title: The relationship between domain duplication and recombination.
abstract: Protein domains represent the basic evolutionary units that form proteins. Domain duplication and shuffling by recombination are probably the most important forces driving protein evolution and hence the complexity of the proteome. While the duplication of whole genes as well as domain-encoding exons increases the abundance of domains in the proteome, domain shuffling increases versatility, i.e. the number of distinct contexts in which a domain can occur. Here, we describe a comprehensive, genome-wide analysis of the relationship between these two processes. We observe a strong and robust correlation between domain versatility and abundance: domains that occur more often also have many different combination partners. This supports the view that domain recombination occurs in a random way. However, we do not observe all the different combinations that are expected from a simple random recombination scenario, and this is due to frequent duplication of specific domain combinations. When we simulate the evolution of the protein repertoire considering stochastic recombination of domains followed by extensive duplication of the combinations, we approximate the observed data well. Our analyses are consistent with a stochastic process that governs domain recombination and thus protein divergence with respect to domains within a polypeptide chain. At the same time, they support a scenario in which domain combinations are formed only once during the evolution of the protein repertoire, and are then duplicated to various extents. The extent of duplication of different combinations varies widely and, in nature, will depend on selection for the domain combination based on its function. Some of the pair-wise domain combinations that are highly duplicated also recur frequently with other partner domains, and thus represent evolutionary units larger than single protein domains, which we term "supra-domains".
authors.affiliation: MRC Laboratory of Molecular Biology, Hills Rd, Cambridge CB2 2QH, UK. cvogel@mrc-lmb.cam.ac.uk
authors.forename: Christine
authors.initials: C
authors.lastname: Vogel
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Teichmann
authors.forename: Jose
authors.initials: J
authors.lastname: Pereira-Leal
mesh_terms: D000818:Animals; D019143:Evolution, Molecular; D020440:Gene Duplication; D023281:Genomics; D006801:Humans; D008957:Models, Genetic; D017434:Protein Structure, Tertiary / Q000235:genetics; D011506:Proteins / Q000737:chemistry* / Q000235:genetics*; D011995:Recombination, Genetic / Q000235:genetics*
chemical_list: D011506:Proteins