比較基因組學課件

比較基因組學Comparative

Genomics1Some

well-known

modelorganisms

Escherichia

coli

—

model

prokaryote

Saccharomyces

cerevisiae

(baker’s

yeast)

—

model

unicellulareukaryote

Caenorhabditis

elegans

(nematode)

—

an

excellent

model

formulticellular

developmental

biology

Drosophila

melanogaster

(fruit

fly)

—

model

insect

Danio

rerio

(zebrafish)

—

a

good

model

for

vertebratedevelopmental

biology

Mus

musculus

(mouse)

—

model

mammal,

important

for

the

studyof

human

genome

Arabidopsis

thaliana

(thale

cress

)

—

model

dicot

plant

Oryza

sativa

(rice)

—

model

cereal

and

monocot

plantCOLLEGE2OFLIFESCIENCESWhat

the

genomes

of

modelorganisms

tell

usAlmost

every

human

gene

has

a

counterpartinthe

mouse

and

some

blocks

of

DNA

are

provingimpossible

to

tell

apart3Human

genes

mapped

ontomouse

chromosomes4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COLLEGE5OFLIFESCIENCES1、比較基因組學定義及其研究意義：定義: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)與功能方面的親源關(guān)系及其內(nèi)在聯(lián)系的一門新興學科。研究意義

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。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。COLLEGE6OFLIFESCIENCESSimilarity

vs.

Homology(相似性與同源性)7

Similarity:

a

phenomenon

that

differentgenes

or

genome

segments

show

similarsequences.

Homology:

a

phenomenon

that

differentgenes

or

genome

segments

have

thesameancestor.相似性與同源性相似性(similarity)：是指一種很直接的數(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(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。COLLEGE8OFLIFESCIENCEOrtholog

vs.

Paralog9

Ortholog（直向同源物）:homologous

genesor

DNA

sequences

in

different

genomes(species)

Paralog（橫向同源物）:homologous

genesor

DNA

sequences

in

the

same

genome(species)paralogsorthologsCOLLEGE10OFLIFESCIENCESColinearity

vs.

Synteny199911

Colinearity:

conservation

ofgene

content

and

order

indifferent

genomes,

which

is

areflection

of

homology

Synteny:

conserved

linkageamong

genes

in

differentgenomes

regardless

of

order

macrosynteny

vs.

microsyntenyMurphy

et

al.

Genome

Research1999共線性與同線性共線性（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，它反應了一種同源關(guān)系。

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12宏觀共線性和微觀共線性

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。

微觀共線性(microsynteny)：

是指物理圖上基因順序的一致排列。COLLEGE13OFLIFESCIENCEApproaches

for

genome

comparison14

Genome

comparison

is

to

identify

the

homologoussequences

among

different

genomes.

Two

methodscan

be

used

for

this

purpose:Hybridization-based

comparison:

using

Southernhybridization

to

identify

homologous

sequences.Sequence-based

comparison:

using

computerto

identifyhomologous

sequences.Hybridization-based

comparison

Use

the

same

set

of

DNA

probes

to

locateorthologs

on

genetic

or

physical

maps

of

differentspecies

with

the

method

of

Southern

blot,

andthen

compare

the

order

of

orthologs

inthosespecies.

The

comparison

will

show

the

macro-colinearityamong

the

species

being

tested.COLLEGE15OFLIFESCIENCESPatterns

of

genome

colinearityThe

use

of

the

same

set

ofmolecular

markers

(A–P)

forgenetic

mapping

experiments

indifferent

species

allows

thealignment

of

the

resultingchromosome

maps.

In

the

leftfigure,

two

chromosome

maps(I

and

1)

are

shown,

which

arecompletely

colinear.COLLEGEOFLIFESCIENCES16Comparative

maps

of

the

wheat

genome

describedinterms

of

the

rice

genome

(A)

and

theAe.umbellulatagenome

(B)17Comparativegenetic

mapsof

fivegrassspecies:

rice,foxtail

millet,sorghum,maize

andbarleyFive grass

genomes,

one

consensus

map.18Sequence-based

comparison

Comparison

of

overall

statistics

ofnucleotide

sequence

Comparison

of

coding

sequence

(genes)

Comparison

of

segmental

sequence

or

whole

genome

(genome

alignment)COLLEGE19OFLIFESCIENCESComparison

of

overall

nucleotide

statistics

Comparisonofoverallnucleotidestatisticspresent

aglobalviewofthesimilaritiesanddifferencesofthegenomes,including:genome

sizeoverall

(G+C)

contentregions

of

different

(G+C)

contentgenome

signature

codon

usage

biases

amino

acid

usage

biases

the

ratio

of

observed

dinucleotide

frequency

and

the

expectedfrequency

given

random

nucleotide

distributionCOLLEGEOFLIFESCIENCE20Comparison

of

genes

Genenumber

Genehomology

Genecategory

Genestructure

Gene

functional

relationship

and

interactionCOLLEGE21OFLIFESCIENCEGene

comparison

provides

a

possible

waytopredict

gene

association

and

proteininteraction

Gene

association:

Genes

involved

in

the

same

metabolicpathwaytend

to

appear

together

in

a

genome.

Hence,

by

examining

whethertwo

genes

are

correlated

in

many

genomes,

it

could

be

deducedthat

the

two

genes

might

be

functionally

associated.

Protein

interaction:

If

two

genes

(say

A

and

B)

in

several

genomesare

found

to

have

been

fused

in

some

other

genomes,

it

could

bededuced

that

the

proteins

coded

by

genes

A

and

B

might

interacteither

functionally

Sequence-based

comparison

or

physically.22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4—5

kb，并保持很好的共線性。COLLEGE23OFLIFE

SCIENCEGenome

alignmentLong

sequence

alignment

is

problematic

due

to

rearrangement.

Presently,almost

all

of

the

alignment

algorithms

first

identify

large

conservedsequence

elements

between

the

two

genome

sequences,

and

then

generatethe

overall

alignment.

In

general,

similar

genomes

may

result

in

betteralignment.COLLEGE24OFLIFESCIENCEAlignment

between

the

4th

chromosomes

ofindica

rice

GLA4

and

japonica

rice

NipponbareThe

above

figure

shows

good

global

colinearity

on

chromosome

4between

the

two

subspecies

of

rice

except

for

some

indels.25Alignment

between

rice

chromosome

4

andfive

A.

thaliana

chromosomesThe

above

figure

shows

that

all

the

five

Arabidopsis

chromosomeshave

orthologs

on

rice

chromosome4.26Within

genome

comparison

can

revealparalogous

(duplicated)

regionsThe

left

figureshows

that

most

ofthe

Arabidopsisgenome

sequence

isduplicated.

Blockswith

the

samecolours

representparalogous

regions.27Large-scale

duplications

in

plant

genomesThe

gene

arrangement

of

a

region

mapping

to

A.

thaliana

chromosome

1is

compared

to

its

counterpart

on

chromosome

3.

Genes

in

common

toboth

regions

are

shown

as

white

boxes.

Lines

connect

homologoussequences.

Black

boxes

represent

genes

unique

to

the

chromosome

1

orchromosome

3

region,

respectively.

The

location

of

a

box

relativetothe

sequence

drawn

as

a

line

indicates

the

direction

of

transcription(Rossberg

et

al.,

2001).COLLEGE28OFLIFESCIENCES直系同源集簇(clusters

of

orthologousgroups，COG)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。COLLEGE29OFLIFESCIENCESCluster

of

orthologous

genes

(COG)

Comparison

of

genesfromdifferent

genomes

couldidentify

orthologous

genesand

establish

the

clustersof

orthologous

genes(COGs),

which

usuallyrepresent

classes

ofmetabolic

function.

The

information

of

COGrelationships

andannotations

can

be

storedindatabases.Relationship

betweenseveral

yeast

andbacterial

orthologs

inNCBI

COG

databaseCOLLEGEOFLIFESCIENCES30COG

database

can

be

used

to

predictgenefunctions31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?COLLEGE32OFLIFESCIENCESThank

you

!33Questions?Comparative

genomics

of

odorant

and