Pairwise-Sequence-Alignment

PairwiseSequenceAlignment成对序列比对中国协和医科大学基础医学院2推荐读物‡DavidMount,2004.Bioinformatics,2nded.‡JonathenPavsner,2003.Bioinformatics&FunctionalGenomics‡生物信息学札记（）‡R.Durbinetal.BiologicalSequenceAnalysis3提纲‡序列比对的基本概念‡序列比对的基本方法‡动态规划算法的基本算法原理‡序列比对中的评分矩阵‡序列比对的统计分析‡利用NCBI的Blast2Seq进行成对序列比较4成对序列比对是最基本的生物信息学的计算‡用于确定两个蛋白质(或基因)结构或功能上是否相关‡用于识别蛋白质间共有的保守的domain‡是利用BLAST(下节内容)进行生物序列数据库搜索的基础‡用于基因组的分析‡用于蛋白质三维结构的预测‡……5Pairwisealignmentofhumanretinol-bindingproteinandβ-lactoglobulin1MKWVWALLLLAAWAAAERDCRVSSFRVKENFDKARFSGTWYAMAKKDPEG50RBP.||||.|...|:.||||.:|:1...MKCLLLALALTCGAQALIVT..QTMKGLDIQKVAGTWYSLAMAASD.44lactoglobulin51LFLQDNIVAEFSVDETGQMSATAKGRVR.LLNNWD..VCADMVGTFTDTE97RBP:||||::|.|.|||:|||.45ISLLDAQSAPLRV.YVEELKPTPEGDLEILLQKWENGECAQKKIIAEKTK93lactoglobulin98DPAKFKMKYWGVASFLQKGNDDHWIVDTDYDTYAV...........QYSC136RBP||||.|:.|||||..|94IPAVFKIDALNENKVL........VLDTDYKKYLLFCMENSAEPEQSLAC135lactoglobulin137RLLNLDGTCADSYSFVFSRDPNGLPPEAQKIVRQRQ.EELCLARQYRLIV185RBP.|||:||.||||136QCLVRTPEVDDEALEKFDKALKALPMHIRLSFNPTQLEEQCHI.......178lactoglobulin6RBPandb-lactoglobulinarehomologousproteinsthatsharerelatedthree-dimensionalstructuresretinol-bindingprotein(NP_006735)β-lactoglobulin(P02754)7Alignment‡Theprocessoflininguptwoormoresequencestoachievemaximallevelsofidentity(andconservation,inthecaseofaminoacidsequences)forthepurposeofassessingthedegreeofsimilarityandthepossibilityofhomology.‡Pairwisealignment(双重序列比对or成对序列比对)8几个重要概念(一)‡Homology(同源性)„Similarityattributedtodescentfromacommonancestor.‡Identity(相同性)„Theextenttowhichtwo(nucleotideoraminoacid)sequencesareinvariant.RBP26RVKENFDKARFSGTWYAMAKKDPEGLFLQDNIVAEFSVDETGQMSATAKGRVRLLNNWD-84+K+++++GTW++MA+L+AVT++L+W+glycodelin23QTKQDLELPKLAGTWHSMAMA-TNNISLMATLKAPLRVHITSLLPTPEDNLEIVLHRWEN81几个重要概念(二)‡Identity(相同性)„Theextenttowhichtwosequencesareinvariant‡Conservation(保守性)„Changesataspecificpositionofanaminoacidor(lesscommonly,DNA)sequencethatpreservethephysico-chemicalpropertiesoftheoriginalresidue.‡Similarity(相似性)„Theextenttowhichnucleotideorproteinsequencesarerelated.Itisbaseduponidentityplusconservation.10Pairwisealignmentofretinol-bindingproteinandb-lactoglobulin1MKWVWALLLLAAWAAAERDCRVSSFRVKENFDKARFSGTWYAMAKKDPEG50RBP.||||.|...|:.||||.:|:1...MKCLLLALALTCGAQALIVT..QTMKGLDIQKVAGTWYSLAMAASD.44lactoglobulin51LFLQDNIVAEFSVDETGQMSATAKGRVR.LLNNWD..VCADMVGTFTDTE97RBP:||||::|.|.|||:|||.45ISLLDAQSAPLRV.YVEELKPTPEGDLEILLQKWENGECAQKKIIAEKTK93lactoglobulin98DPAKFKMKYWGVASFLQKGNDDHWIVDTDYDTYAV...........QYSC136RBP||||.|:.|||||..|94IPAVFKIDALNENKVL........VLDTDYKKYLLFCMENSAEPEQSLAC135lactoglobulin137RLLNLDGTCADSYSFVFSRDPNGLPPEAQKIVRQRQ.EELCLARQYRLIV185RBP.|||:||.||||136QCLVRTPEVDDEALEKFDKALKALPMHIRLSFNPTQLEEQCHI.......178lactoglobulinIdentity(bar)以第一行为例：排列了44个氨基酸残基，11个相同，percentidentity为25%(11/44)11Pairwisealignmentofretinol-bindingproteinandb-lactoglobulin1MKWVWALLLLAAWAAAERDCRVSSFRVKENFDKARFSGTWYAMAKKDPEG50RBP.||||.|...|:.||||.:|:1...MKCLLLALALTCGAQALIVT..QTMKGLDIQKVAGTWYSLAMAASD.44lactoglobulin51LFLQDNIVAEFSVDETGQMSATAKGRVR.LLNNWD..VCADMVGTFTDTE97RBP:||||::|.|.|||:|||.45ISLLDAQSAPLRV.YVEELKPTPEGDLEILLQKWENGECAQKKIIAEKTK93lactoglobulin98DPAKFKMKYWGVASFLQKGNDDHWIVDTDYDTYAV...........QYSC136RBP||||.|:.|||||..|94IPAVFKIDALNENKVL........VLDTDYKKYLLFCMENSAEPEQSLAC135lactoglobulin137RLLNLDGTCADSYSFVFSRDPNGLPPEAQKIVRQRQ.EELCLARQYRLIV185RBP.|||:||.||||136QCLVRTPEVDDEALEKFDKALKALPMHIRLSFNPTQLEEQCHI.......178lactoglobulinSomewhatsimilar(onedot)Verysimilar(twodots)以第一行为例：排列了44个氨基酸残基，11个相同，3个相似，percentsimilarity为32%(14/44)12Pairwisealignmentofretinol-bindingproteinandb-lactoglobulin1MKWVWALLLLAAWAAAERDCRVSSFRVKENFDKARFSGTWYAMAKKDPEG50RBP.||||.|...|:.||||.:|:1...MKCLLLALALTCGAQALIVT..QTMKGLDIQKVAGTWYSLAMAASD.44lactoglobulin51LFLQDNIVAEFSVDETGQMSATAKGRVR.LLNNWD..VCADMVGTFTDTE97RBP:||||::|.|.|||:|||.45ISLLDAQSAPLRV.YVEELKPTPEGDLEILLQKWENGECAQKKIIAEKTK93lactoglobulin98DPAKFKMKYWGVASFLQKGNDDHWIVDTDYDTYAV...........QYSC136RBP||||.|:.|||||..|94IPAVFKIDALNENKVL........VLDTDYKKYLLFCMENSAEPEQSLAC135lactoglobulin137RLLNLDGTCADSYSFVFSRDPNGLPPEAQKIVRQRQ.EELCLARQYRLIV185RBP.|||:||.||||136QCLVRTPEVDDEALEKFDKALKALPMHIRLSFNPTQLEEQCHI.......178lactoglobulinInternalgapTerminalgapOpengapextensiongap13Gaps(空位)‡在序列比对中，在某一个位置如果一个残基没有匹配的残基，就形成空位；‡空位的评分分值常是负分（空位罚分）；‡因为单一一次突变事件会导致不止一个残基的插入或删除，因此在比对中空位的存在权重比空位长度的权重更大；‡在进行BLAST时,一般不需要改变缺省的空位罚分。1415几个重要概念(三)‡twotypesofhomologoussequence„Orthologs(直系同源类似物)‡Homologoussequencesindifferentspeciesthatarosefromacommonancestralgeneduringspeciation;„Paralogs(旁系同源类似物)‡Homologoussequenceswithinasinglespeciesthatarosebygeneduplication.16Homologoussequences.OrthologsandParalogsaretwotypesofhomologoussequences.Orthologydescribesgenesindifferentspeciesthatderivefromacommonancestor.Orthologousgenesmayormaynothavethesamefunction.Paralogydescribeshomologousgeneswithinasinglespeciesthatdivergedbygeneduplication.