Researchers led by Vanderbilt's Roger Cone¹, Ph.D., have discovered a new member of a gene² family that has powerful influences on pigmentation（色素淀积） and the regulation of body weight. The gene is the third member of the agouti（刺鼠） family. Two agouti genes⁴ have been identified previously⁵ in humans. One helps determine skin and hair color, and the other may play an important role in obesity⁶ and diabetes⁷.

The new gene, called agrp2, has been found exclusively in bony fish, including zebrafish, trout⁸（鳟鱼） and salmon⁹（鲑鱼） . The protein it encodes enables fish to change color dramatically to match their surroundings, the researchers report Oct. 27 in the early edition of the Proceedings¹⁰ of the National Academy of Sciences (PNAS).

"When my graduate student, Youngsup Song, discovered a third agouti protein in the fish pineal gland¹¹（松果腺） , an organ that regulates daily rhythms in response to light, we initially¹² thought we had found the pathway that regulates hunger diurnally¹³（每日） ," said Cone, chair of the Department of Molecular¹⁴ Physiology¹⁵ & Biophysics and director of the Vanderbilt Institute for Obesity and Metabolism¹⁶.

"That is the mechanism¹⁷ that makes you hungry during the day, but not at night," he continued. "However, Chao Zhang, a graduate student who followed up the study, ultimately discovered that this agouti protein … is involved in the rapid pigment³ changes that allow fish to adapt to their environment."

This phenomenon, called background adaptation, also has been observed in mammals. The coat of the arctic hare, for example, turns from brown in summer to white camouflage¹⁸（伪装，掩饰） against the winter snow.

In contrast to mammals that have to grow a new coat to adapt to a changing environment, fish, amphibians¹⁹（两栖动物） and reptiles²⁰（爬行动物） can change their skin color in a matter of minutes.

The first agouti gene, which produces the striped "agouti" pattern in many mammals, was discovered in 1993. The same year, Cone and his colleagues at Oregon Health Sciences University in Portland reported the discovery of the gene that encoded the melanocortin-1 receptor, a key player in the pigmentation story.

They demonstrated that the agouti protein prevented the melanocortin-1 receptor in melanocytes (pigment cells) in the skin from switching on production of black-brown pigment, and instead shifted the pigment to yellow-red hues²¹.

The second agouti gene encodes agouti-related protein (AgRP), which blocks a melanocortin receptor in the brain. It prevents the melanocortin-4 receptor from inhibiting²² food intake²³, and thus stimulates²⁴ eating.

In the current paper, Cone's group reports that the newly discovered protein, AgRP2, regulates expression of the prohormone（激素原） genes pmch and pmchl, precursors²⁶ to melanin-concentrating hormone²⁵, which has a pigment-lightening effect.

"Together, the versatile²⁷（通用的，万能的） agouti proteins and melanocortin receptors are responsible for regulation of body weight, the banded patterns of mammalian coats, and even red hair in most people," Cone said. The current work shows that agouti proteins are also involved in the camouflage mechanisms²⁸ used in thousands of fish species.