Medaka on the move

Long before it found favor with geneticists—long before there were geneticists, in fact—the Japanese medaka (Oryzias latipes) was bred by hobbyists throughout Japan. As shown here in an 1843 drawing by Bai-en Mohri, there are differently pigmented strains of medaka that enhance their aesthetic appeal, including those now recognized as wildtype (brown) and mutant (orange-red and white) varieties. The orange-red medaka harbors a mutation at the b locus, and on page 381, Shoji Fukamachi and colleagues¹ describe a series of mutations in a new gene at this locus, encoding a putative sucrose transporter. The identification of the molecular lesion(s) in the b mutant is not only of historical interest, but also marks the first positional cloning of a gene in this model organism.

Credit: This image is reproduced with kind assistance from Hidetomo Kajita of the National Diet Library and Koichi Nakamura of Nature Japan.

It has already been a good year for medaka mavens. Results reported in the last 12 months include: high-efficiency generation of embryonic mutants in ethylnitrosourea-based screens², a detailed linkage map³, evidence for de novo transposition of the medaka Tol2 transposable element⁴, cloning by nuclear transfer⁵, and construction of a bacterial artificial chromosome (BAC) library derived from the inbred Hd-rR strain⁶. The medaka has also had its share of historical firsts, most notably as the first vertebrate in which Mendelian inheritance was demonstrated⁷, and, in a less weighty turn, as the first vertebrate to reproduce successfully in microgravity⁸. The merits of medaka as an experimental organism have been summarized⁹, and the recent flurry of reports, including that of Fukamachi and colleagues¹, suggests that a critical mass of essential genetic resources has at last been assembled (see http://biol1.bio.nagoya-u.ac.jp for a compendium of medaka resources).

The b mutant analyzed by Fukamachi et al. lacks melanin pigment in its melanophores, but its orange, white and silver chromatophores are normally pigmented, resulting in the characteristic orange-red color. The b locus was previously narrowed down to a manageably small candidate region, and was cloned by recombination mapping between two medaka strains that are highly polymorphic, an effort that was facilitated by the recently published BAC library⁶. Seven of eight b alleles have mutations in the coding region; the lone exception is the original b mutant, which may have a mutation in a regulatory element.

What is B? Results from database queries predict a 12-pass integral membrane protein. It seems to be expressed in melanophores, but not exclusively, suggesting a possible function outside of melanogenesis. Indeed, as mouse pigmentation mutants have been a boon to vertebrate biology¹⁰, providing insight into several cell lineages, there is ample precedent for such proteins to have a number of roles. The biggest hint in regard to B comes from its 23% amino-acid sequence identity with plant sucrose transporters. Fukamachi et al.¹ have put forward a plausible scenario whereby sucrose transport could affect melanin synthesis, but a real understanding of the origin of the orange-colored medaka awaits functional studies on the B protein. At the very least, however, it's a pleasing and appropriate coincidence that B might have a role in sugar metabolism. If the medaka put Mendel on the map with respect to vertebrate genetics, recall one of the original sources of Mendel's laws: the pea plant r locus, which encodes a starch-branching enzyme that determines whether pea seeds are round or wrinkled¹¹.