Volff Jean-Nicolas, Schartl Manfred
Physiologische Chemie I, Biofuture Research Group 'Evolutionary Fish Genomics', Biozentrum, University of Würzburg, Am Hubland, D-97074 Würzburg, Germany.
J Struct Funct Genomics. 2003;3(1-4):139-50.
Fishes possess more genes encoding receptor tyrosine kinases from the epidermal growth factor receptor (EGFR) family than other organisms. Three of the four genes present in higher vertebrates have been duplicated early during the evolution of the ray-finned fish lineage possibly as a consequence of an event of whole genome duplication. In the fish Xiphophorus, a much more recent local event of gene duplication of the egfr co-orthologue egfr-b generated a eighth gene, the Xmrk oncogene. This duplicate acquired within a short time a constitutive activity and a pigment cell-specific overexpression responsible for the induction of melanoma in certain interspecific hybrids. Despite its frequent loss during evolution of the genus Xiphophorus, the maintenance of Xmrk in numerous species and its evolution under purifying selection suggest a so far unknown function under certain natural conditions. One of the known functions of Xmrk in tumor cells is the suppression of differentiation of melanocytes induced by the microphthalmia-associated transcription factor MITF. While only one gene with alternative 5' exons and promoters is present in higher vertebrates, two mitf genes were identified in fish. Subfunctionalization of mitf paralogues by differential degeneration of alternative exons and regulatory sequences led particularly to the formation of a mitf gene specifically expressed in the melanocyte lineage. These observations validate fish as an outstanding model to study the mechanisms and biological consequences of gene and genome duplication but underline the complexity of the fish model and the caution necessary in transferring knowledge from fish to higher vertebrates and vice versa.
与其他生物相比，鱼类拥有更多编码来自表皮生长因子受体（EGFR）家族的受体酪氨酸激酶的基因。硬骨鱼系在进化早期，可能由于一次全基因组复制事件，高等脊椎动物中存在的四个基因中的三个发生了复制。在鱼类剑尾鱼中，egfr同源基因egfr - b更近发生的一次局部基因复制事件产生了第八个基因，即Xmrk癌基因。这个复制基因在短时间内获得了组成型活性和色素细胞特异性过表达，导致某些种间杂交后代诱发黑色素瘤。尽管Xmrk在剑尾鱼属的进化过程中经常丢失，但它在许多物种中得以保留并在纯化选择下进化，这表明在某些自然条件下存在迄今未知的功能。Xmrk在肿瘤细胞中的已知功能之一是抑制小眼相关转录因子MITF诱导的黑素细胞分化。高等脊椎动物中仅存在一个具有可变5'外显子和启动子的基因，而在鱼类中鉴定出了两个mitf基因。通过可变外显子和调控序列的差异退化，mitf旁系同源基因的亚功能化尤其导致了一个在黑素细胞系中特异性表达的mitf基因的形成。这些观察结果证实鱼类是研究基因和基因组复制机制及生物学后果的优秀模型，但也强调了鱼类模型的复杂性以及在将知识从鱼类转移到高等脊椎动物以及反之亦然时所需的谨慎性。
