Synonymous Constraint Elements Show a Tendency to Encode Intrinsically Disordered Protein Segments

Macossay-Castillo, Mauricio and Kosol, Simone and Tompa, Péter and Pancsa, Rita (2014) Synonymous Constraint Elements Show a Tendency to Encode Intrinsically Disordered Protein Segments. PLOS COMPUTATIONAL BIOLOGY, 10 (5). e1003607. ISSN 1553-734X


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Synonymous constraint elements (SCEs) are protein-coding genomic regions with very low synonymous mutation rates believed to carry additional, overlapping functions. Thousands of such potentially multi-functional elements were recently discovered by analyzing the levels and patterns of evolutionary conservation in human coding exons. These elements provide a good opportunity to improve our understanding of how the redundant nature of the genetic code is exploited in the cell. Our premise is that the protein segments encoded by such elements might better comply with the increased functional demands if they are structurally less constrained (i.e. intrinsically disordered). To test this idea, we investigated the protein segments encoded by SCEs with computational tools to describe the underlying structural properties. In addition to SCEs, we examined the level of disorder, secondary structure, and sequence complexity of protein regions overlapping with experimentally validated splice regulatory sites. We show that multi-functional gene regions translate into protein segments that are significantly enriched in structural disorder and compositional bias, while they are depleted in secondary structure and domain annotations compared to reference segments of similar lengths. This tendency suggests that relaxed protein structural constraints provide an advantage when accommodating multiple overlapping functions in coding regions. © 2014 Macossay-Castillo et al.

Item Type: Article
Uncontrolled Keywords: synonymous constraint element; structure analysis; RNA Splicing; PROTEIN SECONDARY STRUCTURE; PROTEIN FUNCTION; protein domain; protein defect; mathematical computing; GENOMICS; Genetic regulation; genetic code; gene function; controlled study; ARTICLE; amino acid sequence; PROTEIN
Subjects: Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia
Depositing User: MTMT SWORD
Date Deposited: 25 Jun 2014 12:51
Last Modified: 25 Jun 2014 12:51

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