Evolution based on domain combinations: the case of glutaredoxins

In this work we analyze the distribution and evolution of GRX proteins in archaea, bacteria and eukaryotes. We study over one thousand GRX proteins, each containing at least one GRX domain, from hundreds of different organisms and trace the origin and evolution of the GRX domain within the tree of life.Our results suggest that single domain GRX proteins of the CGFS and CPYC classes have, each, evolved through duplication and divergence from one initial gene that was present in the last common ancestor of all organisms. Remarkably, we identify a case of convergent evolution in domain architecture that involves the GRX domain. Two independent recombination events of a TRX domain to a GRX domain are likely to have occurred, which is an exception to the dominant mechanism of domain architecture evolution.Domain duplication and shuffling by recombination and fusion, followed by divergence are the more frequent mechanisms for the evolution of proteins [1]. It has been estimated that such recombination and fusion events are likely to occur only once for a given multidomain architecture and that, after such an event, the fusion protein is duplicated and/or diverges over time [1]. In addition, statistical analysis of known multidomain proteins has shown that a) there is a strong bias for individual domains involved in recombination and fusion events to be short [2], and b) some specific sets of recombined domains (supra domains) participate in further recombination and fusion events [3]. This provides a model for the dominant mode of domain architecture evolution in proteins that is very much consensual. Recent work has further estimated that between 88% and 95% of all multidomain architectures have evolved through such mechanisms [4-6]. The remaining architectures are likely to have evolved through convergent evolution [6]. A recent theory proposes that, during major evolutionary transitions, evolution is biphasic, further complicating the model of protein evolution [7]. Ac