A b/b (top) and a wild-type medaka fish. Courtesy of Shoji Fukamachi, University of Tokyo, Japan.

Sun worship might give you a great tan, but it is also behind the increasing incidence of skin cancer, especially among those of northern European descent. As a result, pigmentation biology has come under close scrutiny in recent years, and genetic studies into mouse coat-colour mutants and into human pigmentation disorders have revealed much about the melanin biosynthetic pathway. Now Japanese researchers have discovered a new component of this pathway, surprisingly not in mammals but in a fish — the medaka. This is the first medaka gene to be positionally cloned, and it promises to provide new insights into the biochemical regulation of melanin synthesis, not just in fish but possibly in humans too.

The Japanese have bred an attractive orange-red variety of medaka — which is homozygous for an allele called b — for hundreds of years. Melanin formation in b fish is barely visible, except in the eyes (see picture). To positionally clone b, Shoji Fukamachi and colleagues mapped it in a backcross derived from two highly polymorphic inbred strains — so polymorphic, in fact, that after mapping only 545 backcross progeny, they were able to narrow down the candidate interval to 40 kb. This region contained two genes, one of which was mutated in seven of eight B-locus mutants. No mutations were found in the common b allele, but given its tissue-specific effects, this might be because a mutation lies in the gene's upstream regulatory regions.

Importantly, this gene is highly homologous to the human gene AIM1 (antigen isolated from immunoselected melanoma 1). The medaka and human AIM genes, together with a mouse homologue isolated by the authors, are predicted to encode a 12 transmembrane-spanning protein. Because this is a structure common to transporter proteins, Fukamachi et al. propose that AIM1 might be located in the melanosomal membrane, where it could transport certain substances required for melanin biosynthesis. No doubt, future fishing trips into the medaka genome are planned — let's hope that they yield as rapid returns as this one.