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.

Documents

Transcript of Phase Bias in Niv Sabath University of Houston Overlappin enes g.