McNally David, Fares Mario A
Evolutionary Genetics and Bioinformatics Laboratory, Department of Genetics, Smurfit Institute of Genetics, University of Dublin, Trinity College, Dublin, Ireland.
BMC Evol Biol. 2007 May 22;7:81. doi: 10.1186/1471-2148-7-81.
Heat-shock proteins are specialized molecules performing different and essential roles in the cell including protein degradation, folding and trafficking. GroEL is a 60 Kda heat-shock protein ubiquitous in bacteria and has been regarded as an important molecule implicated in chronic inflammatory processes caused by Chlamydiae infections. GroEL in Chlamydiae became duplicated at the origin of the Chlamydiae lineage presenting three distinct molecular chaperones, namely the original protein GroEL1 (Ct110), and its paralogous proteins GroEL2 (Ct604) and GroEL3 (Ct755). These chaperones present differential and independent expressions during the different stages of Chlamydiae infections and have been suggested to present differential physiological and regulatory roles.
In this comprehensive in silico study we show that GroEL protein paralogs have diverged functionally after the different gene duplication events and that this divergence has occurred mainly between GroEL3 and GroEL1. GroEL2 presents an intermediate functional divergence pattern from GroEL1. Our results point to the different protein-protein interaction patterns between GroEL paralogs and known GroEL protein clients supporting their functional divergence after groEL gene duplication. Analysis of selective constraints identifies periods of adaptive evolution after gene duplication that led to the fixation of amino acid replacements in GroEL protein domains involved in the interaction with GroEL protein clients.
We demonstrate that GroEL protein copies in Chlamydiae species have diverged functionally after the gene duplication events. We also show that functional divergence has occurred in important functional regions of these GroEL proteins and that very probably have affected the ancestral GroEL regulatory role and protein-protein interaction patterns with GroEL client proteins. Most of the amino acid replacements that have affected interaction with protein clients and that were responsible for the functional divergence between GroEL paralogs were fixed by adaptive evolution after the groEL gene duplication events.
热休克蛋白是在细胞中发挥不同且重要作用的特殊分子，包括蛋白质降解、折叠和运输。GroEL是一种在细菌中普遍存在的60千道尔顿热休克蛋白，被认为是参与衣原体感染引起的慢性炎症过程的重要分子。衣原体中的GroEL在衣原体谱系起源时发生了复制，产生了三种不同的分子伴侣，即原始蛋白GroEL1（Ct110）及其旁系同源蛋白GroEL2（Ct604）和GroEL3（Ct755）。这些伴侣蛋白在衣原体感染的不同阶段呈现出差异且独立的表达，并被认为具有不同的生理和调节作用。
在这项全面的计算机模拟研究中，我们表明GroEL蛋白旁系同源物在不同的基因复制事件后功能发生了分化，这种分化主要发生在GroEL3和GroEL1之间。GroEL2呈现出与GroEL1中间的功能分化模式。我们的结果表明GroEL旁系同源物与已知的GroEL蛋白客户之间存在不同的蛋白质 - 蛋白质相互作用模式，支持它们在groEL基因复制后的功能分化。对选择限制的分析确定了基因复制后的适应性进化时期，这导致了参与与GroEL蛋白客户相互作用的GroEL蛋白结构域中氨基酸替换的固定。
我们证明衣原体物种中的GroEL蛋白拷贝在基因复制事件后功能发生了分化。我们还表明功能分化发生在这些GroEL蛋白的重要功能区域，并且很可能影响了祖先GroEL的调节作用以及与GroEL客户蛋白的蛋白质 - 蛋白质相互作用模式。大多数影响与蛋白客户相互作用并导致GroEL旁系同源物功能分化的氨基酸替换是在groEL基因复制事件后通过适应性进化固定下来的。
