Department of Molecular Genetics and Microbiology, University of Florida, College of Medicine, 1660 SW Archer Road, Gainesville, FL 32610, USA.
BMC Evol Biol. 2010 Mar 1;10:64. doi: 10.1186/1471-2148-10-64.
Chaperonin proteins are well known for the critical role they play in protein folding and in disease. However, the recent identification of three diverged chaperonin paralogs associated with the human Bardet-Biedl and McKusick-Kaufman Syndromes (BBS and MKKS, respectively) indicates that the eukaryotic chaperonin-gene family is larger and more differentiated than previously thought. The availability of complete genome sequences makes possible a definitive characterization of the complete set of chaperonin sequences in human and other species.
We identified fifty-four chaperonin-like sequences in the human genome and similar numbers in the genomes of the model organisms mouse and rat. In mammal genomes we identified, besides the well-known CCT chaperonin genes and the three genes associated with the MKKS and BBS pathological conditions, a newly-defined class of chaperonin genes named CCT8L, represented in human by the two sequences CCT8L1 and CCT8L2. Comparative analyses from several vertebrate genomes established the monophyletic origin of chaperonin-like MKKS and BBS genes from the CCT8 lineage. The CCT8L gene originated from a later duplication also in the CCT8 lineage at the onset of mammal evolution and duplicated in primate genomes. The functionality of CCT8L genes in different species was confirmed by evolutionary analyses and in human by expression data. Detailed sequence analysis and structural predictions of MKKS, BBS and CCT8L proteins strongly suggested that they conserve a typical chaperonin-like core structure but that they are unlikely to form a CCT-like oligomeric complex. The characterization of many newly-discovered chaperonin pseudogenes uncovered the intense duplication activity of eukaryotic chaperonin genes.
In vertebrates, chaperonin genes, driven by intense duplication processes, have diversified into multiple classes and functionalities that extend beyond their well-known protein-folding role as part of the typical oligomeric chaperonin complex, emphasizing previous observations on the involvement of individual CCT monomers in microtubule elongation. The functional characterization of newly identified chaperonin genes will be a challenge for future experimental analyses.
伴侣蛋白以其在蛋白质折叠和疾病中的关键作用而闻名。然而，最近发现与人类 Bardet-Biedl 和 McKusick-Kaufman 综合征（分别为 BBS 和 MKKS）相关的三种分化的伴侣蛋白 paralogs，表明真核伴侣蛋白基因家族比以前想象的更大、更分化。完整基因组序列的可用性使得有可能对人类和其他物种中完整的伴侣蛋白序列进行明确的特征描述。
我们在人类基因组中鉴定了 54 个伴侣蛋白样序列，在模式生物小鼠和大鼠的基因组中也鉴定了类似数量的序列。在哺乳动物基因组中，除了众所周知的 CCT 伴侣蛋白基因和与 MKKS 和 BBS 病理条件相关的三个基因外，我们还鉴定了一类新定义的伴侣蛋白基因，命名为 CCT8L，在人类中由两个序列 CCT8L1 和 CCT8L2 代表。来自几个脊椎动物基因组的比较分析确立了与 MKKS 和 BBS 基因从 CCT8 谱系中单系起源的伴侣蛋白样基因。CCT8L 基因起源于哺乳动物进化开始时 CCT8 谱系中的一个后期复制，并且在灵长类基因组中复制。对不同物种的进化分析和人类的表达数据证实了 CCT8L 基因的功能。对 MKKS、BBS 和 CCT8L 蛋白的详细序列分析和结构预测强烈表明，它们保守了典型的伴侣蛋白样核心结构，但它们不太可能形成 CCT 样寡聚复合物。对许多新发现的伴侣蛋白假基因的特征描述揭示了真核伴侣蛋白基因的强烈复制活性。
在脊椎动物中，伴侣蛋白基因受到强烈复制过程的驱动，已经多样化为多个类和功能，超出了它们作为典型寡聚伴侣蛋白复合物的蛋白质折叠作用，这强调了以前关于单个 CCT 单体参与微管伸长的观察结果。对新鉴定的伴侣蛋白基因的功能特征描述将是未来实验分析的一个挑战。
