比較基因組學7-1

1、Xiaofang Xie E-mail:Some well-known model organismsEscherichia coli model prokaryoteSaccharomyces cerevisiae (bakers yeast) model unicellular eukaryoteCaenorhabditis elegans (nematode) an excellent model for multicellular developmental biologyDrosophila melanogaster (fruit fly) model insectDanio rer

2、io (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 SCIENCESWhat the genomes of model organism

3、s tell usAlmost every human gene has a counterpart in the mouse and some blocks of DNA are proving impossible to tell apartHuman genes mapped onto mouse chromosomes內(nèi)容提要內(nèi)容提要 1、比較基因組學的定義和研究意義 2、比較基因組學常用的基本概念 3、比較基因組學研究的方法和相關(guān)研究 4、相關(guān)研究論文簡介 COLLEGE OF LIFE SCIENCES 1、比較基因組學定義及其研究意義：、比較基因組學定義及其研究意義：定義定義:比

4、較基因組學是在基因組學水平上研究不同比較基因組學是在基因組學水平上研究不同物種和品系之間在基因組結(jié)構(gòu)與功能方面的親源物種和品系之間在基因組結(jié)構(gòu)與功能方面的親源關(guān)系及其內(nèi)在聯(lián)系的一門新興學科。關(guān)系及其內(nèi)在聯(lián)系的一門新興學科。研究意義研究意義 (1) 指導在遺傳與基因組信息較為缺乏的物種中 進行基因的克隆和功能研究。 (2) 通過研究生物進化過程中，基因組所發(fā)生的 倍增、缺失、重組，對于生物進化研究，具 有重大意義。 COLLEGE OF LIFE SCIENCES Similarity vs. Homology (相似性與同源性相似性與同源性) Similarity: a phenomenon

5、that different genes or genome segments show similar sequences. Homology: a phenomenon that different genes or genome segments have the same ancestor.相似性與同源性相似性與同源性相似性相似性(similarity)： 是指一種很直接的數(shù)量關(guān)系數(shù)量關(guān)系，比如部分相同或相似的百分比或其它一些合適的度量。同源性同源性(homology)： 指從一些數(shù)據(jù)中推斷出的兩個基因或蛋白質(zhì)序列具有共同祖先的結(jié)論，屬于質(zhì)的判斷質(zhì)的判斷。 COLLEGE OF LIF

6、E SCIENCEOrtholog vs. Paralog Ortholog（直向同源物）（直向同源物）: homologous genes or DNA sequences in different genomes (species) Paralog（橫向同源物）（橫向同源物）: homologous genes or DNA sequences in the same genome (species)paralogsorthologs COLLEGE OF LIFE SCIENCESColinearity vs. Synteny Colinearity: conservation of g

7、ene content and order in different genomes, which is a reflection of homology Synteny: conserved linkage among genes in different genomes regardless of order macrosynteny vs. microsynteny1999Murphy et al. Genome Research 1999共線性與同線性共線性與同線性 共線性（共線性（Colinearity）在不同的基因組中基因和基因的排列順序的一致性稱為共線性，它反應(yīng)了一種同源關(guān)系。

8、同線性（同線性（synteny） 連鎖的同源基因在不同物種基因組中有相同連鎖關(guān)系。遺傳圖與物理圖的共線性遺傳圖與物理圖的共線性 宏觀共線性和微觀共線性宏觀共線性和微觀共線性 宏觀共線性（宏觀共線性（macrosynteny） ： 指遺傳連鎖圖上錨定標記排列次序的一致性。指遺傳連鎖圖上錨定標記排列次序的一致性。 微觀共線性微觀共線性(microsynteny) ： 是指物理圖上基因順序的一致排列。是指物理圖上基因順序的一致排列。 COLLEGE OF LIFE SCIENCEApproaches for genome comparison Genome comparison is to iden

9、tify 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 computer to identify homologous sequences.Hybridization-based comparison Us

10、e 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 tested. COLLEGE OF LIFE SCIENCESPattern

11、s of genome colinearityThe 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 SCIENCESCom

12、parative maps of the wheat genome described in terms of the rice genome (A) and the Ae. umbellulata genome (B) Comparative genetic maps of five grass species: rice, foxtail millet, sorghum, maize and barleyFive grass genomes, one consensus map. Sequence-based comparison Comparison of overall statist

13、ics of nucleotide sequence Comparison of coding sequence (genes) Comparison of segmental sequence or whole genome (genome alignment) COLLEGE OF LIFE SCIENCESComparison of overall nucleotide statistics Comparison of overall nucleotide statistics present a global view of the similarities and differenc

14、es 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 distribution COLLEGE OF LIFE SCIENCECompariso

15、n of genes Gene number Gene homology Gene category Gene structure Gene functional relationship and interaction COLLEGE OF LIFE SCIENCEGene comparison provides a possible way to predict gene association and protein interactionGene association: Genes involved in the same metabolic pathway tend to appe

16、ar 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 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 d

17、educed that the proteins coded by genes A and B might interact either functionally Sequence-based comparison or physically.物種間物理圖距的保守性 禾本科類受體激酶LrK基因簇中的基因間距在大麥(A)、水稻(B)和玉米(C)中幾乎完全相同，約為45 kb，并保持很好的共線性。 COLLEGE OF LIFE SCIENCEGenome alignmentLong sequence alignment is problematic due to rearrangement.

18、Presently, almost all of the alignment algorithms first identify large conserved sequence elements between the two genome sequences, and then generate the overall alignment. In general, similar genomes may result in better alignment. COLLEGE OF LIFE SCIENCEAlignment between the 4th chromosomes of in

19、dica rice GLA4 and japonica rice NipponbareThe above figure shows good global colinearity on chromosome 4 between the two subspecies of rice except for some indels.Alignment between rice chromosome 4 and five A. thaliana chromosomesThe above figure shows that all the five Arabidopsis chromosomes hav

20、e orthologs on rice chromosome 4.Within genome comparison can reveal paralogous (duplicated) regionsThe left figure shows that most of the Arabidopsis genome sequence is duplicated. Blocks with the same colours represent paralogous regions.Large-scale duplications in plant genomesThe gene arrangemen

21、t of a region mapping to A. thaliana chromosome 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

22、 a box relative to the sequence drawn as a line indicates the direction of transcription (Rossberg et al., 2001). COLLEGE OF LIFE SCIENCES直系同源集簇直系同源集簇(clusters of orthologous groups，COG) 及其研究意義及其研究意義 直系同源集簇即指由1個共同的祖先基因衍生的1組基因，包括不同基因組中執(zhí)行同一生物學功能的種間同源物(ortholog)，也包括同一基因組中因基因加倍產(chǎn)生的種內(nèi)同源物(paralog)，或平行基因。 直

23、系同源集簇綜合了比較基因組學、種系發(fā)生學和蛋白質(zhì)分類學的信息，對預測新基因的功能具有重要意義。 COLLEGE OF LIFE SCIENCESCluster of orthologous genes (COG)Comparison 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 info

24、rmation of COG relationships and annotations can be stored in databases.Relationship between several yeast and bacterial orthologs in NCBI COG database COLLEGE OF LIFE SCIENCESCOG database can be used to predict gene functions思考題思考題 如何證明某一生物在進化過程中發(fā)生了全基因組的倍增事件而非個別基因的復制? COLLEGE OF LIFE SCIENCESComparative genomics of odorant and pheromone re