TABLE 3.

Comparing the effects of the orthologous-gene expression changes on rheumatoid arthritis (RA) in humans and during the divergence of domestic and wild animals from their nearest common ancestor.

Humans					Animals
Gene	Effect of gene expression change (Δ) on RA, i.e., either contributes to (↑) or relieves (↓)				DEG	RNA-Seq		Δ During divergence from the nearest common ancestor
	Deficit	RA	Excess	RA		log2	PADJ	Deficit	Excess
					Tame vs. aggressive foxes (Hekman et al., 2018)
ESR2	Less ESR2-dependent suppression (Armstrong et al., 2013)	↑	More ESR2-dependent suppression (Armstrong et al., 2013)	↓	Esr2	−0.3	0.05	Domestic	Wild
IL1R2	More inflammation (Ocsko et al., 2018)	↑	Less inflammation (Ocsko et al., 2018)	↓	Il1r2	−0.4	0.05	Domestic	Wild
IL9R	Less inflammation judging by fibroblast-like synoviocytes (Raychaudhuri et al., 2018)	↓	More inflammation judging by fibroblast-like synoviocytes (Raychaudhuri et al., 2018)	↑	Il9r	0.4	0.05	Wild	Domestic
NPY	Lower risk of obesity-caused RA (Stofkova et al., 2009)	↓	Higher risk of obesity-caused RA (Stofkova et al., 2009)	↑	Npy	0.4	10–2	Wild	Domestic
TGFB2	Better recovery from RA (Um et al., 2018)	↓	Inhibited bone repair in RA (Um et al., 2018)	↑	Tgfb2	0.5	10–2	Wild	Domestic
					Domesticated vs. wild rabbits (Albert et al., 2012)
F7	Higher risk of hemorrhagic forms of RA (Thornorsteinsson et al., 2004)	↑	Recombinant F7 is a drug in hemophilia comorbid with RA (Drobiecki et al., 2013)	↓	F7	−2.7	0.05	Domestic	Wild
					Guinea pigs vs. cavies (Albert et al., 2012)
CCR6	Relieved RA (Bonelli et al., 2018)	↓	Higher risk of RA (Jatczak-Pawlik et al., 2020)	↑	Ccr6	2.2	0.05	Wild	Domestic
CETP	CETP deficiency promotes mortality in RA (Ferraz-Amaro et al., 2013)	↑	Higher risk of RA (Kim et al., 2016)	↑	Cetp	2.1	10–3	Wild	Domestic
IL1B	Relieved RA (Rzepecka et al., 2015)	↓	Circadian pain in RA (Olkkonen et al., 2015)	↑	Il1b	2.3	10–2	Wild	Domestic
PDYN	Pain hypersensitivity (Zheng et al., 2014)	↑	Pain resistance (Zheng et al., 2014)	↓	Pdyn	0.9	10–2	Wild	Domestic
					Dog vs. wolf (blood) (Yang et al., 2018)
HBB	Thalassemia-related osteoporosis worsens RA (Giakoumi et al., 2005)	↑	Hemolytic-origin extracellular HBB releases thrombogenic heme that adds to RA-related thrombogenesis (Bisoendial et al., 2010; Gall et al., 2018)	↑	Hbbl	−5.9	10–8	Domestic	Wild

log₂: differential expression of a gene of pets normalized to that in wild animals (log₂ units).