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1、比较基因组学Comparative Genomics,1,Some well-known model organisms,Escherichia coli model prokaryoteSaccharomyces cerevisiae (bakers yeast) model unicellular eukaryoteCaenorhabditis elegans (nematode) an excellent model for multicellular developmental biologyDrosophila melanogaster (fruit fly) model insec
2、tDanio rerio (zebrafish) a good model for vertebrate developmental biologyMus musculus (mouse) model mammal, important for the study of human genomeArabidopsis thaliana (thale cress ) model dicot plantOryza sativa (rice) model cereal and monocot plant,COLLEGE OF LIFE SCIENCES,2,What the genomes of m
3、odel organisms tell us,Almost every human gene has a counterpart in the mouse and some blocks of DNA are proving impossible to tell apart,3,Human genes mapped onto mouse chromosomes,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,COLLEGE OF LIFE SCIENCES,5,1、比较基因组学定义及其研究意义：定义:比较基因
4、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。,COLLEGE OF LIFE SCIENCES,6,Similarity vs. Homology (相似性与同源性),Similarity: a phenomenon that different genes or genome segments show similar sequences. Homo
5、logy: a phenomenon that different genes or genome segments have the same ancestor.,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。,COLLEGE OF LIFE SCIENCE,8,Ortholog vs. Paralog,Ortholog（直向同源物）: homologous genes or DNA sequences i
6、n different genomes (species)Paralog（横向同源物）: homologous genes or DNA sequences in the same genome (species),9,paralogs,orthologs,COLLEGE OF LIFE SCIENCES,10,Colinearity vs. Synteny,Colinearity: conservation of gene content and order in different genomes, which is a reflection of homologySynteny: con
7、served linkage among genes in different genomes regardless of order macrosynteny vs. microsynteny,1999,Murphy et al. Genome Research 1999,11,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
8、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。,COLLEGE OF LIFE SCIENCE,13,Approaches for genome comparison,Genome comparison is to identify the homologous sequences among different genomes. Two methods can be used for this purpose:Hybridization-based comparison: using Southern hybridization to ide
9、ntify homologous sequences.Sequence-based comparison: using computer to identify homologous sequences.,14,Hybridization-based comparison,Use the same set of DNA probes to locate orthologs on genetic or physical maps of different species with the method of Southern blot, and then compare the order of
10、 orthologs in those species.The comparison will show the macro-colinearity among the species being tested.,COLLEGE OF LIFE SCIENCES,15,Patterns of genome colinearity,The use of the same set of molecular markers (AP) for genetic mapping experiments in different species allows the alignment of the res
11、ulting chromosome maps. In the left figure, two chromosome maps (I and 1) are shown, which are completely colinear.,COLLEGE OF LIFE SCIENCES,16,Comparative maps of the wheat genome described in terms of the rice genome (A) and the Ae. umbellulata genome (B),17,Comparative genetic maps of five grass
12、species: rice, foxtail millet, sorghum, maize and barley,Five grass genomes, one consensus map.,18,Sequence-based comparison,Comparison of overall statistics of nucleotide sequenceComparison of coding sequence (genes)Comparison of segmental sequence or whole genome (genome alignment),COLLEGE OF LIFE
13、 SCIENCES,19,Comparison of overall nucleotide statistics,Comparison of overall nucleotide statistics present a global view of the similarities and differences of the genomes, including:genome size overall (G+C) content regions of different (G+C) contentgenome signaturecodon usage biases amino acid u
14、sage biases the ratio of observed dinucleotide frequency and the expected frequency given random nucleotide distribution,COLLEGE OF LIFE SCIENCE,20,Comparison of genes,Gene numberGene homologyGene categoryGene structureGene functional relationship and interaction,COLLEGE OF LIFE SCIENCE,21,Gene comp
15、arison provides a possible way to predict gene association and protein interaction,Gene association: Genes involved in the same metabolic pathway tend to appear together in a genome. Hence, by examining whether two genes are correlated in many genomes, it could be deduced that the two genes might be
16、 functionally associated. Protein interaction: If two genes (say A and B) in several genomes are found to have been fused in some other genomes, it could be deduced that the proteins coded by genes A and B might interact either functionally Sequence-based comparison or physically.,22,物种间物理图距的保守性 禾本科
17、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45 kb，并保持很好的共线性。,COLLEGE OF LIFE SCIENCE,23,Genome alignment,Long sequence alignment is problematic due to rearrangement. Presently, almost all of the alignment algorithms first identify large conserved sequence elements between the two genome sequences,
18、and then generate the overall alignment. In general, similar genomes may result in better alignment.,COLLEGE OF LIFE SCIENCE,24,Alignment between the 4th chromosomes of indica rice GLA4 and japonica rice Nipponbare,The above figure shows good global colinearity on chromosome 4 between the two subspe
19、cies of rice except for some indels.,25,Alignment between rice chromosome 4 and five A. thaliana chromosomes,The above figure shows that all the five Arabidopsis chromosomes have orthologs on rice chromosome 4.,26,Within genome comparison can reveal paralogous (duplicated) regions,The left figure sh
20、ows that most of the Arabidopsis genome sequence is duplicated. Blocks with the same colours represent paralogous regions.,27,Large-scale duplications in plant genomes,The gene arrangement of a region mapping to A. thaliana chromosome 1 is compared to its counterpart on chromosome 3. Genes in common
21、 to both regions are shown as white boxes. Lines connect homologous sequences. Black boxes represent genes unique to the chromosome 1 or chromosome 3 region, respectively. The location of a box relative to the sequence drawn as a line indicates the direction of transcription (Rossberg et al., 2001).
22、,COLLEGE OF LIFE SCIENCES,28,直系同源集簇(clusters of orthologous groups，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。,COLLEGE OF LIFE SCIENCES,29,Cluster of orthologous genes (COG),Comparison
23、 of genes from different genomes could identify orthologous genes and establish the clusters of orthologous genes (COGs), which usually represent classes of metabolic function.The information of COG relationships and annotations can be stored in databases.,Relationship between several yeast and bact
24、erial orthologs in NCBI COG database,COLLEGE OF LIFE SCIENCES,30,COG database can be used to predict gene functions,31,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?,COLLEGE OF LIFE SCIENCES,32,Thank you ! Questions?,33,Comparative genomics of odorant and pheromone receptor genes in rodents 啮齿动物中气味和信息素 受体
25、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;,COLLEGE OF LIFE SCIENCES,35,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、粪便或特化的皮肤腺释放到体外的一种或几种化学物质的混合。,COLLEGE OF LIFE SCIENCES,36,Material and Methods,Applied a comprehensive data-mining strategy to examine the repe
26、rtoires of rat and mouse odorant receptors (ORs) and type 1 pheromone receptors (V1Rs) using mouse and rat genomesData miningPhylogenetic analysisSimilarity comparisonMotif discovery,COLLEGE OF LIFE SCIENCES,We applied a comprehensive data-mining strategy to examine the repertoires of rat and mouse
27、odorant receptors (ORs) and type 1 pheromonereceptors (V1Rs) using the mm5 (mouse) and rn3 (rat) genomes.,37,COLLEGE OF LIFE SCIENCES,38,39,COLLEGE OF LIFE SCIENCES,40,Comparison of rodent ORs and V1Rs through phylogenetic analysis.,41,Similarity analysis of OR/V1R genes.,42,Motif analysis of OR and V1R sequences.,COLLEGE OF LIFE SCIENCES,43,Thank you ! Questions?,44,
