Mate choice for more melanin as a mechanism to maintain a functional oncogene

Abstract

The mechanisms by which cancer evolves and persists in natural systems have been difficult to ascertain. In the Xiphophorus melanoma model, a functional oncogene (Xiphophorus melanoma receptor kinase Xmrk) has been maintained for several million years despite being deleterious and in an extremely unstable genomic region. Melanomas in Xiphophorus spp. fishes (platyfishes and swordtails) have been investigated since the 1920s, and, yet, positive selection that could explain the maintenance of Xmrk has not been found. Here, we show that Xiphophorus cortezi females from two populations prefer males with the spotted caudal (Sc) melanin pattern, which is associated with the presence of the Xmrk oncogene and serves as the site of melanoma formation within this species. Moreover, X. cortezi females prefer males with an enhanced Sc to males with a reduced Sc pattern. RT-PCR analysis confirms tissue-specific Xmrk expression within the Sc pattern in X. cortezi. Because of the association of Xmrk with the Sc pigment pattern and the fact that melanoma formation augments this visual signal, sexual selection appears to be maintaining this oncogene because of a mating preference for Sc, as well as the exaggeration of this male trait. At the individual level, decreases in viability and fecundity because of Xmrk and subsequent melanoma formation may be mitigated via increases in mate acquisition. At the population level, maintenance of this oncogene appears to be under frequency dependent selection, as we detected female preference for males without Sc in a third population that had higher frequencies of Sc in females.

Fig. 1.

Xmrk and protooncogene expression in X. cortezi. Semiquantitative RT-PCR analyses using the same template primers for the oncogene (Xmrk, bottom bands of upper image) and protooncogene (top bands of upper image). In each of the three wild-caught individuals, all of which did not have visible melanoma formation, the Sc tissue was associated with both Xmrk and protooncogene expression, whereas in the nonpigmented control tissue (C), only the protooncogene was expressed. The housekeeping gene, β-actin, is included as a loading control (17). A 15-bp insertion associated with the protooncogene in X. cortezi accounts for the fractionation of the two bands by gel electrophoresis (A.A.F. and S. Tanda, unpublished data). This small insertion was found in the predicted signal peptide sequence at the beginning of the protooncogene. Polymorphisms within this region of the oncogene and protooncogene are common in individuals derived from wild populations of several Xiphophorus spp. (18).

Fig. 2.

Sc phenotype in X. cortezi. (A) X. cortezi male collected from Tanute, with an average expression of Sc on the caudal fin (nonmalignant). (Scale bar, 5 mm.) (B) X. cortezi male from Conchita with malignant melanoma extending from Sc into the caudal peduncle. Histopathology confirms malignant melanoma in this individual, classified as a melanophorous-macromelanophorous polymorphic melanoma (20 and A.A.F. and P. Bowser, unpublished data). Note on this male that substantial portions of the sword and caudal fin have sloughed-off, which ultimately impairs swimming ability. Specimens were photographed on the day they were collected in December 2005. (Scale bar, 5 mm.)

Fig. 3.

Female preferences for enhanced Sc phenotypes. The time that females from the Cebolla population spent associating with the large Sc treatment compared with the small Sc treatment, as well as with an average size Sc compared with no Sc. Bars represent the mean ± SEM.

Fig. 4.

Female preferences for Sc across populations. Primary y axis (left, gray bars) represents the mean amount of time females spent with painted Sc males minus the time spent with the non-Sc males across all four trials. Bars represent the mean ± SEM. Positive values indicate preference for Sc males, whereas negative values indicate discrimination against Sc males. Secondary y axis (right, white bars) represents the proportion of females with Sc phenotype for each of the three populations (all Cebolla females lacked Sc).