Nothing in (computational) biology makessense except in the light of evolution

after Theodosius Dobzhansky (1970)

Comparative genomics and the new perspective on genome evolution

Conservation of gene order in bacterial species of the same

genus1

101

201

301

401

501

601

1 101 201 301 401

M. genitaliumvs

M. pneumoniae

Conservation of gene order in closely related bacterial genera

C. trachomatisvs

C. pneumoniae

1

101

201

301

401

501

601

701

801

901

1001

1 101 201 301 401 501 601 701 801

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

Proteobacterial subdivision

P. aeruginosavs

E. coli

1101201301401501601701801901

1001110112011301140115011601170118011901200121012201230124012501260127012801290130013101320133013401350136013701380139014001410142014301440145014601470148014901500151015201530154015501

1 101

201

301

401

501

601

701

801

901

1001

1101

1201

1301

1401

1501

1601

1701

1801

1901

2001

2101

2201

2301

2401

2501

2601

2701

2801

2901

3001

3101

3201

3301

3401

3501

3601

3701

3801

3901

4001

4101

4201

ecoli

paer

<0.3

0.3-0.8

0.8-1.3

>1.3

Genome Alignments - MethodProtein sets from completely genomes

BLAST cross-comparison

Pairwise Genome AlignmentLocal alignment algorithmLamarck (gap opening penalty,gap extension penalty); statisticswith Monte Carlo simulations

Table of Hits

Template-Anchored Genome Alignment

Genome Alignments - Statistics

0.0

0.1

0.2

0.3

0.4

0.52 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

>20

cpneu-ctra

mjan-mthe

bsub-ecoli

drad-aero

Distribution of conserved gene string lengths

Genome Alignments - StatisticsPairwise No. No. % in % inalignments: strings genes Gen1 Gen2

all homologsecoli-hinf 138 566 13% 33%ecoli-bsub 89 322 8% 8%ecoli-mjan 10 30 1% 2%

probable orthologsecoli-hinf 105 482 11% 28%ecoli-bsub 34 168 4% 4%ecoli-mjan 12 33 1% 2%

Genome Alignments - Statistics

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

aero af

ul

mjan

mth

epy

ro

aqua

ebb

urbs

ub cac

cjej

cpne

uct

radr

adec

oli hinf

hpyl

mge

n

mpn

eum

tub

nmen

rpxx

syne

cho

tmar tp

aluu

re

Not in gene strings

In non-conserved gene strings (directons)

In conserved gene strings

Breakdown of genesin the genome

Genome Alignments - StatisticsFraction of the genome in conserved gene strings - from

template-anchored alignments

Minimum Synechocystis sp. 5%

Aquifex aeolicus 10%Archaeoglobus fulgidus 13%Escherichia coli 14%Treponema pallidum 17%

Maximum Thermotoga maritima 23%Mycoplasma genitalium 24%

-proteobacteria-proteobacteria

Bacillus/Clostridium groupmycoplasmas

spirocheteschlamydias

AaeTma

cyanobacteria

actinobacteriaDra

Hbs

TxxAfu

PxxMjaMth

crenarchaea

-proteobacteria

eukaryota

Archaea

Bacteria

The three domains of life: the Tree

Eukaryotes

Archaea

Bacteria 729188

21087

111

245

315

496

The three domains of life: relationships within clusters of orthologs(COGs)

A+B+E

A+E

A+B

A

All COGs Pan-archaeal COGs

0

10

20

30

40

50

60

70

information metabolic cellular unknow n

A+E-B

A+E-B A+E-B

A+E-BA+B-E

A+B-E

A+B-E

A+B-E

Protein functions in the archaeo-eukaryotic and archaeo-bacterial subsets of the conserved archaeal core (310 COGs total)

Eco E

Sce E cytAth E cyt

Hsa Q

Sce Q

Eco QHin Q

Mth EMja E

Pho E

Afu E

Sso E

Hpy E /1/

Hpy E /2/

Hin E

Tpa EBbu ECel E mit

Sce E mitCtr EMtu E

Ssp EMpn E

Mge EBsu EAae E

Mge WMpn W

Sce W mitCel W mit

Ssp WHpy W

Bsu WMtu W

Hin W Eco W

Aae WCtr W Tpa W

Bbu W

Afu WMth WMja W

Pho W

Sce W cytHsa W cyt

Phylogenetic trees of aminoacyl-tRNA synthetases: HGT comes out loud and clear

Csp3_Hsa

PC_Ddis

ActD_MxanXF2779_Xfa

Mlr3300_MloYOR197w_Sce

MC_SpoMC5_At

MC4_AtMC2_At

MC_HbrMC3_At

MC1_At

MC_Rsph MC_Geos

PK3_Scoe

Gingipain K_Pgin

Gingipain R_Pgin

CASP-like_Deha

Mlr3303_Mlo

Mlr2366_MloMll2372_Mlo

Mlr3463_MloMlr1804_Mlo

Mll5190_Mlo

PC_Hsa

PC_CelCsp1_Hsa

Csp2_HsaCED3_Cel

Csp10_Hsa

Csp9_Hsa

Phylogenetic tree of the caspase-like protease superfamily

Eukaryotic programmed cell death - the bacterial contribution

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

HGTLoss

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

2 parsimoniousscenarios

0

100

200

300

400

500

600

700

0 2 4 6 8 10 12

Number of events (I)

Nu

mb

er

of

CO

Gs

Number of gene loss and HGT events in most parsimonious evolutionary scenarios for COGs (I values).

Conclusion

Comparative genomics shows that genome evolutionis a highly dynamic process dominated by gene shuffling,lineage-specific gene loss and horizontal gene transfer