比较基因组学课件

比较基因组学ComparativeGenomics1Somewell-knownmodelorganismsEscherichiacoli—modelprokaryoteSaccharomycescerevisiae(baker’syeast)—modelunicellulareukaryoteCaenorhabditiselegans(nematode)—anexcellentmodelformulticellulardevelopmentalbiologyDrosophilamelanogaster(fruitfly)—modelinsectDaniorerio(zebrafish)—agoodmodelforvertebratedevelopmentalbiologyMusmusculus(mouse)—modelmammal,importantforthestudyofhumangenomeArabidopsisthaliana(thalecress)—modeldicotplantOryzasativa(rice)—modelcerealandmonocotplant

COLLEGEOFLIFESCIENCES2WhatthegenomesofmodelorganismstellusAlmosteveryhumangenehasacounterpartinthemouseandsomeblocksofDNAareprovingimpossibletotellapart3Humangenesmappedonto

mousechromosomes

4内容提要1、比较基因组学的定义和研究意义2、比较基因组学常用的基本概念3、比较基因组学研究的方法和相关研究4、相关研究论文简介

COLLEGEOFLIFESCIENCES51、比较基因组学定义及其研究意义：定义:比较基因组学是在基因组学水平上研究不同物种和品系之间在基因组结构与功能方面的亲源关系及其内在联系的一门新兴学科。研究意义

(1)指导在遗传与基因组信息较为缺乏的物种中进行基因的克隆和功能研究。

(2)通过研究生物进化过程中，基因组所发生的倍增、缺失、重组，对于生物进化研究，具有重大意义。

COLLEGEOFLIFESCIENCES6

Similarityvs.

Homology

(相似性与同源性)Similarity:

aphenomenonthatdifferentgenesorgenomesegmentsshowsimilarsequences.

Homology:

aphenomenonthatdifferentgenesorgenomesegmentshavethesameancestor.7相似性与同源性相似性(similarity)：

是指一种很直接的数量关系，比如部分相同或相似的百分比或其它一些合适的度量。同源性(homology)：指从一些数据中推断出的两个基因或蛋白质序列具有共同祖先的结论，属于质的判断。

COLLEGEOFLIFESCIENCE8Orthologvs.ParalogOrtholog（直向同源物）:homologousgenesorDNAsequencesindifferentgenomes(species)Paralog（横向同源物）:homologousgenesorDNAsequencesinthesamegenome(species)9paralogsorthologs

COLLEGEOFLIFESCIENCES10Colinearityvs.SyntenyColinearity:conservationofgenecontentandorderindifferentgenomes,whichisareflectionofhomologySynteny:conservedlinkageamonggenesindifferentgenomesregardlessofordermacrosyntenyvs.microsynteny1999Murphyetal.GenomeResearch199911共线性与同线性

共线性（Colinearity）在不同的基因组中基因和基因的排列顺序的一致性称为共线性，它反应了一种同源关系。同线性（synteny）

连锁的同源基因在不同物种基因组中有相同连锁关系。遗传图与物理图的共线性12

宏观共线性和微观共线性宏观共线性（macrosynteny）：指遗传连锁图上锚定标记排列次序的一致性。微观共线性(microsynteny)：是指物理图上基因顺序的一致排列。

COLLEGEOFLIFESCIENCE13ApproachesforgenomecomparisonGenomecomparisonistoidentifythehomologoussequencesamongdifferentgenomes.Twomethodscanbeusedforthispurpose:Hybridization-basedcomparison:usingSouthernhybridizationtoidentifyhomologoussequences.Sequence-basedcomparison:usingcomputertoidentifyhomologoussequences.14Hybridization-basedcomparisonUsethesamesetofDNAprobestolocateorthologsongeneticorphysicalmapsofdifferentspecieswiththemethodofSouthernblot,andthencomparetheorderoforthologsinthosespecies.Thecomparisonwillshowthemacro-colinearityamongthespeciesbeingtested.

COLLEGEOFLIFESCIENCES15PatternsofgenomecolinearityTheuseofthesamesetofmolecularmarkers(A–P)forgeneticmappingexperimentsindifferentspeciesallowsthealignmentoftheresultingchromosomemaps.Intheleftfigure,twochromosomemaps(Iand1)areshown,whicharecompletelycolinear.

COLLEGEOFLIFESCIENCES16Comparativemapsofthewheatgenomedescribedintermsofthericegenome(A)andtheAe.umbellulatagenome(B)

17Comparativegeneticmapsoffivegrassspecies:rice,foxtailmillet,sorghum,maizeandbarleyFivegrassgenomes,oneconsensusmap.

18Sequence-basedcomparisonComparisonofoverallstatisticsofnucleotidesequenceComparisonofcodingsequence(genes)Comparisonofsegmentalsequenceorwholegenome(genomealignment)

COLLEGEOFLIFESCIENCES19ComparisonofoverallnucleotidestatisticsComparisonofoverallnucleotidestatisticspresentaglobalviewofthesimilaritiesanddifferencesofthegenomes,including:genomesizeoverall(G+C)contentregionsofdifferent(G+C)contentgenomesignaturecodonusagebiasesaminoacidusagebiasestheratioofobserveddinucleotidefrequencyandtheexpectedfrequencygivenrandomnucleotidedistribution

COLLEGEOFLIFESCIENCE20ComparisonofgenesGenenumberGenehomologyGenecategoryGenestructureGenefunctionalrelationshipandinteraction

COLLEGEOFLIFESCIENCE21GenecomparisonprovidesapossiblewaytopredictgeneassociationandproteininteractionGeneassociation:Genesinvolvedinthesamemetabolicpathwaytendtoappeartogetherinagenome.Hence,byexaminingwhethertwogenesarecorrelatedinmanygenomes,itcouldbededucedthatthetwogenesmightbefunctionallyassociated.Proteininteraction:Iftwogenes(sayAandB)inseveralgenomesarefoundtohavebeenfusedinsomeothergenomes,itcouldbededucedthattheproteinscodedbygenesAandBmightinteracteitherfunctionallySequence-basedcomparisonorphysically.22物种间物理图距的保守性

禾本科类受体激酶LrK基因簇中的基因间距在大麦(A)、水稻(B)和玉米(C)中几乎完全相同，约为4—5kb，并保持很好的共线性。

COLLEGEOFLIFESCIENCE23GenomealignmentLongsequencealignmentisproblematicduetorearrangement.Presently,almostallofthealignmentalgorithmsfirstidentifylargeconservedsequenceelementsbetweenthetwogenomesequences,andthengeneratetheoverallalignment.Ingeneral,similargenomesmayresultinbetteralignment.

COLLEGEOFLIFESCIENCE24Alignmentbetweenthe4thchromosomesofindicarice

GLA4andjaponicariceNipponbareTheabovefigureshowsgoodglobalcolinearityonchromosome4betweenthetwosubspeciesofriceexceptforsomeindels.25Alignmentbetweenricechromosome4andfiveA.thalianachromosomesTheabovefigureshowsthatallthefiveArabidopsischromosomeshaveorthologsonricechromosome4.26Withingenomecomparisoncanrevealparalogous(duplicated)regionsTheleftfigureshowsthatmostoftheArabidopsisgenomesequenceisduplicated.Blockswiththesamecoloursrepresentparalogousregions.27Large-scaleduplicationsinplantgenomesThegenearrangementofaregionmappingtoA.thalianachromosome

1iscomparedtoitscounterpartonchromosome3.Genesincommontobothregionsareshownaswhiteboxes.Linesconnecthomologoussequences.Blackboxesrepresentgenesuniquetothechromosome1orchromosome3region,respectively.Thelocationofaboxrelativetothesequencedrawnasalineindicatesthedirectionoftranscription(Rossbergetal.,2001).

COLLEGEOFLIFESCIENCES28直系同源集簇(clustersoforthologousgroups，COG)

及其研究意义

直系同源集簇即指由1个共同的祖先基因衍生的1组基因，包括不同基因组中执行同一生物学功能的种间同源物(ortholog)，也包括同一基因组中因基因加倍产生的种内同源物(paralog)，或平行基因。直系同源集簇综合了比较基因组学、种系发生学和蛋白质分类学的信息，对预测新基因的功能具有重要意义。

COLLEGEOFLIFESCIENCES29Clusteroforthologousgenes(COG)Comparisonofgenesfromdifferentgenomescouldidentifyorthologousgenesandestablishtheclustersoforthologousgenes(COGs),whichusuallyrepresentclassesofmetabolicfunction.TheinformationofCOGrelationshipsandannotationscanbestoredindatabases.RelationshipbetweenseveralyeastandbacterialorthologsinNCBICOGdatabase

COLLEGEOFLIFESCIENCES30COGdatabasecanbeusedtopredictgenefunctions31思考题如何证明某一生物在进化过程中发生了全基因组的倍增事件而非个别基因的复制?

COLLEGEOFLIFESCIENCES32Thankyou!Questions?

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Comparativegenomicsofodorantandpheromonereceptorgenesinrodents

啮齿动物中气味和信息素受体基因的比较基因组学研究34气味受体基因

气味受体基因（主要嗅觉系统）对环境中的大多数挥发性化学物质进行识别并与不同的行为表现相联系,如寻找食物,反捕和标记领域等;

COLLEGEOFLIFESCIENCES35信息素受体基因信息素受体基因是由动物分泌的化学物质，用于影响同种动物的行为；是动物通过尿、粪便