A

0 5 10 15

−5

0

5

Mean final abundance

Mea

n gr

owth

rate

CBR1

COX5BPOR2

COX12

XDJ1

AAC1

POR1

SWI4

CHD1RTF1

SDS3

ARP4SWI3

YKU80

ISW2

cytoplasmic translation∆ haploinsufficient genesmitochondrialchromatin

C

RTG3RTG2RTG1

−40

4Z Score

YPD

Sorbito

lHea

t

YPD + EtO

H

YP + EtO

H YPD

Sorbito

lHea

t

YPD + EtO

H

YP + EtO

H

S. cerevisiae Hybrid

D

0 20 40 60 80 100 120 1400

5

10

15

20

25

30

Hours

Gen

erat

ions

WTdMKS1dRTG2TDH3−RTG2

3.5 14.5 22 3.5 14

.5

−5 0 5 10

Generations

Barcode reads(normalized,log2)

23

essentialhaploinsufficient

Mitochondrial import and oxydative phosphorylation

Chromatin remodelers

Cytoplasmic translation and/or haploinsufficient genes

S. cerevisiae A S. cerevisiae B

RPO26SEC23SUI3RPL33ARPL5NOG1RPL20BRPS10ANOG2RPS3NIP1RPL20ARPL13BRNA14RPS18BRPL6BRPS1ARPS28BUTP13RPL10RPS4ASUI2IST3CCT2THS1RPL34BUTP9NMD3RPP1RPS20RPS24ARPL12BRPS13RPS11ASSB1RPL21ARPB5FES1RPL32RPL19B

YTA7NHP10YKU80GCN5SDS3CHD1RTF1ISW2ARP4SWI4SWI3NOP1

QCR10CIR1AIM11GPG1MSS18MRP51RSM25RSM22CBR1COX5BCOX12TIM12AAC1XDJ1POR2POR1

BFIGURE S4