Protein expansion is primarily due to indels in intrinsically disordered regions
(English)Manuscript (preprint) (Other academic)
Proteins evolve not only through point mutations but also by insertion and deletion events, which affect the length of the protein. It is well known that such indel events most frequently occur in surface exposed loops. However, detailed analysis of indel events in distantly related proteins is hampered by the difficulty involved in correctly aligning such sequences. Here, we circumvent this problem by analyzing homologous proteins based on length variation rather than pairwise alignments. We find a surprisingly strong relationship between difference in length and difference in the number of intrinsically disordered residues, where more than half of the length variation can be explained by changes in the number of intrinsically disordered residues. A more detailed analysis reveals that indel events do not induce disorder but rather that already disordered regions accrue indels, suggesting that there is a significantly lowered selective pressure for indels to occur within intrinsically disordered regions.
Bioinformatics and Systems Biology
Research subject Biochemistry
IdentifiersURN: urn:nbn:se:su:diva-88551OAI: oai:DiVA.org:su-88551DiVA: diva2:612037
ProjectsGeneFun project, contract No: LSHG-CT-2004-503567EDICT project, contract No: FP7-HEALTH-F4-2007-201924
FunderSwedish Research Council, VRNT 2009-5072Swedish Research Council, VR-M 2010-3555Swedish Research Council, VR-NT 2012-5046EU, FP7, Seventh Framework Programme, 201924