Table S2.

PANTHER pathways significantly overrepresented for genes with LOF variants

PANTHER pathway	Obs (Ref.)	Obs	Exp	Fold enrichment	Overrep P
Nicotine pharmacodynamics pathway	32	3	0.24	12.50	0.00192**
Dopamine receptor-mediated signaling pathway	54	3	0.41	7.32	0.00818**
Hedgehog signaling pathway	21	2	0.16	12.50	0.0112*
Nicotine degradation	3	1	0.02	50.00	0.0223*
Angiogenesis	145	4	1.09	3.67	0.0247*
Lysine biosynthesis	6	1	0.05	20.00	0.0442*
Blood coagulation	45	2	0.34	5.88	0.0458*

Among the 50 genes assigned to the dopamine pathway, LOF variants were found in PPP1CC (all eight animals heterozygous), KCNK3 (one hamadryas and two hybrids homozygous for the LOF variant, the others homozygous for the reference), and GNB1 (one hamadryas and one hybrid heterozygous for the LOF variant, the others homozygous for the reference). *P < 0.05; **P < 0.01.