Belize and Sibun Rivers of British Honduras. Zoologica 55: 1-. 16. KALLMAN,. K. D., 1975 The platyfish, Xiphophorus maculatus, pp. 81-132 in Handbook of ...
Copyright 0 1991 by the Genetics Society of America
Letter to theEditor Does Xmrk an Interesting Spot? The sex-linked P locus is an important regulatory gene that causes changes in the time to and weight at sexual maturity, in fertility and survivorship of poeand BORKOSKI ciliidfishes (KALLMAN,SCHREIBMAN 1973; KALLMAN and SCHREIBMAN 1973; KALLMAN and BORKOSKI 1978;KALLMAN1989).It is not known whether the P locus is active in all cells thereby speeding or retarding development in general, or specifically expressed in the tissues functionally related to sexual maturation (BAO and KALLMAN 1982; HALand SCHREIBMAN1983; KALLMAN PERN-SEBOLD 1989).The P locus appears to be tightly linked to the macromelanophore and pterinophore loci. A novel putative receptor tyrosine kinase gene of the EGF subfamily, Xmrk, maps near themacromelanophore and pterinophoreloci on thesex chromosome et al. of the platyfish (SCHARTL1990; WITTBRODT 1989).The Xmrk oncogene is involved in the development ofmelanomaswhen autosomal repressor genes are lacking in backcross to Xiphophorus helleri. Nearby, a copy of this gene is found in all species of the genus Xiphophorus independent of the Xmrk oncogene. They suggest this copyis the Xmrk protoncogene but write that “thenormal physiological function of Xmrk encoded R T K is beyond speculation” (WITTBRODT et al. 1989)or that “Its physiological function 1990). is currently unknown” (SCHARTL The genetic maps ofthe Xiphophorus chromosome offered by WITTBRODTet al. (1989)and SCHARTL (1 990)are cen-P-1%-Zr-(Pt-Dr)-0.03%-(Tu-Sd)-ter and cen-P-(Zr-Pt)-Tu-ter,respectively, where P is sexual maturation locus, Zr refers to iris red, (Pt-Dr) is the pterinophore locus alleledorsal red and (Tu-Sd) is the tumor locus associated with the macromelanophore allele Sd and the physical distance is represented by the recombination fraction between them. The placement of the P locus is not correct. The sex maturation locus P involved inthe timing of sexual maturation is not the sex determining locus (m,s) that plays an important role in determining maleness and 1937;KALLMAN femaleness in these fishes (GORDON 1970, 1975, 1984). The sex-determining locus is located at the proximal end of the chromosome near the centromere having a recombination frequency of 1 % with the macromelanophore locus (GORDON 1937; KALLMAN1970, 1975, 1984; ANDERS,ANDERSand KLINE 1973).A more correct map of the positions of the loci on the sex chromosome of Xiphophorus would be cen-(m,f)-Pt-M-Tu-P-ter,where the M repGenetics 128: 655-656 (July, 1991)
resents the macromelanophore pattern locus and ( m J ) is the sex determining locus. It is impossible to place the P and the Tu (the oncogene Xmrk) and the Xmrk proto-oncogene loci exactly as they allappear to map close to the pterinophore and themacromelanophore loci, which are themselves very tightly linked. Only one possiblecrossoverbetween the macromelanophore and/or the pterinophore loci and the P locus has ever been reported (KALLMANet al. 1973;KALLMAN 1989) and no recombinants were obtained between the macromelanophore and pterinophore loci by SCHARTL (1 990). Perhaps the P gene is the proto-oncogene Xmrk. If so, what would be the normal physiological action of this tyrosine kinase receptor? Recently, the Let-23 locus of Caenorhabditis elegans has been identified as a tyrosine kinase receptor gene (AROIAN et al. 1990).It encodes the receptor for the vulval inductive signal. Its general architecture is very similar to that of Xmrk. It is not known whether Let23 is expressed in other tissues and is involved inother inductive events. It is tantalizing to speculate that the proto-oncogene Xmrk plays a role in genital induction in the fish asLet-23 does in the worm. Indeed, epidermal growth factor acts as a potent mediator of estrogen-induced growth and differentiation of the mouse genital tract (NELSON et al. 1991).Furthermore, normal tyrosine kinase receptor genes are associated with mitogenic responses and are related to the mechanisms of cell growth (ULLRICHand SCHLESSINCER 1990). The credibility of the hypothesis that Xmrk protooncogene is the P locus depends upon the correctness of the genetic map of poecilliid fishes. This map is rapidly improving as more workers discover the intrinsic scientific interest of these minute vertebrates (MORIZOT 1989;MORIZOTet al. 1991). If the proto-onocogene Xmrk is the P locus, then each variant for time of sexual maturity should be represented by a DNA sequence variantsof Xmrk proto-oncogene. Congenics that differ in time to maturity should show differences in restriction fragment length polymorphism haplotypes for the Xmrk protooncogene and mutis mutandis. Furthermore this prediction can be tested by sequencing the Xmrk gene associated withdifferent P genotypes. The site ofgene action of the P locus might be the presumptive gonad of the embryo or its action might be expressed gen-
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erally, causing the heightening of the mitogenic activity of the early maturing genotypes. SOHN Department of Molecular Cell Biology Rockefeller University New York, New York 10021-6399
JOEL JAY
LITERATURECITED AROIAN,R. V., M. KOGA,J. E. MENDEL, Y. OHSHIMA and P.W. STERNBERG, 1990 The let-23 gene necessary for Caenorhabditis elegans vulval induction encodes a tyrosine kinase of the EGF receptor subfamily. Nature 348: 693-698. ANDERS, A., F. ANDERS and K. KLINE,1973 Regulation of gene expression in the Gordon-Kosswig melanoma system pp. 3363 in Genetics and Mutagenesis of Fish, edited by J. H. SCRODER. Springer-Verlag, New York. BAO, I. Y., and K. D. KALLMAN,1982 Genetic control of the hypothalamo-pituitary axis and the effect onsexual maturation (Xiphophorus, Pisces, Poeciliidae).J. Exp. Zool. 200: 297-309. GORDON, M., 1937 Genetics of Platypoecilus. 3. Inheritance of sex chromosomes in the platyfish. Genetics 22: 376-392. 1983 Ontogeny HALPERN-SEBOLD, L. R., and M. P. SCHREIBMAN, of centers containing luteinizing hormone-releasing hormone in the brain of the platyfish (Xiphophorus maculatus) as determined by immunocytochemistry. Cell Tissue Res. 229: 75-84. KALLMAN, K. D., 1970 Sex determination and the restriction of pigment patterns to the X and Y chromosomes in the populations of the poeciliid fish, Xiphophorusmaculatus, from the Belize and Sibun Rivers of British Honduras. Zoologica 55: 116. KALLMAN, K. D., 1975 The platyfish, Xiphophorusmaculatus, pp. 81-132 in Handbook of Genetics, Vol. 4, edited by R. C. KING. Plenum Press, New York. KALLMAN, K. D., 1984 A newlook at sex determination in the
Poeciliid fishes, pp. 95- 171, in Evolutionary Genetics of Fishes, edited by B. J. TURNER. Plenum Press, New York. KALLMAN, K. D., 1989 Genetic control of size at maturity in Xiphophorus, pp. 163-184, in Ecology and Evolution of Liuebearing Fishes (Poeciliidae), edited by G. K. MEFFE and F. S. SNELSON. Prentice-Hall, Englewood Cliffs, N.J. KALLMAN, K. D., and R.BORKOSKI, 1978 A sex-linked gene controlling the onset of sexual maturity in female and male platyfish (Xifhophorusmaculatus), fecundity in females and adult size in males. Genetics 8 9 79-1 19. KALLMAN, K. D., and M. P. SCHREIBMAN, 1973 A sex-linked gene controlling gonadotrop differentiation and its significance in determining the age of sexual maturation and size of platyfish, Xiphophorus maculatus. Gen. Comp. Endocrinol. 21: 287-304. KALLMAN, K. D., M. P. SCHREIBMAN and V. BORKOSKI, 1973 Genetic control of gonadotrop differentiation in the platyfish, Xifhophorusmaculatus (Poeciliidae). Science 181: 678-680. MORIZOT, D. C., 1989 Linkage maps of biochemical loci in nonsalmonid fishes, in Genetic Maps 1989: A Compilation of Linkage and Restriction Maps of Genetically Studied Organisms, Vol. 5 , edited by S. J. O’Brien. Cold Spring Harbor Laboratories, Cold Spring Harbor, N.Y. MORIZOT,D. C., S. A. SLAUGENHAUPT, K. D. KALLMANand A. CHAKRAVARTI, 1991 Genetic linkage map offishes of the genus Xiphophorus (Teleostei: Poeciliidae). Genetics 127: 399410. NELSON, K. G., T. TAKAHASHI, N. L. BOSSERT,D. K. WALMER and J. A. MCLACHLAN, 1991 Epidermal growth factors replaces estrogen in the stimulation of female genital-tract growth and differentiation. Proc. Natl. Acad. Sci. USA 88: 21-25. SCHARTL, M., 1990 Homology of the melanoma-inducing loci in the genus Xiphophorus. Genetics 126: 1083-1091. ULLRICH,A., and J. SCHLESSINGER, 1990 Signal transduction by receptors with tyrosine kinase activity. Cell 61: 203-21 2. WITTBRODT, J., D. ADAM,B. MALITSCHENK,W. MAUELLER, F. RAULF,A. TELLINGS,S. M. ROBERTSON and M. SCHARTL, 1989 The melanoma-induced locus (Tu) of Xiphophorus encodes a novel putative receptor tyrosine kinase. Nature 341: 415-421.
