比较基因组学ppt课件.ppt

1、1Escherichia coli model prokaryoteSaccharomyces cerevisiae (bakers yeast) model unicellular eukaryoteCaenorhabditis elegans (nematode) an excellent model for multicellular developmental biologyDrosophila melanogaster (fruit fly) model insectDanio rerio (zebrafish) a good model for vertebrate develop

2、mental 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 SCIENCES2Almost every human gene has a counterpart in the mouse and some blocks of DNA are p

3、roving impossible to tell apart341、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 SCIENCES5 1、比较基因组学定义及其研究意义：、比较基因组学定义及其研究意义：定义定义:比较基因组学是在基因组学水平上研究不同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。关系及其内在联系的一门新兴学科。研究意义研究意义 (1) 指导在遗传与基因组信息较为缺乏的物种

4、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 SCIENCES6Similarity:Similarity: a phenomenon that different genes or genome segments show similar sequences. Homology:Homology: a phenomenon that different genes or genome segments have the same ancestor.7相似性相似性(simil

5、arity)： 是指一种很直接的数量关系数量关系，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，属于质的判断质的判断。 COLLEGE OF LIFE SCIENCE8Ortholog（直向同源物）（直向同源物）: homologous genes or DNA sequences in different genomes (species)Paralog（横向同源物）（横向同源物）: homologous genes or DNA sequences in the same genome (s

6、pecies)9paralogsorthologs COLLEGE OF LIFE SCIENCES10Colinearity: conservation of gene content and order in different genomes, which is a reflection of homologySynteny: conserved linkage among genes in different genomes regardless of order macrosynteny vs. microsyntenymacrosynteny vs. microsynteny199

7、9Murphy et al. Genome Research 199911 共线性（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（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遗传图与物理图的共线性12宏观共线性（宏观共线性（macrosyntenymacrosynteny） ：指遗传连锁图上锚定标记排列次序的一致性。指遗传连锁图上锚定标记排列次序的一致性。微观共线性微观共线性(microsynteny) (microsynteny) ：是指物理图上基因顺序的一致排列。是

8、指物理图上基因顺序的一致排列。 COLLEGE OF LIFE SCIENCE13Genome 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 identify homologous sequences. Sequence-based comparison: using comput

9、er to identify homologous sequences.14Use 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 orthologs in those species.The comparison will show the macro-colinearity among the species being

10、tested. COLLEGE OF LIFE SCIENCES15The use of the same set of molecular markers (AP) for genetic mapping experiments in different species allows the alignment of the resulting chromosome maps. In the left figure, two chromosome maps (I and 1) are shown, which are completely colinear. COLLEGE OF LIFE

11、SCIENCES1617Five grass genomes, one consensus map. 18Comparison of overall statistics of nucleotide sequenceComparison of coding sequence (genes)Comparison of segmental sequence or whole genome (genome alignment) COLLEGE OF LIFE SCIENCES19Comparison of overall nucleotide statistics present a global

12、view of the similarities and differences of the genomes, including: genome size overall (G+C) content regions of different (G+C) content genome signature codon usage biases amino acid usage biases the ratio of observed dinucleotide frequency and the expected frequency given random nucleotide distrib

13、ution COLLEGE OF LIFE SCIENCE20Gene numberGene homologyGene categoryGene structureGene functional relationship and interaction COLLEGE OF LIFE SCIENCE21Gene association: Genes involved in the same metabolic pathway tend to appear together in a genome. Hence, by examining whether two genes are correl

14、ated in many genomes, it could be deduced that the two genes might be 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 fun

15、ctionally Sequence-based comparison or physically.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45 kb，并保持很好的共线性。 COLLEGE OF LIFE SCIENCE23Long sequence alignment is problematic due to rearrangement. Presently, almost all of the alignment algorithms first identify large conserved sequ

16、ence elements between the two genome sequences, and then generate the overall alignment. In general, similar genomes may result in better alignment. COLLEGE OF LIFE SCIENCE24The above figure shows good global colinearity on chromosome 4 between the two subspecies of rice except for some indels.25The

17、 above figure shows that all the five Arabidopsis chromosomes have orthologs on rice chromosome 4.26The left figure shows that most of the Arabidopsis genome sequence is duplicated. Blocks with the same colours represent paralogous regions.27The gene arrangement of a region mapping to A. thaliana ch

18、romosome 1 is compared to its counterpart on chromosome 3. Genes in common 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 a

19、s a line indicates the direction of transcription (Rossberg et al., 2001). COLLEGE OF LIFE SCIENCES28直系同源集簇直系同源集簇(clusters of orthologous groups，COG) 及其研究意义及其研究意义 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

20、的功能具有重要意义。 COLLEGE OF LIFE SCIENCES29Comparison 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 databas

21、es.Relationship between several yeast and bacterial orthologs in NCBI COG database COLLEGE OF LIFE SCIENCES3031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 SCIENCES3233Comparative genomics of odorant and pheromone receptor genes in rodents 啮齿动物中气味和信息素啮齿动物中气味和信息素 受体基因的比较基因组学研究受体基因的比较基因组学研究34

22、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,如寻找寻找食物食物, ,反捕和标记领反捕和标记领域域等; COLLEGE OF LIFE SCIENCES35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 SCIENCES36 Applied a comprehensive data-mining strategy to examine the repertoires 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 SCIENCES37 COLLEGE OF LIFE SCIENCES3839 COLLEGE OF LIFE SCIENCES404142 COLLEGE OF LIFE SCIENCES4344