Marín Ignacio
Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Científicas, Calle Jaime Roig 11, Valencia 46010, Spain.
J Mol Evol. 2008 Jul;67(1):41-50. doi: 10.1007/s00239-008-9122-4. Epub 2008 Jun 4.
Dominant mutations in the LRRK2 gene, a member of the Roco family, cause both familial and sporadic Parkinson disease. LRRK genes had so far been detected only in bilaterian animals. In deuterostomes, including humans, two LRRK genes (LRRK1 and LRRK2) exist, while in protostomes a single LRRK gene has been found. In this study, I combine structural and phylogenetic analyses to show that the cnidarian Nematostella vectensis has four LRRK genes. One of them is a bona fide orthologue of the human LRRK2 gene, demonstrating that this gene has an ancient origin. Two others are, respectively, orthologues of the deuterostome LRRK1 and the protostome LRRK genes. The fourth gene is probably cnidarian-specific. This precise characterization of the early evolution of LRRK genes in animals has important implications, because it indicates that the Drosophila and Caenorhabditis LRRK genes, which are studied to gain an understanding of LRRK2 function, are not true orthologues of the human Parkinson disease gene. Novel functional insights are also gained by comparison of the structures of LRRK2 genes in distantly related species.
LRRK2基因是Roco家族的成员之一，其显性突变会导致家族性和散发性帕金森病。到目前为止，LRRK基因仅在两侧对称动物中被检测到。在包括人类在内的后口动物中，存在两个LRRK基因（LRRK1和LRRK2），而在原口动物中仅发现了一个LRRK基因。在本研究中，我结合结构和系统发育分析表明，刺胞动物星状海葵有四个LRRK基因。其中一个是人类LRRK2基因的真正直系同源基因，这表明该基因起源古老。另外两个分别是后口动物LRRK1和原口动物LRRK基因的直系同源基因。第四个基因可能是刺胞动物特有的。对动物中LRRK基因早期进化的这种精确表征具有重要意义，因为这表明为了解LRRK2功能而进行研究的果蝇和秀丽隐杆线虫的LRRK基因并非人类帕金森病基因的真正直系同源基因。通过比较远缘物种中LRRK2基因的结构，也获得了新的功能见解。
