Table 1.

Functional and Phenotypic Characterization of the Eye-Development Genes Exhibiting Evidence of Adaptive Evolution in the Barn Owl Lineage

Gene (Protein)	Function	Eye-Related Phenotype	Adaptive Signatures	References
agtpbp1 (ATP/GTP binding protein 1)	agtpbp1 is a functional zinc-binding domain in the agtpbp1 is required for survival of neuron populations.	agtpbp1 is required to prevent photoreceptor degeneration in the retina.	() See text for details	Chakrabarti et al. (2008)
arid1a (AT-rich interactive domain-containing protein 1A)	arid1a is part of a large ATP-dependent chromatin remodeling complex, which is involved in transcriptional activation and repression of genes by chromatin remodeling.	arid1a mutants possess small optic cups compared with the wild type.		Chandler et al. (2013)
bcl11b (B-cell CLL/lymphoma 11B)	bcl11b is zinc finger transcription protein involved in cell proliferation, differentiation, and apoptosis.	bcl11b knockout mice are born with eyes open.		Kominami (2012)
bfsp2 (beaded filament structural protein 2)	bfsp2 is a structural gene involved in stabilization of lens fiber cell cytoskeleton.	Mutations in the bfsp2 gene are associated with cataracts and myopia susceptibility.		Song et al. (2009)
col5a1 (alpha 1 type V collagen)	col5a1 is a type V collagen, which forms heterotypic fibrils with type I collagen and accounts for 10–20% of corneal collagen.	Mutations in the col5a1 genes are associated with abnormally thin and steep corneas.		Segev et al. (2006)
crb1 (crumbs family member 1)	crb1 may be involved in the development of the cell polarization and adhesion in the retina.	Mutations in the crb1 gene are associated with severe retinal dystrophies, including the rod-cone dystrophy, also called retinitis pigmentosa.		Bujakowska et al. (2012)
ephb1 (ephrin receptor B1)	ephb1 is a receptor tyrosine kinase which directs the axonal path through interactions with ephrin-B-type proteins following axon-cell contact.	ephb1 is responsible for the retinal axon guidance, redirecting the retinal ganglion cells axons at the optic chiasm midline.		Chenaux and Henkemeyer (2011)
gabrr2 (gamma-aminobutyric acid receptor subunit rho-2)	gabrr2 encodes the rho2 subunits of the ligand-gated ion channels, which mediate fast synaptic inhibitory effects of the gamma-aminobutyric acid.	gabrr2 is expressed in the horizontal and bipolar cells of the retina and plays a role in retinal neurotransmission.		Marcos et al. (2000)
myo7a (myosin VIIA)	myo7a is a member of the myosin gene family, with actin-based motor activity. It is present in the retinal pigment epithelium where it plays an important role in regulating opsin transport in retinal photoreceptors.	Mutations in the myo7a result in Usher syndrome type 1B, which is characterized by progressive retinal degeneration.		Williams and Lopes (2011)
nphp4 (nephronophthisis 4)	rpgrip1 and nephrocystin-4 colocalize in the retina.	Mutations in nphp4 are associated with a combination of nephronophthisis and retinitis pigmentosa called Senior–Løken syndrome.		Won et al. (2011)
phactr4 (phosphatase and actin regulator 4)	phactr4 interacts with the regulator of protein phosphatase 1 that is required for neural cell migration during development.	phactr4 regulates neural tube and optic fissure closure.		Kim et al. (2007)
prom1 (prominin 1)	prom1 plays a role in early retinal development, acting as a key regulator of disk morphogenesis in photoreceptors.	Mutations in prom1 result in retinitis pigmentosa and cone-rod dystrophy.		Michaelides et al. (2010)
prox1 (prospero homeobox 1)	prox1 is a member of the homeobox transcription factor family that functions as a key regulatory protein in neurogenesis.	prox1 knockout mice have defects in the elongation of lens fiber cells. prox1 is also detected in differentiating horizontal, bipolar, and amacrine cells		Duncan et al. (2002), Dyer et al. (2003)
prph2 (peripherin-2)	prph2 encodes a photoreceptor-specific tetraspanin protein called peripherin-2, which is critical for the formation and maintenance of rod and cone outer segments.	Mutations in prph2 are associated with a variety of forms of retinitis pigmentosa and macular degeneration phenotypes.		Conley and Naash (2014)
rs1 (retinoschisin 1)	rs1 is an extracellular protein that plays a crucial role in the cellular organization of the retina.	Mutations in rs1 are associated with progressive retinal and macular degeneration, common phenotypes of retinoschisis disease.		Takada et al. (2008)
rxra (alpha retinoid X receptor)	rxra mediates the biological effects of retinoids by their involvement in retinoic acid-mediated gene activation.	rxra mutants show abnormal opening of the retina at the optic nerve exit point (optic disk coloboma) and also conformational alterations in the cornea and lens.		Mascrez et al. (2009)
slc4a5 (solute carrier family 4, member 5)	slc4a5 mediate sodium- and bicarbonate-dependent cotransport, regulating the intracellular pH.	slc4a5 knockout mice develop severe retinopathy, with loss of photoreceptors and ganglion cells, and retinal detachment.		Kao et al. (2011)
tbc1d20 (TBC1 domain family, member 20)	tbc1d20 encodes a GTPase-activating protein specific for Rab1 and Rab2 small GTPase families.	tbc1d20 mutations are associated with the Warburg Micro syndrome 4 that is characterized by eye cataracts (vacuoles present throughout the entire lens).		Park et al. (2014)
topors (topoisomerase I-binding arginine/serine-rich)	topors functions in proteasomal degradation pathway by acting as an E3 ubiquitin ligase for p53, and is involved in the photoreceptor development and function.	Genetic variants of topors were shown to cause a form of retinal degeneration (retinitis pigmentosa).		Chakarova et al. (2011)
wnt5b (wingless-type MMTV integration site family, member 5B)	wnt5b is a ligand for members of the frizzled family of seven transmembrane receptors and has a probable signaling role in the anterior eye-development.	wnt5b is expressed in the differentiating lens fiber cells.		Fokina and Frolova (2006)
aldh1a1 (aldehyde dehydrogenase 1 family, A1 member)	aldh1a1 act as an enzyme that catalyzes the oxidation of the retinol (vitamin A) metabolite, retinal, to retinoic acid, and also as a crystallin in the eye.	aldh1a1 knockout mice were shown to develop cataracts and being sensitive to UV-induced damage.		Chen et al. (2012)
hps1 (Hermansky–Pudlak syndrome 1)	hps1 encodes a protein that may play a role in melanosome biogenesis.	hps1 is associated with the Hermansky–Pudlak syndrome that is characterized by oculocutaneous albinism (iris transillumination).		Jardón et al. (2015)
jag1 (jagged 1)	jag1 encodes a ligand that participates in the Notch pathway of the lens, transducing cell contact-mediated communication and contributing to the lens progenitor cell proliferation and differentiation.	jag1 mutants have both lens progenitor cell proliferation and differentiation deficits.		Le et al. (2009)
pax2 (paired box 6)	pax2 is a transcription factor with a conserved DNA-binding paired box domain.	Mutations in pax2 can result in retinal coloboma syndrome manifested by the failure of optic fissure histogenesis and a damaged retina.		Stanke et al. (2010)
rab18 (member RAS oncogene family)	rab18 may play a role in the maintenance of the cytoskeleton in lens fiber cells.	Mutations in the rab18 cause Warburg Micro Syndrome characterized by defective ophthalmological phenotypes in lens development, such as congenital nuclear cataracts and atonic pupils.		Carpanini et al. (2014)

Note.—The function and the eye-related phenotypes of the listed eye-development genes were inferred from the GeneCards database (http://www.genecards.org/; Safran et al. 2010) and specific citations referenced below. Patterns of the evolution of these genes in the barn owl lineage are summarized in the table using colored circles: relaxed selection (red circle) and intensified selection (blue circle), pseudogenization (gray circle), and association with orbit convergence (black circle).