phase bias in niv sabath university of houston overlappin enes g

Phase Bias in

Niv SabathUniversity of Houston

Overlappinenes g

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

Overlap Length

Count

Long Overlaps Short Overlaps

T G AT A AT A G

5’ 3’Phase 1Phase 2

Phase 0

Same-Strand Overlaps

Overlap Length

Count


T G AT A AT A G


Phase 0


1

Overlap Length

Count


T G AT A AT A G


Phase 0


2

Overlap Length

Count


T G AT A AT A G


Phase 0


4

Overlap Length

Count


T G AT A AT A G


Phase 0


5

7Overlap Length

Count


T G AT A AT A G


Phase 0


Overlap Length

Count


T G AT A AT A G


Phase 0


8

10Overlap Length

Count


T G AT A AT A G


Phase 0


Overlap Length

Count


T G AT A AT A G


Phase 0


11

Overlap Length

Count



Phase 0

T A G C A T G T A T C A T G G

“…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.”(Cock and Whitworth 2007)

170 bacterial genomes15298 long overlaps in phase 1 4153 long overlaps in phase 2


170 bacterial genomes15298 long overlaps in phase 1 4153 long overlaps in phase 2

Composition?


Scenarios of overlap creation

5’ 3’

5’ 3’

5’ 3’


HypothesisThe 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


We examined the frequencies of ATG, the most common start codon, and stop codons in phase 1 and phase 2 reading frames



Met

Met

T G T

T G C

T G A

T G G

Cys

Cys

Stop

Trp

T A T

C A T

A A T

G A T

Tyr

His

Asn

Asp

5’ 3’ Phase 0

Phase 1

Phase 2


What causes the difference in ATG frequencies?

What causes the difference in ATG frequencies?

Relative abundance of amino acids


T G T

T G C

T G A

T G G

Cys

Cys

Stop

Trp

T A T

C A T

A A T

G A T

Tyr

His

Asn

Asp

Phe Leu Ile MetVal Ser Pro ThrAla Gln Lys GluArg Gly

Phase 1 Phase 2


The frequencies of ATG are correlated with the expected frequencies

00GNNNAT ff

00TGNNNA ff

r2 = 0.93

r2 = 0.80

Amino-acid frequency

ATG frequency

Phase bias


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:

Phase 1 + phase 2

Phase 1

Phase 2 (64% ATGA)

Stop codon usage:

TGA TAA TAG

What is the proportion (P) of overlaps, which are created by each scenario after accounting for ATG frequencies?

frequencyoverlapphasefrequencyoverlapphaseRgenes 2

1

frequencyATGphasefrequencyATGphaseRATG 2

1

frequencycodonstopphasefrequencycodonstopphaseRstop 2

1


1


1


1

stopATGgenes RPPRR 1


1


1


1

stopATGgenes RPPRR 1

5.0114.67.3 PPP

The expected value under no bias for overlaps in the two scenarios

phase bias in niv sabath university of houston overlappin enes g

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