This article is part of the supplement: Ninth International Conference on Bioinformatics (InCoB2010): Bioinformatics
Intrinsically disordered domains deviate significantly from random sequences in mammalian proteins
- Equal contributors
1 Laboratory of Host Defense, WPI Immunology Frontier Research Center (IFReC), Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan
2 Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokane-dai, Minato-ku, Tokyo 108-8639, Japan
3 Laboratory of Systems Immunology, WPI Immunology Frontier Research Center (IFReC), Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan
BMC Bioinformatics 2010, 11(Suppl 7):S7 doi:10.1186/1471-2105-11-S7-S7Published: 15 October 2010
In order to characterize mammalian intrinsically disordered domains (IDDs) we examined the patterns in their amino acid abundance as well as overrepresented local sequence motifs. We considered IDDs from mouse proteins associated with innate immune responses as well as a set of generic human genes. These sets were compared with artificially generated random sequences with the same overall amino acid abundance and length distributions. IDDs were then clustered by amino acid abundance, and further analyzed in terms of co-occurrence of clusters with functionally characterized Pfam domains.
Overall, IDDs were very different from randomly generated sequences. The deviation from random distributions was at least as great as that for ordered domains, for which the deviation can be rationalized in terms of strong evolutionary pressure for structure and function. The co-occurrence of certain Pfam domains with specific IDD clusters was found to be significant (p-value < 0.01). Local sequence motifs that were over-represented in the innate immune set consisted mostly of low complexity fragments, primarily characterized by amino acid repeats, and could not be assigned an obvious functional role.
Our results suggest that IDDs are constrained within a narrow subset of possible sequences. This is most likely a result of biophysical restraints that have yet to be elucidated. More detailed examination of the functional relationship between the IDDs and associated Pfam domains is one possible avenue of investigation.