title: Protein expansion is primarily due to indels in intrinsically disordered regions.
abstract: 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 and fast-evolving proteins is hampered by the difficulty involved in correctly aligning such sequences. Here, we circumvent this problem by first only analyzing homologous proteins based on length variation rather than pairwise alignments. Using this approach, we find a surprisingly strong relationship between difference in length and difference in the number of intrinsically disordered residues, where up to three quarters of the length variation can be explained by changes in the number of intrinsically disordered residues. Further, we find that disorder is common in both insertions and deletions. 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 lowered selective pressure for indels to occur within intrinsically disordered regions.
authors.affiliation: Science for Life Laboratory, Bioinformatics Infrastructure for Life Sciences, Department of Biochemistry and Biophysics, Stockholm University, Solna, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Light
authors.forename: Rauan
authors.initials: R
authors.lastname: Sagit
authors.forename: Oxana
authors.initials: O
authors.lastname: Sachenkova
authors.forename: Diana
authors.initials: D
authors.lastname: Ekman
authors.forename: Arne
authors.initials: A
authors.lastname: Elofsson
mesh_terms: D000595:Amino Acid Sequence; D019143:Evolution, Molecular; D014644:Genetic Variation; D054643:INDEL Mutation; D064267:Intrinsically Disordered Proteins / Q000737:chemistry* / Q000235:genetics*; D008958:Models, Molecular; D010802:Phylogeny; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D064267:Intrinsically Disordered Proteins; D011506:Proteins
keywords: disordered proteins; indels; insertions and deletions; protein evolution; protein structure