Are essential genes conserved? Fatemeh Ashari Ghomi University of Canterbury fatemeh.asharighomi@pg.canterbury.ac.nz October 20, 2016 1/16 Fatemeh Ashari Ghomi Are essential genes conserved?
Essentiality and conservation Are essential genes conserved? Essential genes are the set of genes required for the growth of an organism. Conserved genes have emerged long time ago and are not lost yet. 2/16 Fatemeh Ashari Ghomi Are essential genes conserved?
Transposon insertion 3/16 Fatemeh Ashari Ghomi Are essential genes conserved?
How is transposon insertion related to essentiality? 4/16 Fatemeh Ashari Ghomi Are essential genes conserved?
Bacteria used in this study Klebsiella pneumoniae Ecl8 Klebsiella pneumoniae RH201207 Enterobacter cloacae NCTC 9394 Citrobacter rodentium ICC168 Salmonella Typhimurium SL1344 Salmonella Typhimurium SL3261 Salmonella Typhimurium A130 Salmonella Typhimurium D23580 Salmonella Enteritidis P125109 Salmonella Typhi Ty2 Escherichia coli UPEC ST131 Escherichia coli ETEC CS17 Escherichia coli ETEC H10407 Escherichia coli K-12 MG1655 5/16 Fatemeh Ashari Ghomi Are essential genes conserved?
Are there biases in transposon insertion data? 1. Is there any origin of replication bias? 2. Is there any preferred insertion motif bias? 3. Is there any GC bias? 4. Is there any positional bias within genes? 6/16 Fatemeh Ashari Ghomi Are essential genes conserved?
There is a replication bias Distance bias Origin 5 4 insertion index 3 Terminus Origin 2 1 0 origin terminus Terminus Gene position 7/16 Fatemeh Ashari Ghomi Are essential genes conserved?
There is almost no preferred insertion motif bias C T A C G G G G T C A C A C T 1.0 G G C T G C probability A T G A C G C T T G T A G A T G 0.5 T C G T A T C A T G G A T C T C G A A T A T A C A T C T C A C A G C A C G C C G T A G A A T G 0.0 insertion site -10 +10 2.0 bits 1.0 C G G G A C G T C A C T T A C G C 0.0 T T T A G A A A G T T T C A A G T C A C C G A T C G T A G T C A C A T C G G insertion site -10 +10 8/16 Fatemeh Ashari Ghomi Are essential genes conserved?
There is a GC bias GC bias 5 DNA- Binding 4 Protein insertion index 3 AT AAT GAT T AT T ACT A 2 1 Transposon 0 0.2 0.3 0.4 0.5 0.6 0.7 GC content S. Kimura, T. P. Hubbard, B. M. Davis, and M. K. Waldor. The nucleoid binding protein h-NS biases genome-wide transposon insertion landscapes. 9/16 Fatemeh Ashari Ghomi Are essential genes conserved?
Essential genes have more insertions at the ends while beneficial losses have less insertions at the ends Essential Beneficial loss 0.4 Functional Mean Insertion Index Start Stop Mean Insertion Index 2 part First 5% internal 0.2 Last 20% First 5% internal 1 Last 20% Functional Stop Start Start 0 0 part 5' 3' 5' 3' Position Position 10/16 Fatemeh Ashari Ghomi Are essential genes conserved?
Most of the essential genes are single copy genes and most of the beneficial losses are genus specific All clusters 200 Frequency n = 7280 Essential Ambiguous Single copy Non − essential Multi-copy Beneficial loss Genus specific 0 0 1 2 3 4 Insertion Index Genus specific Single copy Multi − copy 200 n = 3367 n = 2984 n = 929 0 0 1 2 3 4 0 1 2 3 4 0 1 2 3 4 11/16 Fatemeh Ashari Ghomi Are essential genes conserved?
Essential genes are mostly related to replication, transcription, and translation Essential genes ribosomal synthetase polymerase division cell ligase shape−determining riboflavin carboxylase Word topoisomerase dna−directed initiation acyl−carrier−protein translation preprotein cytidylyltransferase carboxyl thymidylate cyclohydrolase methion yl−trna 0 50 100 150 −log10(P−value) 12/16 Fatemeh Ashari Ghomi Are essential genes conserved?
Non-essential genes are mostly membrane associated Non−essential genes transporter permease dehydrogenase flagellar transport oxidoreductase reductase nitrate anaerobic Word abc−type atpase repair periplasmic hydrolase efflux lyase formate hydrogenase glutathione sensor 0 20 40 60 −log10(P−value) 13/16 Fatemeh Ashari Ghomi Are essential genes conserved?
Beneficial losses are mostly putative and hypothetical proteins or related to mobile genetic elements Beneficial losses transposase putative iscro1 pathogenicity island hypothetical fimbrial insertion is200 Word effector prophage secreted virulence invasion membrane insa exported universal insb outer 0 50 100 −log10(P−value) 14/16 Fatemeh Ashari Ghomi Are essential genes conserved?
Summary 1. Biases should be considered before evaluating essentiality. 2. Essential genes are more likely to be conserved. 3. Multi-copy genes are mostly non-essential. 4. Beneficial losses are mostly genus specific. 5. Essential genes are mostly related to replication, transcription, and translation. 6. Non-essential genes are mostly membrane associated. 7. Beneficial losses are mostly putative and hypothetical proteins or related to mobile genetic elements. 15/16 Fatemeh Ashari Ghomi Are essential genes conserved?
Acknowledgement Paul Gardner Anthony Poole Lars Barquist UC bioinformatcs group 16/16 Fatemeh Ashari Ghomi Are essential genes conserved?
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