs(hex-SSRs) had not been found. Further analysis showed that in 4 species of genus Ebolavirus, the SSRs containing A/T nucleotide had been detected to be more than the SSRs containing C/G nucleotide. The content of(A)n and(T)n in mononucleotide SSRs were much more higher than the content of(G)n and(C)n. There was no(GC/CG)n discovered in dinucleotide SSRs, and also no(GGC/CGG/GCG/CCG/CGC/GCC) n discovered in trinucleotide SSRs. Those discoveries might be closely related to the pathogenic mechanism of the Ebolavirus. By analyzing the SSRs in the genomes of Ebolavirus, this analysis could provide more reference to study the mutation and pathogenic mechanism of the Ebolavirus.
引文
Alam C.M.,Singh A.K.,Sharfuddin C.,and Ali S.,2013,In-silico analysis of simple and imperfect microsatellites in diverse tobamovirus genomes,Gene,53(2):193
Alam C.M.,Singh A.K.,Sharfuddin C.,and Ali S.,2014a,Genomewide scan for analysis of simple and imperfect microsatellites in diverse carlaviruses,Infection Genetics and Evolution Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases,21C(1):287
Alam C.M.,Singh A.K.,Sharfuddin C.,and Ali S.,2014b,Incidence,complexity and diversity of simple sequence repeats across potexvirus genomes,Gene,537(2):189
Bacolla A.,Larson J.E.,Collins J.R.,Milosavljevic A.,Stenson P.D.,Cooper D.N.,and Wells R.D.,2008,Abundance and length of simple repeats in vertebrate genomes are determined by their structural properties,Genome Research,18(10):1545-1553
Dettman J.R.,and Taylor J.W.,2004,Mutation and evolution of microsatellite loci in neurospora,Genetics,168(3):1231-1248
Diehl W.E.,Lin A.E.,Grubaungh N.D.,Carvalho L.M.,Kim K.,Kyawe P.P.,McCauley S.M.,Donnard E.,Kucukural A.,McDonel P.,Schaffner S.F.,Garber M.,Rambaut A.,Andersen K.G.,Sabeti P.C.,and Luban J.,2016,Ebolavirus glycoprotein with increased infectivity dominated the 2013-2016epidemic,Cell,167(4):1088
Ellegren H.,2004,Microsatellites:simple sequences with complex evolution,Nature Reviews Genetics,5(6):435-445
Han Z.,Boshra H.,Sunyer J.O.,Zwiers S.H.,Paragas J.,and Harty R.N.,2003,Biochemical and functional characterization of the Ebolavirus vp24 protein:implications for a role in virus assembly and budding,Journal of Virology,77(3):1793
Jurka J.,and Pethiyagoda C.,1995,Simple repetitive DNA sequences from primates:compilation and analysis,Journal of Molecular Evolution,40(2):120
King A.M.Q.,Carstens E.B.,and Lefkowitz E.J.,2012,Ninth report of the international committee on taxonomy of viruses,Elsevier,(9):653-671
Kruglyak S.,Durrett R.T.,Schug M.D.,and Aquadro C.F.,1998,Equilibrium distributions of microsatellite repeat length resulting from a balance between slippage events and point mutations,Proceedings of the National Academy of Sciences of the United States of America,95(18):10774-10778
Lai Y.,and Sun F.,2003,The relationship between microsatellite slippage mutation rate and the number of repeat units,Molecular Biology and Evolution,20(12):2123-2131
Li Y.C.,Korol A.B.,Fahima T.,and Nevo E.,2004,Microsatellites within genes:structure,function and evolution,Molecular Biology and Evolution,21(6):991
Mrázek J.,2006,Analysis of distribution indicates diverse functions of simple sequence repeats in mycoplasma genomes,Molecular Biology and Evolution,23(7):1370-1385
Oestereich L.,Lüdtke A.,Wurr S.,Rieger T.,Mu觡ozfontela C.,and Günther S.,2014,Successful treatment of advanced E-bolavirus infection with t-705(favipiravir)in a small animal model,Antiviral Research,105(1):17-21
Singh A.K.,Alam C.M.,Sharfuddin C.,and Ali S.,2014,Frequency and distribution of simple and compound microsatellites in forty-eight human papillomavirus(hpv)genomes,Infection Genetics and Evolution Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases,24(2):92-98
Tong Y.,Shi W.,Liu D.,Qian J.,Liang L.,and Bo X.,2015,Erratum:genetic diversity and evolutionary dynamics of E-bolavirus in sierra leone,Nature,524(7563):1-11
Toth G.,and Gaspari Z.J.,2000,Microsatellites in different eukaryotic genomes:survey and analysis,Genome Research,10(7):967
Urbanowicz R.A.,Mcclure C.P.,Sakuntabhai A.,Sall A.A.,Kob inger G.,and Müller M.A.,Holmes E.C.,Rey F.A.,Simon-Lo riere E.,and Ball J.K.,2016,Human adaptation of Ebolavirus during the west african outbreak,Cell,167(4):1079-1087
Wierdl M.,Dominska M.,and Petes T.D.,1997,Microsatellite instability in yeast:dependence on the length of the microsatel lite,Genetics,146(3):769
Zhao X.,Tan Z.,Feng H.,Yang R.,Li M.,and Jiang J.,Shen G.,and Yu R.,2011,Microsatellites in different potyvirus,genomes:survey and analysis,Gene,488(1-2):52-56
Zhao X.,Tian Y.,Yang R.,Feng H.,Ouyang Q.,You T.,Tan Z.,Li M.,Niu Y.,Jiang J.,Shen G.,and Yu R.,2012,Coevolu tion between simple sequence repeats(ssrs)and virus genome size,Bmc Genomics,13(1):435
Zhou L.,Deng L.,Fu Y.,Wu X.,Zhao X.,and Chen Y.,2016,Comparative analysis of microsatellites and compound microsatellites in t4-like viruses,Gene,575(2):695-701
Alam C.M.,Singh A.K.,Sharfuddin C.,and Ali S.,2014a,Genomewide scan for analysis of simple and imperfect microsatellites in diverse carlaviruses,Infection Genetics and Evolution Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases,21C(1):287
Alam C.M.,Singh A.K.,Sharfuddin C.,and Ali S.,2014b,Incidence,complexity and diversity of simple sequence repeats across potexvirus genomes,Gene,537(2):189
Bacolla A.,Larson J.E.,Collins J.R.,Milosavljevic A.,Stenson P.D.,Cooper D.N.,and Wells R.D.,2008,Abundance and length of simple repeats in vertebrate genomes are determined by their structural properties,Genome Research,18(10):1545-1553
Dettman J.R.,and Taylor J.W.,2004,Mutation and evolution of microsatellite loci in neurospora,Genetics,168(3):1231-1248
Diehl W.E.,Lin A.E.,Grubaungh N.D.,Carvalho L.M.,Kim K.,Kyawe P.P.,McCauley S.M.,Donnard E.,Kucukural A.,McDonel P.,Schaffner S.F.,Garber M.,Rambaut A.,Andersen K.G.,Sabeti P.C.,and Luban J.,2016,Ebolavirus glycoprotein with increased infectivity dominated the 2013-2016epidemic,Cell,167(4):1088
Ellegren H.,2004,Microsatellites:simple sequences with complex evolution,Nature Reviews Genetics,5(6):435-445
Han Z.,Boshra H.,Sunyer J.O.,Zwiers S.H.,Paragas J.,and Harty R.N.,2003,Biochemical and functional characterization of the Ebolavirus vp24 protein:implications for a role in virus assembly and budding,Journal of Virology,77(3):1793
Jurka J.,and Pethiyagoda C.,1995,Simple repetitive DNA sequences from primates:compilation and analysis,Journal of Molecular Evolution,40(2):120
King A.M.Q.,Carstens E.B.,and Lefkowitz E.J.,2012,Ninth report of the international committee on taxonomy of viruses,Elsevier,(9):653-671
Kruglyak S.,Durrett R.T.,Schug M.D.,and Aquadro C.F.,1998,Equilibrium distributions of microsatellite repeat length resulting from a balance between slippage events and point mutations,Proceedings of the National Academy of Sciences of the United States of America,95(18):10774-10778
Lai Y.,and Sun F.,2003,The relationship between microsatellite slippage mutation rate and the number of repeat units,Molecular Biology and Evolution,20(12):2123-2131
Li Y.C.,Korol A.B.,Fahima T.,and Nevo E.,2004,Microsatellites within genes:structure,function and evolution,Molecular Biology and Evolution,21(6):991
Mrázek J.,2006,Analysis of distribution indicates diverse functions of simple sequence repeats in mycoplasma genomes,Molecular Biology and Evolution,23(7):1370-1385
Oestereich L.,Lüdtke A.,Wurr S.,Rieger T.,Mu觡ozfontela C.,and Günther S.,2014,Successful treatment of advanced E-bolavirus infection with t-705(favipiravir)in a small animal model,Antiviral Research,105(1):17-21
Singh A.K.,Alam C.M.,Sharfuddin C.,and Ali S.,2014,Frequency and distribution of simple and compound microsatellites in forty-eight human papillomavirus(hpv)genomes,Infection Genetics and Evolution Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases,24(2):92-98
Tong Y.,Shi W.,Liu D.,Qian J.,Liang L.,and Bo X.,2015,Erratum:genetic diversity and evolutionary dynamics of E-bolavirus in sierra leone,Nature,524(7563):1-11
Toth G.,and Gaspari Z.J.,2000,Microsatellites in different eukaryotic genomes:survey and analysis,Genome Research,10(7):967
Urbanowicz R.A.,Mcclure C.P.,Sakuntabhai A.,Sall A.A.,Kob inger G.,and Müller M.A.,Holmes E.C.,Rey F.A.,Simon-Lo riere E.,and Ball J.K.,2016,Human adaptation of Ebolavirus during the west african outbreak,Cell,167(4):1079-1087
Wierdl M.,Dominska M.,and Petes T.D.,1997,Microsatellite instability in yeast:dependence on the length of the microsatel lite,Genetics,146(3):769
Zhao X.,Tan Z.,Feng H.,Yang R.,Li M.,and Jiang J.,Shen G.,and Yu R.,2011,Microsatellites in different potyvirus,genomes:survey and analysis,Gene,488(1-2):52-56
Zhao X.,Tian Y.,Yang R.,Feng H.,Ouyang Q.,You T.,Tan Z.,Li M.,Niu Y.,Jiang J.,Shen G.,and Yu R.,2012,Coevolu tion between simple sequence repeats(ssrs)and virus genome size,Bmc Genomics,13(1):435
Zhou L.,Deng L.,Fu Y.,Wu X.,Zhao X.,and Chen Y.,2016,Comparative analysis of microsatellites and compound microsatellites in t4-like viruses,Gene,575(2):695-701