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Comparative genomics and the new perspective on genome evolution. Nothing in ( computational ) biology makes sense except in the light of evolution. after Theodosius Dobzhansky (1970). 1. 101. 201. 301. 401. 1. 101. 201. 301. 401. 501. 601.

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slide1

Comparative genomics and the new perspective on genome evolution

Nothing in (computational) biology makes

sense except in the light of evolution

after Theodosius Dobzhansky (1970)

conservation of gene order in bacterial species of the same genus

1

101

201

301

401

1

101

201

301

401

501

601

Conservation of gene order in bacterial species of the same genus

M. genitalium

vs

M. pneumoniae

conservation of gene order in closely related bacterial genera

1

101

201

301

401

501

601

701

801

1

101

201

301

401

501

601

701

801

901

1001

Conservation of gene order in closely related bacterial genera

C. trachomatis

vs

C. pneumoniae

slide5
Lack of gene order conservation - even in “closely related” bacteria of the same Proteobacterial subdivision

P. aeruginosa

vs

E. coli

genome alignments method
Genome Alignments - Method

Protein sets from completely genomes

BLAST cross-comparison

Table of Hits

Pairwise Genome Alignment

Local alignment algorithm

Lamarck (gap opening penalty,

gap extension penalty); statistics

with Monte Carlo simulations

Template-Anchored Genome Alignment

genome alignments statistics

0.5

cpneu-ctra

mjan-mthe

0.4

bsub-ecoli

drad-aero

0.3

0.2

0.1

0.0

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

>20

Genome Alignments - Statistics

Distribution of conserved gene string lengths

genome alignments statistics9
Genome Alignments - Statistics

Pairwise No. No. % in % in

alignments: strings genes Gen1 Gen2

all homologs

ecoli-hinf138 566 13% 33%

ecoli-bsub 89 322 8% 8%

ecoli-mjan 10 30 1% 2%

probable orthologs

ecoli-hinf105 482 11% 28%

ecoli-bsub 34 168 4% 4%

ecoli-mjan 12 33 1% 2%

genome alignments statistics10

5000

4500

4000

3500

3000

2500

2000

1500

1000

500

0

cjej

aful

cac

hinf

tpal

ctra

hpyl

pyro

rpxx

aero

bbur

drad

uure

tmar

ecoli

bsub

mjan

mthe

mtub

mgen

nmen

aquae

cpneu

mpneu

synecho

Not in gene strings

In non-conserved gene strings (directons)

In conserved gene strings

Genome Alignments - Statistics

Breakdown of genes

in the genome

genome alignments statistics11
Genome Alignments - Statistics

Fraction of the genome in conserved gene strings - from

template-anchored alignments

MinimumSynechocystis sp. 5%

Aquifex aeolicus10%

Archaeoglobus fulgidus13%

Escherichia coli14%

Treponema pallidum17%

MaximumThermotoga maritima 23%

Mycoplasma genitalium 24%

slide12

The three domains of life: the Tree

-proteobacteria

-proteobacteria

-proteobacteria

spirochetes

chlamydias

Bacteria

Bacillus/Clostridium group

mycoplasmas

actinobacteria

Dra

cyanobacteria

Aae

Tma

Mth

Mja

Pxx

Archaea

Txx

Afu

crenarchaea

Hbs

eukaryota

slide19

The three domains of life: relationships within clusters of orthologs

(COGs)

Eukaryotes

A

245

496

Bacteria

A+B

1882

729

A+B+E

111

1087

A+E

Archaea

315

Pan-archaeal COGs

All COGs

slide20

Protein functions in the archaeo-eukaryotic and

archaeo-bacterial subsets of the conserved archaeal core

(310 COGs total)

slide21

Tpa W

Ctr W

Bbu W

Aae W

Afu W

Mth W

Mja W

Eco W

Hin W

Mtu W

Pho W

Bsu W

Hpy W

Sce W cyt

Ssp W

Hsa W cyt

Mpn W

Cel W mit

Mge W

Sce W mit

Sce E cyt

Ath E cyt

Hpy E /2/

Eco Q

Hin Q

Hpy E /1/

Hsa Q

Bsu E

Aae E

Mge E

Mpn E

Sce Q

Ssp E

Afu E

Mtu E

Pho E

Hin E

Ctr E

Eco E

Mth E

Sce E mit

Sso E

Tpa E

Mja E

Bbu E

Cel E mit

Phylogenetic trees of aminoacyl-tRNA synthetases:

HGT comes out loud and clear

slide22

Eukaryotic programmed cell death - the bacterial contribution

PC_Hsa

Csp1_Hsa

Mlr1804_Mlo

CED3_Cel

PC_Cel

Csp2_Hsa

Mll5190_Mlo

Mlr3463_Mlo

Csp10_Hsa

Mll2372_Mlo

Mlr2366_Mlo

Csp3_Hsa

Mlr3303_Mlo

Csp9_Hsa

CASP-like_Deha

PC_Ddis

Gingipain R_Pgin

ActD_Mxan

XF2779_Xfa

Mlr3300_Mlo

Gingipain K_Pgin

YOR197w_Sce

MC1_At

PK3_Scoe

MC_Spo

MC3_At

MC5_At

MC_Geos

MC_Rsph

MC_Hbr

MC4_At

MC2_At

Phylogenetic tree of the caspase-like protease superfamily

slide24

Inconsistency Quotient

IQ = minimal number of events (Loss, Emergence, or HGT)

required to reconcile a COG’s phyletic pattern with

the topology of the species tree

A B C D

A B C D

A B C D

A B C D

A B C D

IQ=1

IQ=1

IQ=2

IQ=2

2 parsimonious

scenarios

Loss

HGT

slide25

Number of gene loss and HGT events in most parsimonious

evolutionary scenarios for COGs (I values).

slide26

Conclusion

Comparative genomics shows that genome evolution

is a highly dynamic process dominated by gene shuffling,

lineage-specific gene loss and horizontal gene transfer