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Nothing in (computational) biology makes

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Presentation on theme: "Nothing in (computational) biology makes"— Presentation transcript:

1 Nothing in (computational) biology makes
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)

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3 Conservation of gene order in bacterial species of the same genus
1 101 201 301 401 501 601 M. genitalium vs M. pneumoniae

4 Conservation of gene order in closely related bacterial genera
1 101 201 301 401 501 601 701 801 901 1001 C. trachomatis vs C. pneumoniae

5 Lack of gene order conservation - even in “closely related” bacteria of the same Proteobacterial subdivision P. aeruginosa vs E. coli

6 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

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8 Genome Alignments - Statistics
0.0 0.1 0.2 0.3 0.4 0.5 2 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

9 Genome Alignments - Statistics
Pairwise No. No. % in % in alignments: strings genes Gen1 Gen2 all homologs ecoli-hinf % 33% ecoli-bsub % 8% ecoli-mjan % 2% probable orthologs ecoli-hinf % 28% ecoli-bsub % 4% ecoli-mjan % 2%

10 Genome Alignments - Statistics
500 1000 1500 2000 2500 3000 3500 4000 4500 5000 aero aful mjan mthe pyro aquae bbur bsub cac cjej cpneu ctra drad ecoli hinf hpyl mgen mpneu mtub nmen rpxx synecho tmar tpal uure Not in gene strings In non-conserved gene strings (directons) In conserved gene strings Breakdown of genes in the genome

11 Genome Alignments - Statistics
Fraction 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%

12 The three domains of life: the Tree
-proteobacteria -proteobacteria -proteobacteria spirochetes Bacteria chlamydias Bacillus/Clostridium group mycoplasmas actinobacteria Dra cyanobacteria Aae Tma Mth Mja Pxx Archaea Txx Afu crenarchaea Hbs eukaryota

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19 The three domains of life: relationships within clusters of orthologs
(COGs) Eukaryotes A 245 496 Bacteria A+B 1882 729 111 A+B+E 1087 Archaea A+E 315 Pan-archaeal COGs All COGs

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

21 Phylogenetic trees of aminoacyl-tRNA synthetases:
HGT comes out loud and clear Eco E Sce E cyt Ath E cyt Hsa Q Sce Q Eco Q Hin Q Mth E Mja E Pho E Afu E Sso E Hpy E /1/ Hpy E /2/ Hin E Tpa E Bbu E Cel E mit Sce E mit Ctr E Mtu E Ssp E Mpn E Mge E Bsu E Aae E Mge W Mpn W Sce W mit Cel W mit Ssp W Hpy W Bsu W Mtu W Hin W Eco W Aae W Ctr W Tpa W Bbu W Afu W Mth W Mja W Pho W Sce W cyt Hsa W cyt

22 Eukaryotic programmed cell death - the bacterial contribution
PC_Hsa Csp1_Hsa Mlr1804_Mlo PC_Cel Csp2_Hsa CED3_Cel Mlr3463_Mlo Mll5190_Mlo Csp10_Hsa Mll2372_Mlo Mlr2366_Mlo Csp3_Hsa Mlr3303_Mlo Csp9_Hsa CASP-like_Deha Gingipain R_Pgin PC_Ddis ActD_Mxan XF2779_Xfa Gingipain K_Pgin Mlr3300_Mlo YOR197w_Sce PK3_Scoe MC1_At MC_Spo MC_Geos MC3_At MC5_At MC_Rsph MC_Hbr MC4_At MC2_At Phylogenetic tree of the caspase-like protease superfamily

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24 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 IQ=1 IQ=1 IQ=2 IQ=2 A B C D 2 parsimonious scenarios Loss HGT

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

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


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