Caetano-Anollés Gustavo, Yafremava Liudmila S, Gee Hannah, Caetano-Anollés Derek, Kim Hee Shin, Mittenthal Jay E
Department of Crop Sciences, University of Illinois, Urbana, IL 61801, United States.
Int J Biochem Cell Biol. 2009 Feb;41(2):285-97. doi: 10.1016/j.biocel.2008.08.022. Epub 2008 Aug 26.
One fundamental goal of current research is to understand how complex biomolecular networks took the form that we observe today. Cellular metabolism is probably one of the most ancient biological networks and constitutes a good model system for the study of network evolution. While many evolutionary models have been proposed, a substantial body of work suggests metabolic pathways evolve fundamentally by recruitment, in which enzymes are drawn from close or distant regions of the network to perform novel chemistries or use different substrates. Here we review how structural and functional genomics has impacted our knowledge of evolution of modern metabolism and describe some approaches that merge evolutionary and structural genomics with advances in bioinformatics. These include mining the data on structure and function of enzymes for salient patterns of enzyme recruitment. Initial studies suggest modern metabolism originated in enzymes of nucleotide metabolism harboring the P-loop hydrolase fold, probably in pathways linked to the purine metabolic subnetwork. This gateway of recruitment gave rise to pathways related to the synthesis of nucleotides and cofactors for an ancient RNA world. Once the TIM beta/alpha-barrel fold architecture was discovered, it appears metabolic activities were recruited explosively giving rise to subnetworks related to carbohydrate and then amino acid metabolism. Remarkably, recruitment occurred in a layered system reminiscent of Morowitz's prebiotic shells, supporting the notion that modern metabolism represents a palimpsest of ancient metabolic chemistries.
当前研究的一个基本目标是了解复杂的生物分子网络是如何形成我们如今所观察到的形式的。细胞代谢可能是最古老的生物网络之一，并且构成了一个用于研究网络进化的良好模型系统。尽管已经提出了许多进化模型，但大量工作表明代谢途径基本上是通过招募进化而来的，即酶从网络的近邻或遥远区域被吸引过来，以执行新的化学反应或使用不同的底物。在这里，我们回顾结构和功能基因组学如何影响了我们对现代代谢进化的认识，并描述了一些将进化与结构基因组学与生物信息学进展相结合的方法。这些方法包括挖掘酶的结构和功能数据，以寻找酶招募的显著模式。初步研究表明，现代代谢起源于具有P环水解酶折叠的核苷酸代谢酶，可能存在于与嘌呤代谢子网相关的途径中。这种招募途径产生了与古代RNA世界的核苷酸和辅因子合成相关的途径。一旦发现了TIMβ/α桶状折叠结构，代谢活动似乎就会爆发式地被招募，从而产生与碳水化合物以及随后的氨基酸代谢相关的子网。值得注意的是，招募发生在一个类似于莫罗维茨的益生元壳层的分层系统中，这支持了现代代谢代表古代代谢化学的重写本这一观点。
