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

TitleExon-phase symmetry and intrinsic structural disorder promote modular evolution in the human genome.
Publication TypeJournal Article
Year of Publication2013
AuthorsSchad, E., L. Kalmar, and P. Tompa
JournalNucleic Acids Res
Volume41
Issue8
Pagination4409-22
Date Published2013 Apr
Type of Articleidp
ISSN1362-4962
KeywordsEvolution, Molecular, Exons, Genome, Human, Humans, Protein Conformation, Proteins
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.

DOI10.1093/nar/gkt110
Alternate JournalNucleic Acids Res.
PubMed ID23460204
PubMed Central IDPMC3632108