比較基因組學(xué)(1)

1、編輯編輯pptppt1 1 編輯編輯pptppt2 2 Escherichia coli model prokaryote Saccharomyces cerevisiae (bakers yeast) model unicellular eukaryote Caenorhabditis elegans (nematode) an excellent model for multicellular developmental biology Drosophila melanogaster (fruit fly) model insect Danio rerio (zebrafish) a go

2、od model for vertebrate developmental biology Mus musculus (mouse) model mammal, important for the study of human genome Arabidopsis thaliana (thale cress ) model dicot plant Oryza sativa (rice) model cereal and monocot plant COLLEGE OF LIFE SCIENCES 編輯編輯pptppt3 3 Almost every human gene has a count

3、erpart in the mouse and some blocks of DNA are proving impossible to tell apart 編輯編輯pptppt4 4 編輯編輯pptppt5 5 1、比較基因組學(xué)的定義和研究意義 2、比較基因組學(xué)常用的基本概念 3、比較基因組學(xué)研究的方法和相關(guān)研究 4、相關(guān)研究論文簡(jiǎn)介 COLLEGE OF LIFE SCIENCES 編輯編輯pptppt6 6 1、比較基因組學(xué)定義及其研究意義：、比較基因組學(xué)定義及其研究意義： 定義定義:比較基因組學(xué)是在基因組學(xué)水平上研究不同比較基因組學(xué)是在基因組學(xué)水平上研究不同 物種和品系之間在基因組結(jié)

4、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(xué)科。關(guān)系及其內(nèi)在聯(lián)系的一門新興學(xué)科。 研究意義研究意義 (1) 指導(dǎo)在遺傳與基因組信息較為缺乏的物種中 進(jìn)行基因的克隆和功能研究。 (2) 通過(guò)研究生物進(jìn)化過(guò)程中，基因組所發(fā)生的 倍增、缺失、重組，對(duì)于生物進(jìn)化研究，具 有重大意義。 COLLEGE OF LIFE SCIENCES 編輯編輯pptppt7 7 Similarity:Similarity: a phenomenon that different genes or genome segments show similar sequences.

5、 Homology:Homology: a phenomenon that different genes or genome segments have the same ancestor. 編輯編輯pptppt8 8 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(gè)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 LIFE SCIENCE 編輯編輯pptppt9 9 Ortholog（直向同源物）（直向同源物）: ho

6、mologous 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) 編輯編輯pptppt1010 paralogs orthologs COLLEGE OF LIFE SCIENCES 編輯編輯pptppt1111 Colinearity: conservation of gene content and order in different genomes, whi

7、ch is a reflection of homology Synteny: conserved linkage among genes in different genomes regardless of order macrosynteny vs. microsyntenymacrosynteny vs. microsynteny 1 9 9 9 Murphy et al. Genome Research 1999 編輯編輯pptppt1212 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。 同線性（同線性（

8、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 編輯編輯pptppt1313 宏觀共線性（宏觀共線性（macrosyntenymacrosynteny） ： 指遺傳連鎖圖上錨定標(biāo)記排列次序的一致性。指遺傳連鎖圖上錨定標(biāo)記排列次序的一致性。 微觀共線性微觀共線性(microsynteny) (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 SCIENCE 編輯編輯pptppt1414 Genome comparison is to identif

9、y 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. 編輯編輯pptppt1515 Use the same set of

10、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 SCIENCES 編輯編輯pptppt1616 The use o

11、f 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 SCIENCES 編輯編輯pptppt1717 編輯編輯pptppt1818 Five

12、 grass genomes, one consensus map. 編輯編輯pptppt1919 Comparison of overall statistics of nucleotide sequence Comparison of coding sequence (genes) Comparison of segmental sequence or whole genome (genome alignment) COLLEGE OF LIFE SCIENCES 編輯編輯pptppt2020 Comparison of overall nucleotide statistics pres

13、ent a global 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 nucle

14、otide distribution COLLEGE OF LIFE SCIENCE 編輯編輯pptppt2121 Gene number Gene homology Gene category Gene structure Gene functional relationship and interaction COLLEGE OF LIFE SCIENCE 編輯編輯pptppt2222 Gene association: Genes involved in the same metabolic pathway tend to appear together in a genome. Hen

15、ce, 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 deduced that the proteins cod

16、ed by genes A and B might interact either functionally Sequence-based comparison or physically. 編輯編輯pptppt2323 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 SCIENCE 編輯編輯pptppt2424 Long sequence alignment is problematic due to rearrangement. Presently,

17、 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 SCIENCE 編輯編輯pptppt2525 The above figure shows good global co

18、linearity on chromosome 4 between the two subspecies of rice except for some indels. 編輯編輯pptppt2626 The above figure shows that all the five Arabidopsis chromosomes have orthologs on rice chromosome 4. 編輯編輯pptppt2727 The left figure shows that most of the Arabidopsis genome sequence is duplicated. B

19、locks with the same colours represent paralogous regions. 編輯編輯pptppt2828 The gene arrangement 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 repr

20、esent 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). COLLEGE OF LIFE SCIENCES 編輯編輯pptppt2929 直系同源集簇直系同源集簇(clusters of orthologous groups，COG) 及其研究意

21、義及其研究意義 直系同源集簇即指由1個(gè)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(xué)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。 直系同源集簇綜合了比較基因組學(xué)、種系發(fā)生 學(xué)和蛋白質(zhì)分類學(xué)的信息，對(duì)預(yù)測(cè)新基因的功能具 有重要意義。 COLLEGE OF LIFE SCIENCES 編輯編輯pptppt3030 Comparison of genes from different genomes could identify orthologous genes and establish the clust

22、ers 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 bacterial orthologs in NCBI COG database COLLEGE OF LIFE SCIENCES 編輯編輯pptppt3131 編輯編輯pptppt3232 如何證明某一生物在進(jìn)化過(guò)程中發(fā)生 了全基因組的倍增事件而非個(gè)別基因 的復(fù)制? COLLEGE OF LIFE SCIENCES 編輯編輯pptppt3333 編輯編輯pptppt3434 Comparative genomics of odorant and pheromone receptor genes in rodents 嚙齒動(dòng)物