Another source of difficulties that we have experienced, as mentioned above, is uncertainties in protein alignments due to duplication of domains in some family members.
The conserved domain search tool (CD) was used to predict duplication of domains within the analyzed data set, as compared against the conserved domain database (CDD) (Marchler-Bauer and Bryant 2004; Marchler-Bauer et al. 2009).
Domain shuffling, which refers to the duplication of a domain or the insertion of a domain from one gene into another, may be an important contributor to phenotypic complexity.
The duplication of a domain induces divergence of the duplicate domain through mutations, insertions or deletions, producing modified structures and functions that distinguish it from its ancestor, but in our methodology it is only identified if it retains detectable structural similarity.
Bjorklund et al. (2005) calculated the differences of domain architectures between homologous proteins and observed that the evolution of most multidomain proteins could be explained by stepwise insertions of single domains and tandem duplications of domains.
A common theme for these families is the duplication of a domain followed by the divergence of the specificity of the resulting domains.
The core domain of COG1517 is ~150 aa; several proteins, e.g. TM1812, contain a duplication of this domain, and several fusions, in addition to the one with HTH, were detected.
Both processes lead to the deletion or duplication of a domain.
The second event of duplication was observed in genes harboring multiple copies of LysM, providing evidence of recent intergene duplication of this domain within paralogues.
However, PoptrIAA7.1 was found to be unique in that it contains a tandem duplication of the domain II region (See Additional file 5).
