Rosso Lia, Marques Ana Claudia, Weier Manuela, Lambert Nelle, Lambot Marie-Alexandra, Vanderhaeghen Pierre, Kaessmann Henrik
Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
PLoS Biol. 2008 Jun 10;6(6):e140. doi: 10.1371/journal.pbio.0060140.
Gene duplication was prevalent during hominoid evolution, yet little is known about the functional fate of new ape gene copies. We characterized the CDC14B cell cycle gene and the functional evolution of its hominoid-specific daughter gene, CDC14Bretro. We found that CDC14B encodes four different splice isoforms that show different subcellular localizations (nucleus or microtubule-associated) and functional properties. A microtubular CDC14B variant spawned CDC14Bretro through retroposition in the hominoid ancestor 18-25 million years ago (Mya). CDC14Bretro evolved brain-/testis-specific expression after the duplication event and experienced a short period of intense positive selection in the African ape ancestor 7-12 Mya. Using resurrected ancestral protein variants, we demonstrate that by virtue of amino acid substitutions in distinct protein regions during this time, the subcellular localization of CDC14Bretro progressively shifted from the association with microtubules (stabilizing them) to an association with the endoplasmic reticulum. CDC14Bretro evolution represents a paradigm example of rapid, selectively driven subcellular relocalization, thus revealing a novel mode for the emergence of new gene function.
基因复制在类人猿进化过程中很普遍，但我们对新的猿类基因拷贝的功能命运却知之甚少。我们对细胞周期基因CDC14B及其类人猿特异性子代基因CDC14Bretro的功能进化进行了表征。我们发现，CDC14B编码四种不同的剪接异构体，它们表现出不同的亚细胞定位（细胞核或微管相关）和功能特性。一种微管CDC14B变体在1800万至2500万年前（Mya）的类人猿祖先中通过逆转座产生了CDC14Bretro。CDC14Bretro在复制事件后进化出大脑/睾丸特异性表达，并在700万至1200万年前的非洲猿祖先中经历了一段短暂的强烈正选择期。通过复活的祖先蛋白变体，我们证明，在此期间，由于不同蛋白区域的氨基酸替换，CDC14Bretro的亚细胞定位逐渐从与微管的结合（使微管稳定）转变为与内质网的结合。CDC14Bretro的进化代表了快速的、由选择驱动的亚细胞重新定位的一个典型例子，从而揭示了新基因功能出现的一种新模式。
