Modular evolution of domain repeat proteinsmetal-binding and domain repeats of metallothioneins in mollusks and chordates

Resumen

Proteins are composed of domains, a well-defined region within a protein that constitutes a stable, independently folding, compact structural unit, and that usually performs a specific function. During protein evolution, domains have been used as a ‘modules’, and the vast majority of the current proteins show a modular organization in which two or more domains are combined. While the creation of multi-domain proteins through shuffling different domains has been studied extensively, the evolution of proteins made of tandem repeats of a same domain has been less investigated. It is known, for instance, that the fraction of proteins with domain repeats is higher in multicellular organisms than in unicellular organisms, or that proteins with domain repeats seem to be related with stress response functions or with the acquisition of high yielding capacity, but the origin, the genetic mechanisms and the evolutionary forces controlling the expansion of domains repeats in modular proteins are still poorly understood. To investigate the functional and structural evolution of modular proteins with domain repeats, we have chosen the Metallothioneins (MTs) as a case study. MTs are present across all the tree of life and due to their metal-binding ability have been involved in metal homeostasis and detoxification of many organisms. They are modular cysteinerich proteins that bind metal ions through functionally and structurally independent domains that form metal-thiolate clusters. Many MTs are bi-modular proteins made of a tandem repetition of two similar (although not identical) metal-binding domains. There also are large multi-modular MTs that have expanded the number of their domain repeats, and therefore, their metal-binding capacity. Studying the evolution of metallothionein domains in several phyla can help us to understand, at some level, the evolvability of organisms to adapt to new environmental conditions. In our studies we have identified, analysed, characterized and compared many MTs from different groups of selected organisms (chordates and molluscs) in order to study their domain composition and arrangement, and to untangle the evolution of their modular organization.