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Exon-phase symmetry and intrinsic structural disorder promote modular evolution in the human genome

Schád, Éva and Kalmár, Lajos and Tompa, Péter (2013) Exon-phase symmetry and intrinsic structural disorder promote modular evolution in the human genome. Nucleic Acids Research, 41 (8). pp. 4409-4422. ISSN 0305-1048 (print), 1362-4962 (online)

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Abstract

A key signature of module exchange in the genome is phase symmetry of exons, suggestive of exon shuffling events that occurred without disrupting translation reading frame. At the protein level, intrinsic structural disorder may be another key element because disordered regions often serve as functional elements that can be effectively integrated into a protein structure. Therefore, we asked whether exon-phase symmetry in the human genome and structural disorder in the human proteome are connected, signalling such evolutionary mechanisms in the assembly of multi-exon genes. We found an elevated level of structural disorder of regions encoded by symmetric exons and a preferred symmetry of exons encoding for mostly disordered regions (>70% predicted disorder). Alternatively spliced symmetric exons tend to correspond to the most disordered regions. The genes of mostly disordered proteins (>70% predicted disorder) tend to be assembled from symmetric exons, which often arise by internal tandem duplications. Preponderance of certain types of short motifs (e.g. SH3-binding motif) and domains (e.g. high-mobility group domains) suggests that certain disordered modules have been particularly effective in exon-shuffling events. Our observations suggest that structural disorder has facilitated modular assembly of complex genes in evolution of the human genome. © 2013 The Author(s).

Item Type: Article
Uncontrolled Keywords: protein motif; protein domain; protein assembly; priority journal; PREDICTION; molecular evolution; human genome; gene duplication; exon shuffling; ARTICLE; alternative RNA splicing
Subjects: Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia
SWORD Depositor: MTMT SWORD
Depositing User: MTMT SWORD
Date Deposited: 05 Nov 2013 09:29
Last Modified: 05 Nov 2013 09:29
URI: http://real.mtak.hu/id/eprint/7125

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