Low-complexity regions in proteins as a source of evolutionary innovation

In this thesis we aimed to study evolutionary implications of low-complexity regions, protein sequences of very simple amino acid composition. Its uncontrolled expansion causes several human diseases, including Huntington’s disease and other neurodegenerative and developmental diseases. However, the...

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Detalles Bibliográficos
Autor: Radó i Trilla, Núria
Tipo de recurso: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2013
País:España
Institución:CBUC, CESCA
Repositorio:TDR. Tesis Doctorales en Red
OAI Identifier:oai:www.tdx.cat:10803/113603
Acceso en línea:http://hdl.handle.net/10803/113603
Access Level:acceso abierto
Palabra clave:Low-complexity regions
Amino acid tandem repeats
Simple sequence
Gene age
Protein domain evolution
Transcription factor
Paralogous protein
Repeticions en tandem d’aminoàcids
Seqüències simples
Edat dels gens
Evolució de dominis de proteïnes
Factor de transcripció
Proteïnes paràlogues
Regions de baixa complexitat
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616.8
Descripción
Sumario:In this thesis we aimed to study evolutionary implications of low-complexity regions, protein sequences of very simple amino acid composition. Its uncontrolled expansion causes several human diseases, including Huntington’s disease and other neurodegenerative and developmental diseases. However, they are surprisingly abundant in proteins, which seem paradoxical given their high pathogenic potential. Moreover, experimental data has shown that the formation of novel LCRs, or the modification of existing ones, can have functional consequences. First we wanted to perform a descriptive analysis of low-complexity regions in chordates focusing on lineage and age related features of LCR evolution. Second, we want to assess why low-complexity regions are so common in eukaryotic proteins. Two hypotheses have been proposed: on one hand, they may be an important source of genetic variability and might be involved in adaptive processes. To investigate whether LCRs are important players in the acquisition of novel functions, we examined transcription factor gene duplicates. On the other hand, low-complexity regions may also contribute to the formation of novel coding sequences, facilitating the generation of novel protein functions. We have tested this hypothesis by examining the content of low-complexity sequences in proteins of different age. Both analysis let us to conclude that low-complexity regions may be involved in protein diversification, either providing new functional sequences that will modify existing proteins or being involved in the formation of novel protein coding sequences.