title: Deciphering the cause of evolutionary variance within intrinsically disordered regions in human proteins.
abstract: Why the intrinsically disordered regions evolve within human proteome has became an interesting question for a decade. Till date, it remains an unsolved yet an intriguing issue to investigate why some of the disordered regions evolve rapidly while the rest are highly conserved across mammalian species. Identifying the key biological factors, responsible for the variation in the conservation rate of different disordered regions within the human proteome, may revisit the above issue. We emphasized that among the other biological features (multifunctionality, gene essentiality, protein connectivity, number of unique domains, gene expression level and expression breadth) considered in our study, the number of unique protein domains acts as a strong determinant that negatively influences the conservation of disordered regions. In this context, we justified that proteins having a fewer types of domains preferably need to conserve their disordered regions to enhance their structural flexibility which in turn will facilitate their molecular interactions. In contrast, the selection pressure acting on the stretches of disordered regions is not so strong in the case of multi-domains proteins. Therefore, we reasoned that the presence of conserved disordered stretches may compensate the functions of multiple domains within a single domain protein. Interestingly, we noticed that the influence of the unique domain number and expression level acts differently on the evolution of disordered regions from that of well-structured ones.
authors.affiliation: a Machine Intelligence Unit , Indian Statistical Institute , 203 Barrackpore Trunk Road, Kolkata 700108 , India.
authors.forename: Sanghita
authors.initials: S
authors.lastname: Banerjee
authors.affiliation: b Department of Biology , University of Nevada , Reno , NV , USA.
authors.forename: Sandip
authors.initials: S
authors.lastname: Chakraborty
authors.affiliation: a Machine Intelligence Unit , Indian Statistical Institute , 203 Barrackpore Trunk Road, Kolkata 700108 , India.
authors.forename: Rajat K
authors.initials: RK
authors.lastname: De
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D030562:Databases, Protein; D019143:Evolution, Molecular; D006801:Humans; D064267:Intrinsically Disordered Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D000072417:Protein Domains; D017510:Protein Folding; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012641:Selection, Genetic; D015398:Signal Transduction
chemical_list: D064267:Intrinsically Disordered Proteins; D011506:Proteins
keywords: conservation score; protein domain; protein folding; selection pressure; unstructured