Genetic switch between redundancy and synergyin a multicellular gene expression code

Giovanni Diana

MRC Centre for Developmental NeurobiologyKing’s College London

Quantitative Laws II13 June 2016

From environment to physiology

Environment

Gene expression

Physiology

daf-7 and tph-1 expression in sensory neurons of C. elegans

egg-5RNAi

BaselineBacteria Food ShiftWell Fed

40x

RNAi Food ShiftWell fedBaseline

food

Two g

enera

tions

Hatc

h Day of Adulthood

1 2 3 5 64L4

Imaging

Microfluidic system for high-throughputin vivo imaging of C. elegans

NSM ADF ASItph-1 tph-1 daf-7Gene:

Neuron:

Fluorescence images reporting tph-1/daf-7 promoter activities

Food Level (cells/ml)100 102 104 106 108 1010

Wild Typedaf-7(-)tph-1(-)tph-1(-);daf-7(-)

25

20

30

35

40

45

Mean L

ifesp

an (

days)

daf-7 and tph-1 regulate lifespan response to food in the environment

Food Level

tph−1 in ADFdaf−7 in ASI

tph−1 in NSMEx

pres

sion

Lev

el

Food Leveltph−1 variance in ADFdaf−7 variance in ASItph−1 variance in NSM

Vari

an

ce Wild type

daf-7 KO

daf-7 regulate expression noise.

Information theory and molecular genetics

Information encodedby each neuron Channel capacity

wholesum of parts

Info

rmat

ion

(bits

)

0

1

2

−0.4

0.4

Frac

tion

ofR

edun

dant

Info

rmat

ion

−0.4

0.4

Red

unda

ncy

Syne

rgy (b

its)

wild-typ

e

tph-1(

–)

daf-7

(–)

tph-1(

–); da

f-7(–)

Info

rmat

ion

Whole Sumof Parts<

Redundancy

Whole Sumof Parts>

Synergy

ASI

ADF

NSM

Combinationof NSM, ASI,and ADF Si

gnal

Cor

rela

tion

(bits

)

0

0.4

0.8

0.4

0

wild-type

daf-7(-)

tph-1(-)

tph-1(-);daf-7(-)

Sig

nal C

orr

ela

tion

Noise Correlation

input

output

= {0,1}

S1 S2 S3

= αS1+ βS2+ γS3

Sensors

0.0 0.5 1.0 1.5 2.00.0

0.2

0.4

0.6

0.8

1.0

Signal/Noise Ratio, σ3/a

Frac

tion

daf-7 is required to maintaina redundant coding strategy

SynergyRedundancy

Information transmitted by3-node gaussian networks

Constraining information generates synergy switches at low SNR

single and double mutants display high noise correlation

Conclusion and Outlook

I The ADF-ASI-NSM network provides a robustcode for food abundance in the environment.

I daf-7 is required to maintain redundancy in theencoding.

I How does the system perform at differenttemperatures.

I Link coding strategy to network topology.

Acknowledgements

KCLDr. QueeLim Ch’ngDr. Eugeni V. EntchevDr. Dhaval S. PatelOwen LeyshonKatherina Gers-BarlagBrian HandleyHale Tunbak

Georgia Institute ofTechnology:Dr. Hang LuDr. Mei Zhan