Is behavior caused by genes or environment?


Can the environment influence the function of genes?

Gene sequence is inherited (you’re stuck with what you have)

However:Gene expression is influenced by inheritance AND age, tissue type, physical environment and social environment

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protein

messenger RNA(mRNA)

“gene expression” = mRNA abundance

gene

gene

Variation in gene sequence (DNA polymorphisms) can be found by “gene mapping” and DNA sequencing

Variation in gene expression can be found using “microarrays”



protein

messenger RNA(mRNA)

“gene expression” = mRNA abundance

gene

atgtcagccgataactgactgatggtaaattgagtttt

DNA polymorphism

Microarrays measure mRNA abundance for 1000s of genes simultaneously

Behavioral division of labor in the honey bee colony


10 20 30 40

% old foragers in colony

10

20

30

40

50

% i

ntr

od

uce

d b

ees

that

in

itia

ted

fo

rag

ing

by

day

14

Age at onset of foraging is socially regulated


Age at onset of foraging is socially regulated

Inhibitory social pheromone

Nurse Forager


Age at onset of foraging is also genetically variable

m lc

m

m lc

c

m lc

l

Introduced bees

Host colony

% o

f in

tro

du

ced

bee

s fo

rag

ing

at

15 d

ays

of

age

60

40

20

0

m, c and l are different genetic strains

Each pair of spots is a “detector” for mRNA abundance for 1 bee gene.

We can analyze mRNA abundance for ~5500 different genes at the same time (in a single dissected bee brain)

Honey bee brain microarray

Comparing gene expression in a nurse brain vs. a forager brain

Nurse mRNA level

Fo

rag

er m

RN

A l

evel

Dissectednurse brain

microarray hybridization

Dissectedforager brain

labeling reaction

Do age-related changes in behavior involve changes in gene expression in the brain?

~700 one-day-old bees(marked)

“Typical” host colonies(ca. 40,000 mixed-age bees)

Collect marked bees

day 7 day 30

Youngnurses(n = 18)

Old foragers(n = 18)

YN OF

Gen

es

Bee brains

Yellow = high mRNA abundance

Blue = low mRNA abundance

YN = young nurseOF = old forager

About 1/3 of genes expressed in the bee brain show differences in expression!

But…Are gene expression differences really associated with behavior differences or with age?

YN OF

Gen

es

Bee brains



YN = young nurseOF = old forager

About 1/3 of genes expressed in the bee brain show differences in expression!

Changing age-demography in the colony (i.e., social environment) allows us to collect “precocious” young forgers and “over-aged” old nurses

~1500 one-day-old bees(marked)

All bees are same age!!!

Collect marked bees

day 7 day 30

Youngnurses(n = 6)

Old nurses(n = 6)

Youngforagers(n = 6)

Old foragers(n = 6)

YN OF YN ONYF OF

Gen

es

Bee brains



YN = young nurseYF = young foragerON = old nurseOF = old forager

Gene expression was primarily associated with behavior, not age!

YN OF YN ONYF OF

Gen

es

Bee brains



YN = young nurseYF = young foragerON = old nurseOF = old forager

>21.5

1.251

0.80.67<0.5

Although 1/3 genes show differences, only ~50 genes are needed to “predict” whether a bee is a nurse or a forager(Whitfield, Cziko & Robinson. Science 2003, 302: 296)

Y = young (7 ±2 days)O = old (30 ±2 days)N = NurseF = Forager

Typical colonybees

Single-cohort (age-matched)

bees

mR

NA

le

vel

Is gene expression in the brain a cause or consequence of behavior?

Brain gene expression• Upstream regulation of behavior

Behavior

Brain gene expression• Consequence of behavioral activity, experience or environmental differences

?

?Behavior

-- or --


Manipulate gene expression in brain

Effects on behavior?

Direct test of causation:


Direct test of causation:

Manipulate gene expression in brain

Effects on behavior?

Can’t do th

is yet –

need transgenics!!!


Brain gene expression• Upstream regulation of behavior

Behavior

Brain gene expression• Consequence of behavioral activity, experience or environmental differences

?

?Behavior

-- or --

Brain gene expression in the absence of task-related experience

Caged bees(no task-related

experiences)


Social cue or treatment that

accelerates the onset of foraging

Forager-like changes in brain gene expression?


experiences)


Social cue or treatment that

accelerates the onset of foraging

Social cue or treatment that delays the onset of foraging

Forager-like changes in brain gene expression?

Nurse-like changes in brain gene expression?


experiences)

High in foragers

(32)

High in nurses

(18)

Induced by methoprene

(249)13 0

Repressed by methoprene

(222)0 11

Treat with methoprene(JH analog)


experiences)

Juvenile hormone analog (methoprene) accelerates the onset of foraging and causes forager-like changes in brain gene expression (in the absence of experience)

“marker” genes

Whitfield CW et al. PNAS. 2006. Oct 31; 103(44):16068-75.


experiences)

Treat with QMP

High in foragers

(32)

High in nurses

(18)

Induced by QMP (602)

0 4

Repressed by QMP (704)

18 2

Queen mandibular pheromone (QMP) delays the onset of foraging and causes nurse-like changes in brain gene expression (in the absence of experience)

“marker” genes

Grozinger CM, Sharabash NM, Whitfield CW, Robinson GE. PNAS. 2003. Nov 25; 100:14519


Can the environment influence the function of genes?

Nurse

Comb-b

uilder

GuardUnderta

ker

(corp

se-rem

over)

Forager

Many behaviors… but how many involve gene expression differences?

> 21.5

1.251

0.80.67< 0.5

Gen

e cl

ust

ers

(exp

ress

ion

lev

el i

n b

rain

)

Are gene expression changes robust at the level of individual?

Can gene expression profile in an individual bee’s brain be used to correctly predict behavioral group?

Method:

1. Computer identifies a set of “predictor genes” for behavior using expression data from the 59 bees in the “training set.”

2. Computer attempts to classify the single “test” bee based on its expression of the predictor genes.

3. Repeat iteratively for all 60 individual bees.

Result:

Computer can correctly assign behavior group for 57 out of the 60 bees.

“Training set”59 bees

(computer knows behavior)1 bee

(computer attempts to

classify)

“Leave-one-out” cross-validated class prediction

“Test set”

nurse or forager?

Is behavior caused by genes or environment?

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