Assessing Conservation of Disordered Regions in Proteins

Intrinsically disordered regions (IDRs) are highly populated in eukaryotic proteomes and serve pivotal, mostly regulatory functions. Many IDRs appear to be functionally conserved and analysis of protein domains indicates high propensity of conserved regions predicted to be disordered. Nevertheless, it is difficult to assess conservation of IDRs in general due to their fast evolution and low sequence similarity. We propose three measures to evaluate conservation of IDRs: i) similarities of the disorder profiles using different prediction conditions; ii) the conservation of amino acids with propensities for promoting either disorder or order; and iii) the overlap between disordered/ordered regions. These measures are computed on multiple sequence alignments that also include low-complexity regions of proteins. Using three subunits of the Mediator complex of transcription regulation from Homo sapiens and Drosophila melanogaster as an example we show that despite of their sequence dissimilarity IDRs can be conserved and likely carry out the same function in different organisms.