Evolution domain duplication

Anyhow, globular proteins are commonly built by the assembly of globular domains. It is a plausible assumption, although very difficult to prove, that at the early stage of protein evolution, domains were independent molecules endowed with specific functional properties. Later, after the different events of gene duplication or fusion, they appeared as compact building blocks of... 

The sequencing of a- and /3-spectrin, a-actinin, and dystrophin has revealed similarities not only within the spectrin repeat, but also the other domains and motifs present within these proteins. Subsequent analyses have revealed an evolutionary pathway for the divergence of spectrin and dystrophin from a common a-actinin ancestor via a series of rearrangements, duplications, and evolution of repeats and other domains, as well as the acquisition of unique domains such as PH, WW, and SHS (Fig. 2). 

The following sections explore nature s use of domain swapping to evolve new function. These include the formation of multifunctional proteins, tandem duplication, domain recruitment, and cicular permutation (Fig. 1). The evolution of several enzymes in the purine (Fig. 2) and pyrimidine (Fig. 3) de novo biosynthetic pathways, as well as other enzymes, are discussed as illustrative examples. 

The pronounced threefold repeat in the six-domain molecule ceruloplasmin contradicts evolution by a duplication of an ascorbate oxidaselike molecule and suggests evolution from the tandem two-domain molecule by triplication, possibly before acquisition of the trinuclear copper site. This might have occurred later, between the N- and C-terminal domains. 

This reaction takes place in a second ATP-grasp domain within the enzyme. The active sites leading to carbamic acid formation and carbamoyl phosphate formation are very similar, revealing that this enzyme evolved by a gene duplication event. Indeed, duplication of a gene encoding an ATP-grasp domain followed by specialization was central to the evolution of nucleotide biosynthetic processes (Section 25.2.3). 

---