Title: Evolutionary Mechanisms For Growth Of
1Evolutionary Mechanisms For Growth Of Gene
Regulatory Networks
M. Madan Babu
MRC Laboratory of Molecular Biology, Cambridge
2(No Transcript)
3Outline
4Organisation of the gene regulatory network
5Network Growth
What are the mechanisms of these events?
6Mechanisms for the creation of new genes
OR Recombination/Innovation
7Dataset used in the analysis
8Determining Homology
9Duplication events in the real network
1/2 of the TFs and TGs have evolved by
duplication
3/4 of the TFs and 1/2 of TGs have evolved by
duplication
10Duplication of the basic unit
11Network growth by duplication
Duplication of the basic unit
12Network growth by duplication
Duplication of the basic unit
Innovation of of regulatory interaction
13Consequence of duplicating a target gene
14Consequence of duplicating a transcription factor
15Consequences of duplicating a TF and TG
Madan Babu, M. Teichmann, S.A., NAR (2003)
16Contribution of duplication to network growth
17Duplication of transcription factors or target
genes or both, followed by conservation of
regulatory interactions have contributed between
1/3 and 1/2 of the regulatory networks in E. coli
and Yeast
18Network growth by duplication
Duplication of the basic unit
Inheritance / Conservation of regulatory
interaction
19Duplication followed by innovation of new
interaction
202/5 and 1/2 of the regulatory network in both
organisms has evolved by duplication of genes,
followed by loss of old interactions and gain of
new interactions
21Network growth by Innovation
221/10 of the regulatory network in both organisms
has evolved by innovation
23Contribution of the different mechanisms for the
growth of the regulatory network
24Conclusions
Duplication of transcription factors or target
genes or both, followed by conservation of
regulatory interactions have contributed between
1/3 and 1/2 of the regulatory networks in E. coli
and Yeast
2/5 and 1/2 of the regulatory network in both
organisms has evolved by duplication of genes,
followed by loss of old interactions and gain of
new interactions
1/10 of the regulatory network in both organisms
has evolved by innovation
25Acknowledgements
Sarah Teichmann
MRC - Laboratory of Molecular Biology Cambridge
Commonwealth Trust Overseas Research
Studentship Trinity College, Cambridge
YBF organisers and members in the audience
26Statistical significance
27Duplication events in the E. coli network
111 Transcription factors with domain assignment
570 Target genes with domain assignment
82 Transcription factors with homologues
401 Target genes with homologues
18 homologous groups
90 homologous groups
1/2 of the TFs and TGs have evolved by duplication
28Duplication events in the yeast network
312 Target genes with domain assignment
80 Transcription factors with domain assignment
193 Target genes with homologues
70 Transcription factors with homologues
52 homologous groups
14 homologous groups
3/4 of TFs 1/2 of TGs have evolved by
duplication
29Network motifs Patterns of inter-connections
that recur in many different parts of the network
30
29
42
131
Shenn-orr et. al., Nat. Gen 2002 Lee, C.,
Science 2003
30Evolution of network motifs
Duplication of TF TG
Duplication of TF
Duplication of TG
Growth models
Motifs
Single Input Module
Feed-Forward Motif
Dense Overlapping Regulons