Ohnologs and Regulatory Networks Robbie Sedgewick Group Meeting March 2, 2006.

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Presentation transcript:

Ohnologs and Regulatory Networks Robbie Sedgewick Group Meeting March 2, 2006

Ohnologs: paralogs that arose through polyploidization ● Ohnologs taken from YGOB (Byrne & Wolfe 2005) ● 554 Ohnolog pairs ● 1108/6540 = 17% of yeast genome is an ohnolog ● Relatively complete dataset. ● Sparse graph

Regulatory Network ● Harbison et al ● Used CHIP to identify binding locations for 203 TFs ● Of those, 102 TF’s had enough hits to determine TF binding sites (motifs) computationally with constraints on binding strength and (optionally) conservation. ● Noisy. ● Not complete.

Basic facts about the regulatory data. p < 0.001P < No conservation “Loose” 9778 regulations Conserved in 2 yeasts Conserved in 3 yeasts “Strict” 3328 regulations

Duplicated transcription factors * Number of Ohnologs expected to be TFs 972*102/6540 =15 Ohnologs obs (exp) Paralogs obs (exp) 102 TFs Count37 (15) * 51 (40) Pairs TFs Count68 (30)110 (80) Pairs In some cases, only one member of a pair is considered a TF in Harbison et al data.

For more ohnolog and paralog stats with correlation coefficients: php/Ohnolog_and_paralog_pairs_that_are_transcri ption_factors

Combining ohnology and regulation g1 is significantly similar to g3 g1 regulates g2 g1 g2 g3 g4g5 g4 is significantly similar to g5 and regulates g5

Compare with randomized graphs Compare with paralogs Null hypotheses

Paralogs ● Use sequence similarity to determine Paralogy. ● Eval cutoff of (soon to use NC) ● 8572 paralogous pairs ● Dense (compared to ohnologs) ● Error prone

Randomization method ● Method due to George and Robbie ● Take two networks and scramble the name mapping between them. ● Results in random combination of graphs that preserves network properties (e.g., node degree) of both component graphs.

Randomization method (name lookup) (scrambled lookup table)

Results How often is a gene regulated by both members of an ohnolog pair? How often are both members of an ohnolog pair regulated by the same TF? Geometric motifs

…both members of an ohnolog pair? …only one member of an ohnolog pair? How many genes are regulated by … For comparison, how many ohnolog pairs regulate at least one common target? Note: a target may be counted more than once if regulated by more than one ohnolog pair.

Genes regulated by only one member of an ohnolog pair Strict Genes regulated by both members of an ohnolog pair Ohnolog pairs that regulate at least one common target TrianglesNumRandavp-val Ohnologs Paralogs NumRandavp-val Ohnologs Paralogs x10 -3 PairsNumRandavp-val Ohnologs Paralogs

Genes regulated by only one member of an ohnolog pair Loose Genes regulated by both members of an ohnolog pair Ohnolog pairs that regulate at least one common target

Results How often is a gene regulated by both members of an ohnolog pair? How often are both members of an ohnolog pair regulated by the same TF? Geometric motifs

…both members of an ohnolog pair? …only one member of an ohnolog pair? How often does a transcription factor regulate For comparison, how many ohnolog pairs have at least one regulator in common?

Strict Genes that regulate only one member of an ohnolog pair TFs that regulate both members of an ohnolog pair Ohnolog pairs have at least one regulator in common TrianglesNumRandavp-val Ohnologs Paralogs NumRandavp-val Ohnologs Paralogs PairsNumRandavp-val Ohnologs Paralogs

Loose Genes that regulate only one member of an ohnolog pair TFs that regulate both members of an ohnolog pair Ohnolog pairs have at least one regulator in common

Results How often is a gene regulated by both members of an ohnolog pair? How often are both members of an ohnolog pair regulated by the same TF? Geometric motifs

Motifs and evolution We can understand complex motifs by considering what happens after a whole genome duplication. WGD Loss

Results: one pair Regulates Partner Regulate each other Strict NumRandavp-val Ohnologs40.526x10 -4 Paralogs81.02x10 -4 NumRandavp-val Ohnologs10.04 Paralogs

Results: one pair Regulates Partner Regulate each other Loose NumRandavp-val Ohnologs x10 -3 Paralogs112.61x10 -4 NumRandavp-val Ohnologs Paralogs

For pictures of these motifs ● reg.pdf reg.pdf ● reg-loose.pdf reg-loose.pdf

Motifs and evolution We can understand complex motifs by considering what happens after a whole genome duplication. WGD Loss

Results: Two pairs 0 loss 1 loss 2 loss Strict

Results: Two pairs 0 loss 1 loss 2 loss Loose

For a table with more complete motif stats:

An example: Duplicated Iron Pathway? ● AFT1 and AFT2 are TFs that are also ohnologs and both regulate iron deprivation response pathways. ● 26 of the 60 genes regulated by AFT2 are ohnologs (strict). ● Maybe iron deprivation response pathway was duplicated in WGD? buffering? AFT1 and AFT2 motif: d_friends2.pdf

Additional Sources of Data ● Gene Coexpression ● Synthetic Lethal interactions ● Protein-Protein interactions (Y2H) ● Domain information ● Genes that were ohnologs (singletons from YGOB)