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Phase Bias in genes Overlappin Niv Sabath University of Houston Introduction • Overlapping genes are ubiquitous, particularly in bacteria and viruses • Genes can overlap On the same strand (→ →) On opposite strands (→ ← or ← →) • In bacteria ~30% of the genes overlap ~70% of the overlaps are on the same strand Long Overlaps Short Overlaps Same-Strand Overlaps Count Phase 2 Phase 1 Phase 0 5’ 3’ Overlap Length T G A T A A T A G Long Overlaps Short Overlaps Same-Strand Overlaps Count Phase 2 Phase 1 Phase 0 5’ 3’ Overlap Length T G A T A A T A G Long Overlaps Short Overlaps Same-Strand Overlaps Count Phase 2 Phase 1 Phase 0 5’ 3’ Overlap Length 1 T G A T A A T A G Long Overlaps Short Overlaps Same-Strand Overlaps Count Phase 2 Phase 1 Phase 0 5’ 3’ Overlap Length 2 T G A T A A T A G Long Overlaps Short Overlaps Same-Strand Overlaps Count Phase 2 Phase 1 Phase 0 5’ 3’ Overlap Length 4 T G A T A A T A G Long Overlaps Short Overlaps Same-Strand Overlaps Count Phase 2 Phase 1 Phase 0 5’ 3’ Overlap Length 5 T G A T A A T A G Long Overlaps Short Overlaps Same-Strand Overlaps Count Phase 2 Phase 1 Phase 0 5’ 3’ Overlap Length 7 T G A T A A T A G Long Overlaps Short Overlaps Same-Strand Overlaps Count Phase 2 Phase 1 Phase 0 5’ 3’ Overlap Length 8 T G A T A A T A G Long Overlaps Short Overlaps Same-Strand Overlaps Count Phase 2 Phase 1 Phase 0 5’ 3’ Overlap Length 10 T G A T A A T A G Long Overlaps Short Overlaps Same-Strand Overlaps Count Phase 2 Phase 1 Phase 0 5’ 3’ Overlap Length 11 T G A T A A T A G Long Overlaps Short Overlaps “…the phase bias must be a property of gene locations.” “We propose that through some mechanism yet to be determined, the creation of unidirectional gene overlaps of phase +1 confers some advantage.” Count (Cock and Whitworth 2007) Phase 2 Phase 1 Phase 0 5’ 3’ Overlap Length T A G C A T G T A T C A T G G 170 bacterial genomes 15298 long overlaps in phase 1 4153 long overlaps in phase 2 T A G C A T G T A T C A T G G 170 bacterial genomes 15298 long overlaps in phase 1 4153 long overlaps in phase 2 Composition? T A G C A T G T A T C A T G G Scenarios of overlap creation 5’ 3’ 5’ 3’ 5’ 3’ T A G C A T G T A T C A T G G Hypothesis The phase bias in overlap frequency is a result of difference between the frequencies of initiation/termination codons in phase 1 and phase 2 reading frames T A G C A T G T A T C A T G G We examined the frequencies of ATG, the most common start codon, and stop codons in phase 1 and phase 2 reading frames T A G C A T G T A T C A T G G T A G C A T G T A T C A T G G What causes the difference in ATG frequencies? Met Phase 2 Phase 1 Phase 0 Met 5’ T A G C A T G T A T C A T G G 3’ T A T Tyr T G T Cys C A T His T G C Cys A A T Asn T G A Stop G A T Asp T G G T A G C A T G T A T C A T G G Trp What causes the difference in ATG frequencies? Relative abundance of amino acids Phe Val Ala Arg Phase 1 Leu Ser Gln Gly Ile Pro Lys Met Thr Glu Phase 2 T A T Tyr T G T Cys C A T His T G C Cys A A T Asn T G A Stop G A T Asp T G G T A G C A T G T A T C A T G G Trp The frequencies of ATG are correlated with the expected frequencies f 0 NAT f f 0 NNA f 0 GNN 0 TGN r2 = 0.93 r2 = 0.80 T A G C A T G T A T C A T G G Amino-acid frequency ATG frequency Phase bias T A G C A T G T A T C A T G G Acknowledgments Dr. Dan Graur Dr. Giddy Landan NSF © Marko Posavec Why was the correlation between overlap frequency and GC content unnoticed? Long + short overlaps: Phase 1 + phase 2 Phase 1 Phase 2 (64% ATGA) Why was the correlation between overlap frequency and GC content unnoticed? Long + short overlaps: Stop codon usage: Phase 1 + phase 2 TGA Phase 1 Phase 2 (64% ATGA) TAA TAG What is the proportion (P) of overlaps, which are created by each scenario after accounting for ATG frequencies? Rgenes phase1 overlap frequency phase 2 overlap frequency RATG phase1 ATG frequency phase2 ATG frequency Rstop phase1 stop codon frequency phase2 stop codon frequency Rgenes phase1 overlap frequency phase 2 overlap frequency RATG phase1 ATG frequency phase2 ATG frequency Rstop phase1 stop codon frequency phase2 stop codon frequency Rgenes PRATG 1 PRstop Rgenes phase1 overlap frequency phase 2 overlap frequency RATG phase1 ATG frequency phase2 ATG frequency Rstop phase1 stop codon frequency phase2 stop codon frequency Rgenes PRATG 1 PRstop 3.7 P6.4 1 P1 P 0.5 The expected value under no bias for overlaps in the two scenarios