大鼠基因组微卫星分布特征分析
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摘要
大鼠(Rattus norvegicus)是重要的生物模型动物,已被广泛应用于医学和药学研究。利用生物信息学方法对大鼠基因组外显子、基因间隔区以及内含子微卫星进行了搜索与分析,并对外显子微卫星所在的基因进行了定位,以及通过Blast2Go和KAAS程序进行功能分类注释。分析表明:(1)不同区域微卫星数量上,基因间隔区(1 104 149)>内含子(806 024)>外显子(4 665),外显子不同区域微卫星数量表现为CDS>3'UTR>5'UTR;(2)外显子中出现最多的重复拷贝类别是A,其次是AAG、AGC,三碱基和四碱基微卫星在外显子微卫星中最多,占56.7%;基因间隔区微卫星和内含子均以二碱基数量最多,两者出现最多重复拷贝类别均是AC,其次均是A、AG;(3)外显子区、基因间隔区和内含子区不同重复类型重复次数均以最小重复次数,微卫星数量最多;(4)外显子微卫星序列2 330条,位于1 203个基因上,GO注释表明涉及细胞成分(cellular component)占46.9%、生物过程(biological process)占39.3%和分子功能(molecular function)占13.8%;(5)KEGG通路分析表明,与人类疾病相关的基因最多(431),其次是参与机体系统相关的基因(387),和细胞过程相关基因最少(158)。本研究将为进一步分析大鼠微卫星功能及微卫星分子标记提供理论依据。
Rattus norvegicus is an important biological model animal, which has been widely used in biomedical and pharmaceutical research. Microsatellites(SSRs) of the exon, intergenic and intron regions of R. norvegicus genome were searched and analyzed by bioinformatics method. The SSRs of exon regions was located in genes and the functional annotation was performed by using procedures of Blast2Go and KAAS. The results were shown as follows:(1) the number of microsatellites in different regions, intergenic region(1 104 149) >intron(806 024) >exon(4 665), and CDS>3'UTR>5'UTR was presented in the exon regions as well;(2) the proportion of tri-and tetranucleotides in the exon regions was 56.7% and A was the most predominant, followed by AAG and AGC. The number of di-nucleotides was the most in either intergenic or intron regions, and AC were the most abundant,followed by A and AG;(3) the times of repetition for different repeat types in the exon, intergenic and intron regions were recorded with the minimum repetition number, and the number of microsatellites is the most;(4) there were 2 330 SSRs in the exon regions, located on 1 203 genes, and the GO annotation indicated that the cellular component was 46.9%, biological process was 39.3% and molecular function was 13.8%;(5) KEGG pathway analysis showed that the genes related to human diseases were the most(431), followed by the genes involved in the body system(387), and the genes related to cell processes were the least(158). This study would provide a theoretical basis for further analysis of microsatellite function and microsatellite molecular markers of Rattus norvegicus.
Rattus norvegicus is an important biological model animal, which has been widely used in biomedical and pharmaceutical research. Microsatellites(SSRs) of the exon, intergenic and intron regions of R. norvegicus genome were searched and analyzed by bioinformatics method. The SSRs of exon regions was located in genes and the functional annotation was performed by using procedures of Blast2Go and KAAS. The results were shown as follows:(1) the number of microsatellites in different regions, intergenic region(1 104 149) >intron(806 024) >exon(4 665), and CDS>3'UTR>5'UTR was presented in the exon regions as well;(2) the proportion of tri-and tetranucleotides in the exon regions was 56.7% and A was the most predominant, followed by AAG and AGC. The number of di-nucleotides was the most in either intergenic or intron regions, and AC were the most abundant,followed by A and AG;(3) the times of repetition for different repeat types in the exon, intergenic and intron regions were recorded with the minimum repetition number, and the number of microsatellites is the most;(4) there were 2 330 SSRs in the exon regions, located on 1 203 genes, and the GO annotation indicated that the cellular component was 46.9%, biological process was 39.3% and molecular function was 13.8%;(5) KEGG pathway analysis showed that the genes related to human diseases were the most(431), followed by the genes involved in the body system(387), and the genes related to cell processes were the least(158). This study would provide a theoretical basis for further analysis of microsatellite function and microsatellite molecular markers of Rattus norvegicus.
引文
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Conesa A.,Cotz S.,García-Gomez J.M.,Terol J.,Talon M.,and Robles M.,2005,Blast2Go:a universal tool for annotation,visualization and analysis in functional genomics research,Bioinformatics,21(18):3674-3676
Du L.,Li Y.,Zhang X.,and Yue B.,2013,MSDB:a user-friendly program for reporting distribution and building databases of microsatellites from genome sequences,Journal of Heredity,104(1):154-157
Du Y.R.,Tan C.M.,Xu Y.T.,Zhou Z.H.,Ma J.B.,and Guo S.C.,2016,Genome-wide characterization and identification of microsatellites in Pantholops hodgsoni,Sichuan Dongwu(Sichuan Journal of Zoology),35(6):845-851(都玉蓉,谭春敏,徐永涛,周智红,马建滨,郭松长,2016,藏羚羊基因组微卫星分析与初步验证,四川动物,35(6):845-851)
Ellegren H.,2004,Microsatellites:simple sequences with complex evolution,Nature Reviews Genetics,5(6):435-445
Hearne C.M.,Ghosh S.,and Todd J.A.,1992,Microsatellite for linkage and analysis of genetic traits,Trends in Genetics,8(8):288-294
Huang J.,Du L.M.,Li Y.Z.,Li Y.J.,Zhang X.Y.,and Yue B.S.,2012,Distribution regularities of microsatellites in the Gallus gallus genome,Sichuan Dongwu(Sichuan Journal of Zoology),31(3):358-363(黄杰,杜联明,李玉芝,李午佼,张修月,岳碧松,2012,红原鸡全基因组中微卫星分布规律研究,四川动物,31(3):358-363)
Huang J.,Li W.J.,Jian Z.Y.,Yue B.S.,and Yan Y.F.,2016,Genome-wide distribution and organization of microsatellites in six species of birds,Biochemical Systematics and E-cology,67:95-102
Huang J.,Li Y.Z.,Du L.M.,Yang B.,Shen F.J.,Zhang H.M.,Zhang Z.H.,Zhang X.Y.,and Yue B.S.,2015,Genome-wide survey and analysis of microsatellites in giant panda(Ailuropoda melanoleuca),with a focus on the applications of a novel microsatellite marker system,BMC Genomics,16(1):61
Labbe J.,Murat C.,Morin E.,Le Tacon F.,and Martin F.,2011,Survey and analysis of simple sequence repeats in the Laccaria bicolor genome,with development of microsatellite marker,Current Genetics,57(2):75-88
Lawson W.J.,and Zhang L.Q.,2006,Distinct patterns of SSR distribution in the Arabidopsis thaliana and rice genomes,Genome Biology,7(2):1-11
Leopoldino A.M.,and Pensa S.D.,2003,The mutational spectrum of human autosomal tetranucleotide microsatellites,Human Mutation,21(1):71-79
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):991-1007
Liu S.X.,Hou W.,Sun T.L.,Xu Y.T.,Li P.,Yue B.S.,and Li J.,2017,Genome-wide mining and comparative analysis of microsatellites in three macaque species,Molecular Genetics Genomics,292(3):537-550
Lu T.,Wang C.,Du C.,Liu S.,Sheng Y.M.,Zhang X.Y.,and Yue B.S.,2017,Distribution regularity of microsatellites in Moschus berezovskii genome,Sichuan Dongwu(Sichuan Journal of Zoology),36(4):420-424(卢婷,王晨,杜超,刘姝,沈咏梅,张修月,岳碧松,2017,林麝全基因组微卫星分布规律研究,四川动物,36(4):420-424)
Moriya Y.,Itoh M.,Okuda S.,Yoshizawa A.C.,and Kanehisa M.,2007,KAAS:an automatic genome annotation and pa仵hway reconstruction server,Nucleic Acids Research,35:182-185
Qi W.H.,Jiang X.M.,Du L.M.,Xiao G.S.,Hu T.Z.,Yue B.S.,and Quan Q.M.,2015,Genome-wide survey and analysis of microsatellite sequences in Bovid species,Plos One,10(7):1-17
Qi W.H.,Jiang X.M.,Xiao G.S.,and Huang X.Y.,2014,Distribution regularities of microsatellites in the pig genome,Xumu Yu Shouyi(Animal Husbandry&Veterinary Medicine),46(8):9-12(戚文华,蒋雪梅,肖国生,黄小云,2014,猪全基因组中微卫星分布规律,畜牧与兽医,46(8):9-12)
Qi W.H.,Jiang X.M.,Xiao G.S.,Huang X.Y.,and Du L.M.,2013,Seeking and bioinformati cs analysis of microsatellite sequence in the geno mes of cow and sheep,Xumu Shouyi Xuebao(Acta Veterinaria et Zootechnica Sinica),44(11):1724-1733(戚文华,蒋雪梅,肖国生,黄小云,杜联明,2013,牛和绵羊全基因组微卫星序列的搜索及其生物信息学分析,畜牧兽医学报,44(11):1724-1733)
Qian J.,Xu H.B.,Song J.Y.,Xu J.,Zhu Y.J.,and Chen S.L.,2013,Genome-wide analysis of simple sequence repeats in the model medicinal mushroom Ganoderma lucidum,Gene,512(2):331-336
Rhode C.,and Roodt-Wilding R.,2011,Bioinformatics survey of habitis midae microsatellites reveals a non-random distribution of repeat motifs,Biological Bulletin,221(2):147-154
Tong X.L.,Dai F.Y.,Li B.,Yu Q.Y.,Xia Q.Y.,and Lu C.,2006,Microsatellite repeats in mouse:abundance,distribution and density,Dongwu Xuebao(Acta Zoologica Sinica),52(1):138-152(童晓玲,代方银,李斌,余泉友,夏庆友,鲁成,2006,小鼠基因组中的微卫星重复序列的数量、分布和密度,动物学报,52(1):138-152)
Tu F.Y.,Liu X.H.,Du L.M.,Yan C.C.,and Huang X.F.,2015,Distribution characteristics of microsatellites in the rat genome,Jiangxi Nongye Daxue Xuebao(Acta Agriculturae Universitatis Jiangxiensis),37(4):708-711(涂飞云,刘晓华,杜联明,严超超,黄晓凤,2015,大鼠全基因组微卫星分布特征研究,江西农业大学学报,37(4):708-711)
Wang C.,Du L.M.,Li P.,Yang M.Y.,Li W.J.,Shen Y.M.,Zhang X.Y.,and Yue B.S.,2015,Distribution patterns of microsatellites in the genome of the German cockroach(Blattlla germanica),Kunchong Xuebao(Acta Entomologica Sinica),58(10):1037-1045(王晨,杜联明,李鹏,杨茗羽,李午佼,沈咏梅,张修月,岳碧松,2015,德国小蠊全基因组中微卫星分布规律,昆虫学报,58(10):1037-1045)
Wang X.T.,Zhang Y.J.,He X.,Mei T.,and Chen B.,2016,Identification,characteristics and distribution of microsatellites in the whole genome of Anopheles sinensis(Diptera:Culicidae),Kunchong Xuebao(Acta Entomologica Sinica),59(10):1058-1068(王小婷,张玉娟,何秀,梅婷,陈斌,2016,中华按蚊全基因组微卫星的鉴定特征及分布规律,昆虫学报,59(10):1058-1068)
Xu Y.T.,Hu Z.X.,Wang C.,Zhang X.Y.,Li J.,and Yue B.S.,2016,Characterization of perfect microsatellite based on genome-wide and chromosome level in Rhesus monkey(Macaca mulatta),Gene,592(2):269-275
Conesa A.,Cotz S.,García-Gomez J.M.,Terol J.,Talon M.,and Robles M.,2005,Blast2Go:a universal tool for annotation,visualization and analysis in functional genomics research,Bioinformatics,21(18):3674-3676
Du L.,Li Y.,Zhang X.,and Yue B.,2013,MSDB:a user-friendly program for reporting distribution and building databases of microsatellites from genome sequences,Journal of Heredity,104(1):154-157
Du Y.R.,Tan C.M.,Xu Y.T.,Zhou Z.H.,Ma J.B.,and Guo S.C.,2016,Genome-wide characterization and identification of microsatellites in Pantholops hodgsoni,Sichuan Dongwu(Sichuan Journal of Zoology),35(6):845-851(都玉蓉,谭春敏,徐永涛,周智红,马建滨,郭松长,2016,藏羚羊基因组微卫星分析与初步验证,四川动物,35(6):845-851)
Ellegren H.,2004,Microsatellites:simple sequences with complex evolution,Nature Reviews Genetics,5(6):435-445
Hearne C.M.,Ghosh S.,and Todd J.A.,1992,Microsatellite for linkage and analysis of genetic traits,Trends in Genetics,8(8):288-294
Huang J.,Du L.M.,Li Y.Z.,Li Y.J.,Zhang X.Y.,and Yue B.S.,2012,Distribution regularities of microsatellites in the Gallus gallus genome,Sichuan Dongwu(Sichuan Journal of Zoology),31(3):358-363(黄杰,杜联明,李玉芝,李午佼,张修月,岳碧松,2012,红原鸡全基因组中微卫星分布规律研究,四川动物,31(3):358-363)
Huang J.,Li W.J.,Jian Z.Y.,Yue B.S.,and Yan Y.F.,2016,Genome-wide distribution and organization of microsatellites in six species of birds,Biochemical Systematics and E-cology,67:95-102
Huang J.,Li Y.Z.,Du L.M.,Yang B.,Shen F.J.,Zhang H.M.,Zhang Z.H.,Zhang X.Y.,and Yue B.S.,2015,Genome-wide survey and analysis of microsatellites in giant panda(Ailuropoda melanoleuca),with a focus on the applications of a novel microsatellite marker system,BMC Genomics,16(1):61
Labbe J.,Murat C.,Morin E.,Le Tacon F.,and Martin F.,2011,Survey and analysis of simple sequence repeats in the Laccaria bicolor genome,with development of microsatellite marker,Current Genetics,57(2):75-88
Lawson W.J.,and Zhang L.Q.,2006,Distinct patterns of SSR distribution in the Arabidopsis thaliana and rice genomes,Genome Biology,7(2):1-11
Leopoldino A.M.,and Pensa S.D.,2003,The mutational spectrum of human autosomal tetranucleotide microsatellites,Human Mutation,21(1):71-79
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):991-1007
Liu S.X.,Hou W.,Sun T.L.,Xu Y.T.,Li P.,Yue B.S.,and Li J.,2017,Genome-wide mining and comparative analysis of microsatellites in three macaque species,Molecular Genetics Genomics,292(3):537-550
Lu T.,Wang C.,Du C.,Liu S.,Sheng Y.M.,Zhang X.Y.,and Yue B.S.,2017,Distribution regularity of microsatellites in Moschus berezovskii genome,Sichuan Dongwu(Sichuan Journal of Zoology),36(4):420-424(卢婷,王晨,杜超,刘姝,沈咏梅,张修月,岳碧松,2017,林麝全基因组微卫星分布规律研究,四川动物,36(4):420-424)
Moriya Y.,Itoh M.,Okuda S.,Yoshizawa A.C.,and Kanehisa M.,2007,KAAS:an automatic genome annotation and pa仵hway reconstruction server,Nucleic Acids Research,35:182-185
Qi W.H.,Jiang X.M.,Du L.M.,Xiao G.S.,Hu T.Z.,Yue B.S.,and Quan Q.M.,2015,Genome-wide survey and analysis of microsatellite sequences in Bovid species,Plos One,10(7):1-17
Qi W.H.,Jiang X.M.,Xiao G.S.,and Huang X.Y.,2014,Distribution regularities of microsatellites in the pig genome,Xumu Yu Shouyi(Animal Husbandry&Veterinary Medicine),46(8):9-12(戚文华,蒋雪梅,肖国生,黄小云,2014,猪全基因组中微卫星分布规律,畜牧与兽医,46(8):9-12)
Qi W.H.,Jiang X.M.,Xiao G.S.,Huang X.Y.,and Du L.M.,2013,Seeking and bioinformati cs analysis of microsatellite sequence in the geno mes of cow and sheep,Xumu Shouyi Xuebao(Acta Veterinaria et Zootechnica Sinica),44(11):1724-1733(戚文华,蒋雪梅,肖国生,黄小云,杜联明,2013,牛和绵羊全基因组微卫星序列的搜索及其生物信息学分析,畜牧兽医学报,44(11):1724-1733)
Qian J.,Xu H.B.,Song J.Y.,Xu J.,Zhu Y.J.,and Chen S.L.,2013,Genome-wide analysis of simple sequence repeats in the model medicinal mushroom Ganoderma lucidum,Gene,512(2):331-336
Rhode C.,and Roodt-Wilding R.,2011,Bioinformatics survey of habitis midae microsatellites reveals a non-random distribution of repeat motifs,Biological Bulletin,221(2):147-154
Tong X.L.,Dai F.Y.,Li B.,Yu Q.Y.,Xia Q.Y.,and Lu C.,2006,Microsatellite repeats in mouse:abundance,distribution and density,Dongwu Xuebao(Acta Zoologica Sinica),52(1):138-152(童晓玲,代方银,李斌,余泉友,夏庆友,鲁成,2006,小鼠基因组中的微卫星重复序列的数量、分布和密度,动物学报,52(1):138-152)
Tu F.Y.,Liu X.H.,Du L.M.,Yan C.C.,and Huang X.F.,2015,Distribution characteristics of microsatellites in the rat genome,Jiangxi Nongye Daxue Xuebao(Acta Agriculturae Universitatis Jiangxiensis),37(4):708-711(涂飞云,刘晓华,杜联明,严超超,黄晓凤,2015,大鼠全基因组微卫星分布特征研究,江西农业大学学报,37(4):708-711)
Wang C.,Du L.M.,Li P.,Yang M.Y.,Li W.J.,Shen Y.M.,Zhang X.Y.,and Yue B.S.,2015,Distribution patterns of microsatellites in the genome of the German cockroach(Blattlla germanica),Kunchong Xuebao(Acta Entomologica Sinica),58(10):1037-1045(王晨,杜联明,李鹏,杨茗羽,李午佼,沈咏梅,张修月,岳碧松,2015,德国小蠊全基因组中微卫星分布规律,昆虫学报,58(10):1037-1045)
Wang X.T.,Zhang Y.J.,He X.,Mei T.,and Chen B.,2016,Identification,characteristics and distribution of microsatellites in the whole genome of Anopheles sinensis(Diptera:Culicidae),Kunchong Xuebao(Acta Entomologica Sinica),59(10):1058-1068(王小婷,张玉娟,何秀,梅婷,陈斌,2016,中华按蚊全基因组微卫星的鉴定特征及分布规律,昆虫学报,59(10):1058-1068)
Xu Y.T.,Hu Z.X.,Wang C.,Zhang X.Y.,Li J.,and Yue B.S.,2016,Characterization of perfect microsatellite based on genome-wide and chromosome level in Rhesus monkey(Macaca mulatta),Gene,592(2):269-275