title: Coding Regions of Intrinsic Disorder Accommodate Parallel Functions.
abstract: Numerous DNA- and RNA-level functions are embedded in protein-coding regions, which constrains their structure, function, and evolution. Accumulating evidence suggests that such additional, overlapping functions occur preferentially in the coding sequences of intrinsically disordered proteins/regions (IDPs/IDRs), especially in those that are newly incorporated and thus have reduced selective pressure. It is the lack of strict structural constraints that makes disordered proteins more tolerant to mutations and thus more permissive to the appearance of overlapping functions within their coding sequences than structured domains. Therefore, IDPs/IDRs are often mosaics of segments fulfilling protein functionalities and intervening regions primarily carrying nucleotide-level functions. The ensuing complexification of gene-regulatory circuits may have contributed to the evolutionary spread of structural disorder in complex eukaryotic organisms.
authors.affiliation: Flanders Institute for Biotechnology (VIB), Structural Biology Research Center, Vrije Universiteit Brussel, 1050 Pleinlaan 2, Brussels, Belgium.
authors.forename: Rita
authors.initials: R
authors.lastname: Pancsa
authors.affiliation: Flanders Institute for Biotechnology (VIB), Structural Biology Research Center, Vrije Universiteit Brussel, 1050 Pleinlaan 2, Brussels, Belgium; Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok körútja 2, 1117 Budapest, Hungary. Electronic address: ptompa@vub.ac.be.
authors.forename: Peter
authors.initials: P
authors.lastname: Tompa
mesh_terms: D019143:Evolution, Molecular; D005091:Exons; D015870:Gene Expression; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D064267:Intrinsically Disordered Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D016366:Open Reading Frames; D010963:Plasmodium falciparum / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012641:Selection, Genetic; D013329:Structure-Activity Relationship
chemical_list: D064267:Intrinsically Disordered Proteins; D012333:RNA, Messenger
keywords: exonic regulatory code; intrinsically disordered; intrinsically disordered intervening region; overlapping codes; parallel coding; structural constraint