Tetrapods express one agouti gene [agouti signaling protein (asip)] in the skin regulating pigmentation and a second [agoutirelated protein (agrp)] in the brain regulating energy homeostasis. In contrast, most teleosts have four genes encoding agoutitype proteins. Braasch and Postlethwait (1) present an analysis of the evolutionary history of agouti genes in teleosts, reordering the phylogenetic tree proposed previously (2) and proposing a nomenclature change. However, gene nomenclature derives mainly from functional or sequence properties and not from evolutionary predictions. Furthermore, inclusion of an ancient agouti sequence from the elephant shark provides an additional interpretation of the phylogeny (Fig. 1). The word agouti, from the Guaraní language of South America, refers to rodents (genus: Dasyprocta) noted for prominent-banded pigment patterns in individual hair shafts. The term agouti came to be used to describe mutations in tetrapods that impacted this banding pattern. The agrp gene, discovered later, encodes a protein in hypothalamic neurons, and zebrafish agrp shares the same distribution of expression, regulatory properties, and function with the mammalian protein of the same name. More recently, we showed that a zebrafish gene called agrp2, a teleost-specific agouti family member expressed in the pineal, controls expression of hypothalamic melaninconcentrating hormone genes (pmch and pmchl) and regulates background adaptation (3).

In teleosts, an ancient duplication produced four agouti genes. asip2 and agrp2 (4) were initially called A2 genes, and their cysteine motifs start with C6C5CC... rather than C6C6CC... found in both agrp and asip. The analysis by phylogeny and synteny of teleost agouti genes (2) suggested that agrp and agrp2 shared synteny with mammalian agrp and were paralogous genes derived from the teleost genome duplication. After the