Graef I A, Gastier J M, Francke U, Crabtree G R
Department of Genetics, Howard Hughes Medical Institute, Stanford University Medical School, Stanford, CA 94305-5323, USA.
Proc Natl Acad Sci U S A. 2001 May 8;98(10):5740-5. doi: 10.1073/pnas.101602398.
The recent sequencing of several complete genomes has made it possible to track the evolution of large gene families by their genomic structure. Following the large-scale association of exons encoding domains with well defined functions in invertebrates could be useful in predicting the function of complex multidomain proteins in mammals produced by accretion of domains. With this objective, we have determined the genomic structure of the 14 genes in invertebrates and vertebrates that contain rel domains. The sequence encoding the rel domain is defined by intronic boundaries and has been recombined with at least three structurally and functionally distinct genomic sequences to generate coding sequences for: (i) the rel/Dorsal/NFkappaB proteins that are retained in the cytoplasm by IkB-like proteins; (ii) the NFATc proteins that sense calcium signals and undergo cytoplasmic-to-nuclear translocation in response to dephosphorylation by calcineurin; and (iii) the TonEBP tonicity-responsive proteins. Remarkably, a single exon in each NFATc family member encodes the entire Ca(2+)/calcineurin sensing region, including nuclear import/export, calcineurin-binding, and substrate regions. The Rel/Dorsal proteins and the TonEBP proteins are present in Drosophila but not Caenorhabditis elegans. On the other hand, the calcium-responsive NFATc proteins are present only in vertebrates, suggesting that the NFATc family is dedicated to functions specific to vertebrates such as a recombinational immune response, cardiovascular development, and vertebrate-specific aspects of the development and function of the nervous system.
最近对几个完整基因组的测序使得通过基因组结构追踪大基因家族的进化成为可能。在无脊椎动物中，将编码具有明确功能结构域的外显子进行大规模关联，可能有助于预测通过结构域积累产生的哺乳动物复杂多结构域蛋白的功能。出于这一目的，我们确定了无脊椎动物和脊椎动物中14个含有rel结构域的基因的基因组结构。编码rel结构域的序列由内含子边界定义，并已与至少三个结构和功能不同的基因组序列重组，以产生以下编码序列：(i) 通过类IkB蛋白保留在细胞质中的rel/Dorsal/NFkappaB蛋白；(ii) 感知钙信号并响应钙调神经磷酸酶去磷酸化而发生细胞质到细胞核转运的NFATc蛋白；以及(iii) TonEBP渗透压响应蛋白。值得注意的是，每个NFATc家族成员中的单个外显子编码整个Ca(2+)/钙调神经磷酸酶感应区域，包括核输入/输出、钙调神经磷酸酶结合和底物区域。Rel/Dorsal蛋白和TonEBP蛋白存在于果蝇中，但不存在于秀丽隐杆线虫中。另一方面，钙响应性NFATc蛋白仅存在于脊椎动物中，这表明NFATc家族专门负责脊椎动物特有的功能，如重组免疫反应、心血管发育以及神经系统发育和功能的脊椎动物特有的方面。
