title: Evolution of circular permutations in multidomain proteins.
abstract: Modular rearrangements play an important role in protein evolution. Functional modules, often tantamount to structural domains or smaller fragments, are in many cases well conserved but reoccur in a different order and across many protein families. The underlying genetic mechanisms are gene duplication, fusion, and loss of sequence fragments. As a consequence, the sequential order of domains can be inverted, leading to what is known as circularly permutated proteins. Using a recently developed algorithm, we have identified a large number of such rearrangements and analyzed their evolutionary history. We searched for examples which have arisen by one of the three postulated mechanisms: independent fusion/fission, "duplication/deletion," and plasmid-mediated "cut and paste." We conclude that all three mechanisms can be observed, with the independent fusion/fission being the most frequent. This can be partly attributed to highly mobile domains. Duplication/deletion has been found in modular proteins such as peptide synthases.
authors.affiliation: Division of Bioinformatics, School of Biological Sciences, University of Münster, Schlossplatz 4, Münster, Germany. january@uni-muenster.de
authors.forename: January
authors.initials: J
authors.lastname: Weiner
authors.forename: Erich
authors.initials: E
authors.lastname: Bornberg-Bauer
mesh_terms: D001105:Archaea / Q000235:genetics; D001419:Bacteria / Q000235:genetics; D001665:Binding Sites; D004270:DNA, Circular / Q000235:genetics; D030562:Databases, Protein; D019143:Evolution, Molecular; D005810:Multigene Family; D017434:Protein Structure, Tertiary / Q000235:genetics*; D011506:Proteins / Q000235:genetics*
chemical_list: D004270:DNA, Circular; D011506:Proteins