THE MACROMELANOPHORE LOCUS AND THE MELANOMA ONCOGENE XMRK ARE SEPARATE GENETIC ENTITIES IN THE GENOME OF XIPHOPHORUS

Fish of the genus Xiphophorus are polymorphic for black pigmentation p atterns. Certain intra- or interspecific hybrids exhibit enhanced expr ession of these patterns, leading in many cases to malignant melanoma. Because no recombination was ever observed between the pattern inform ation and the genetic predisposition to develop melanoma after hybridi zation, a ''tumor gene'' (Tu) was postulated that encodes both phenoty pes. A dominant oncogene, ONC-Xmrk, was then found to be necessary and sufficient for the transforming function of Tu. Here ive present mole cular evidence that ONC-Xmrk and the pigment pattern information are e ncoded by separate, although intimately linked loci. No ONC-Xmrk gene was present in the 15 Xiphophorus strains investigated which exhibit n o black pigmentation pattern. Five different patterns from Xiphophorus maculatus, X. evelynae, X. milleri, X. cortezi, and X. montezumae wer e associated with ONC-Xmrk and were melanomagenic, while fish of X. he lleri, X. variatus, X. nezahualcoyotl, and X. montezumae with five oth er patterns had no ONC-Xmrk and consequently did not produce hybrid me lanoma. These data provide evidence that ONC-Xmrk is sufficient for tu morigenesis in Xiphophorus hybrids, and that a separate, pigment patte rn-encoding locus is closely linked to it.