The Xiphophorus Genetic Stock Center, Texas State University, San Marcos, TX 78666;
The Xiphophorus Genetic Stock Center, Texas State University, San Marcos, TX 78666.
Proc Natl Acad Sci U S A. 2020 Nov 24;117(47):29786-29794. doi: 10.1073/pnas.2010133117. Epub 2020 Nov 9.
Mixing genomes of different species by hybridization can disrupt species-specific genetic interactions that were adapted and fixed within each species population. Such disruption can predispose the hybrids to abnormalities and disease that decrease the overall fitness of the hybrids and is therefore named as hybrid incompatibility. Interspecies hybridization between southern platyfish and green swordtails leads to lethal melanocyte tumorigenesis. This occurs in hybrids with tumor incidence following progeny ratio that is consistent with two-locus interaction, suggesting melanoma development is a result of negative epistasis. Such observations make one of the only two vertebrate hybrid incompatibility examples in which interacting genes have been identified. One of the two interacting loci has been characterized as a mutant epidermal growth factor receptor. However, the other locus has not been identified despite over five decades of active research. Here we report the localization of the melanoma regulatory locus to a single gene, , which shows all expected features of the long-sought oncogene interacting locus. Our findings provide insights into the role of regulation in regard to cancer etiology. Finally, they provide a molecular explainable example of hybrid incompatibility.
通过杂交混合不同物种的基因组会破坏每个物种群体中适应和固定的物种特异性遗传相互作用。这种破坏会使杂种易患异常和疾病，从而降低杂种的整体适应性，因此被称为杂种不亲和性。南方鲈和绿剑尾鱼之间的种间杂交会导致致命的黑色素瘤肿瘤发生。这种情况发生在具有肿瘤发病率的杂种中，其后代比例与双基因座相互作用一致，这表明黑色素瘤的发展是负上位性的结果。这些观察结果使这成为仅有的两个已确定相互作用基因的脊椎动物杂种不亲和性实例之一。两个相互作用的基因座之一已被表征为突变的表皮生长因子受体。然而，尽管经过五十多年的积极研究，另一个基因座仍未被确定。在这里，我们将黑色素瘤调节基因座定位到一个基因上，该基因显示出长期寻求的致癌基因相互作用基因座的所有预期特征。我们的发现为癌症病因学中 调节的作用提供了深入了解。最后，它们为杂种不亲和性提供了一个可解释的分子实例。
