Grandien K, Sommer R J
Max-Planck Institut für Entwicklungsbiologie, Abteilung Evolutionsbiologie, D-72076 Tübingen, Germany.
Genes Dev. 2001 Aug 15;15(16):2161-72. doi: 10.1101/gad.200601.
Hox transcription factors have been implicated in playing a central role in the evolution of animal morphology. Many studies indicate the evolutionary importance of regulatory changes in Hox genes, but little is known about the role of functional changes in Hox proteins. In the nematodes Pristionchus pacificus and Caenorhabditis elegans, developmental processes can be compared at the cellular, genetic, and molecular levels and differences in gene function can be identified. The Hox gene lin-39 is involved in the regulation of nematode vulva development. Comparison of known lin-39 mutations in P. pacificus and C. elegans revealed both conservation and changes of gene function. Here, we study evolutionary changes of lin-39 function using hybrid transgenes and site-directed mutagenesis in an in vivo assay using C. elegans lin-39 mutants. Our data show that despite the functional differences of LIN-39 between the two species, Ppa-LIN-39, when driven by Cel-lin-39 regulatory elements, can functionally replace Cel-lin-39. Furthermore, we show that the MAPK docking and phosphorylation motifs unique for Cel-LIN-39 are dispensable for Cel-lin-39 function. Therefore, the evolution of lin-39 function is driven by changes in regulatory elements rather than changes in the protein itself.
Hox转录因子在动物形态进化中被认为起着核心作用。许多研究表明Hox基因调控变化在进化上的重要性，但对于Hox蛋白功能变化的作用却知之甚少。在太平洋前口动物线虫和秀丽隐杆线虫中，可以在细胞、遗传和分子水平上比较发育过程，并鉴定基因功能的差异。Hox基因lin-39参与线虫阴门发育的调控。对太平洋前口动物线虫和秀丽隐杆线虫中已知的lin-39突变进行比较，揭示了基因功能的保守性和变化。在这里，我们在秀丽隐杆线虫lin-39突变体的体内试验中，使用杂交转基因和定点诱变研究lin-39功能的进化变化。我们的数据表明，尽管两种线虫中LIN-39的功能存在差异，但当由秀丽隐杆线虫lin-39调控元件驱动时，太平洋前口动物线虫的Ppa-LIN-39可以在功能上替代秀丽隐杆线虫的Cel-LIN-39。此外，我们表明，秀丽隐杆线虫Cel-LIN-39特有的MAPK对接和磷酸化基序对于秀丽隐杆线虫Cel-lin-39的功能是可有可无的。因此，lin-39功能的进化是由调控元件的变化而非蛋白质本身的变化驱动的。
