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.