Researchers have identified the genetic reason behind the orange fur in domestic cats, a mystery that has persisted for decades. Two teams, one led by Greg Barsh at Stanford University (United States) and another by Hiroyuki Sasaki at Kyushu University (Japan), have pinpointed a specific gene responsible for this trait. Their studies, published as preprints on bioRxiv, conclude that the orange color in cats is linked to a mutation in the ARHGAP36 gene located on the X chromosome.
This discovery provides valuable insight into pigmentation genetics and how genes regulate color patterns in mammals.
To understand this finding, it is crucial to explain how fur color is formed in mammals. Two primary pigments are responsible for fur coloration: eumelanin (black/brown) and pheomelanin (orange). The balance between these pigments determines the fur color.
In most mammals, this process is regulated by the MC1R gene (melanocortin-1 receptor), which acts as a switch. However, in cats, this mechanism operates differently, which has puzzled scientists for years.
Cats possess a special gene known as the orange locus (O/o), which controls the production of pheomelanin and eumelanin. This gene is not linked to MC1R but resides on the X sex chromosome.
The inheritance of orange color in cats is particularly interesting as it is related to the X chromosome. Female cats can display varied color patterns due to a phenomenon called X-chromosome inactivation. During embryonic development, each cell randomly inactivates one of its X chromosomes, leading to a mix of the O and o alleles, resulting in the unique fur patterns seen in tortoiseshell and calico cats.
Until now, the specific gene behind the orange locus was unknown. Recent studies have identified ARHGAP36 as the responsible gene, which functions by influencing a protein called protein kinase A (PKA). When ARHGAP36 is active, it inhibits PKA, which normally promotes eumelanin production. Thus, when ARHGAP36 operates, eumelanin production is blocked, allowing pigment cells to produce only pheomelanin, leading to the characteristic orange fur.
The Stanford team discovered that orange cats exhibit a genetic deletion in a regulatory region of the ARHGAP36 gene. This mutation causes abnormally high expression of the gene, blocking dark pigment production and favoring pheomelanin, resulting in orange fur.
The conclusion was reached through examinations of embryonic skin samples at various developmental stages. Scientists noted that embryos destined to become orange cats showed unusually high levels of ARHGAP36 expression, indicating a direct link between this gene's activity and fur coloration.
Furthermore, genetic sequencing of over 400 cats from various backgrounds revealed that all orange and calico cats shared the same mutation in ARHGAP36, establishing a clear genetic link between the mutation and specific fur coloration.
The robustness of this finding was reinforced by the independent conclusions reached by both research teams in the United States and Japan, validating the results and highlighting the importance of collaborative efforts in science.
Even seemingly simple mysteries, like a cat's fur, can conceal fascinating complexities that reveal fundamental biological principles.