Computational Biology Unit, Uni Research, University of Bergen, N-5008 Bergen, Norway.
BMC Evol Biol. 2012 May 30;12:75. doi: 10.1186/1471-2148-12-75.
Despite recent progress in studies of the evolution of protein function, the questions what were the first functional protein domains and what were their basic building blocks remain unresolved. Previously, we introduced the concept of elementary functional loops (EFLs), which are the functional units of enzymes that provide elementary reactions in biochemical transformations. They are presumably descendants of primordial catalytic peptides.
We analyzed distant evolutionary connections between protein functions in Archaea based on the EFLs comprising them. We show examples of the involvement of EFLs in new functional domains, as well as reutilization of EFLs and functional domains in building multidomain structures and protein complexes.
Our analysis of the archaeal superkingdom yields the dominating mechanisms in different periods of protein evolution, which resulted in several levels of the organization of biochemical function. First, functional domains emerged as combinations of prebiotic peptides with the very basic functions, such as nucleotide/phosphate and metal cofactor binding. Second, domain recombination brought to the evolutionary scene the multidomain proteins and complexes. Later, reutilization and de novo design of functional domains and elementary functional loops complemented evolution of protein function.
尽管在蛋白质功能进化的研究方面取得了一些进展，但第一个功能蛋白结构域是什么以及它们的基本组成部分是什么，这些问题仍未得到解决。此前，我们提出了基本功能环（EFL）的概念，它是提供生化转化中基本反应的酶的功能单元。它们可能是原始催化肽的后代。
我们基于包含它们的 EFL 分析了古菌中蛋白质功能的遥远进化关系。我们展示了 EFL 参与新功能域的例子，以及 EFL 和功能域在构建多结构域结构和蛋白质复合物中的再利用。
对古菌超界的分析得出了在蛋白质进化的不同时期起主导作用的机制，从而导致了生化功能的几个层次的组织。首先，功能域作为具有基本功能的前生物肽的组合而出现，例如核苷酸/磷酸和金属辅因子结合。其次，结构域重组将多结构域蛋白和复合物引入了进化领域。后来，功能域和基本功能环的再利用和从头设计补充了蛋白质功能的进化。
