Corn snakes are famous for their dazzling colors and intricate patterns, yet the genetic basis of their variations has long been a mystery. Now, researchers at the University of Geneva have uncovered the role of a single gene, CLCN2, in shaping these patterns, shedding light on how snakes develop their distinctive appearances.
Corn snakes, Pantherophis guttatus, owe their striking colors to chromatophores—skin cells containing pigments or light-reflecting structures. The typical corn snake sports an orange background with red blotches outlined in black and a black-and-white checkered belly. However, certain genetic morphs create unique variations.
Among them, the Motley morph features fused or broken dorsal spots forming a linear pattern, while the Stripe morph showcases continuous stripes running along its back. Both share an unusual trait—a plain belly without a checkered pattern.
Scientists conducted crossbreeding experiments between Motley and Stripe snakes to investigate the genetics underlying these variations and sequenced the genomes of their offspring. Their results revealed that both morphs are linked to mutations in CLCN2, a gene responsible for transporting chloride ions across cell membranes, affecting cellular communication.
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CLCN2’s expression is significantly reduced in Motley snakes rather than being mutated directly. However, in Stripe snakes, a small DNA fragment called a transposon inserts itself into the gene, rendering it non-functional.
“This discovery was unexpected, as in humans and mice, the CLCN2 gene plays a critical role in brain function, and mutations are linked to serious conditions such as leukoencephalopathy,” explained Sophie Montandon and Pierre Beaudier, co-first authors of the study. “Yet in corn snakes, the gene influences skin patterns instead of neurological activity.”
Researchers genetically inactivated the CLCN2 gene to confirm its role, resulting in stripe-patterned mutants—definitive proof of its involvement in color pattern formation.
Further investigations revealed that CLCN2 is active in the adult brain, like in mice and humans, but also plays a key role in chromatophores during embryonic development. In mutant snakes, these pigment cells fail to cluster into blotches and instead align into stripes.
“Our results show that a mutation in the CLCN2 gene in corn snakes does not cause neurological or behavioral disorders. However, the protein plays an essential, and previously unknown, role in developing skin coloration patterns,” said Asier Ullate-Agote, co-first author of the study.
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The next research phase will examine the impact of CLCN2 on chromatophore interactions more closely, aiming to decipher the cellular mechanisms underlying the diverse coloration observed not only in corn snakes but also in other reptiles.
This discovery opens new doors for understanding how genetic mutations shape natural patterns, offering broader insights into evolution and biodiversity in the animal kingdom.
Journal Reference:
- Montandon, S.A., Beaudier, P., Ullate-Agote, A. et al. Regulatory and disruptive variants in the CLCN2 gene are associated with modified skin color pattern phenotypes in the corn snake. Genome Biol 26, 73 (2025). DOI: 10.1186/s13059-025-03539-0
