Unstable Tandem Repeats in Promoters Confer Transcriptional Evolvability

FAS Center for Systems Biology, Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA.
Science (Impact Factor: 33.61). 06/2009; 324(5931):1213-6. DOI: 10.1126/science.1170097
Source: PubMed


Relative to most regions of the genome, tandemly repeated DNA sequences display a greater propensity to mutate. A search for tandem repeats in the Saccharomyces cerevisiae genome revealed that the nucleosome-free region directly upstream of genes (the promoter region) is enriched in repeats. As many as 25% of all gene promoters contain tandem repeat sequences. Genes driven by these repeat-containing promoters show significantly higher rates of transcriptional divergence. Variations in repeat length result in changes in expression and local nucleosome positioning. Tandem repeats are variable elements in promoters that may facilitate evolutionary tuning of gene expression by affecting local chromatin structure.

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    • "However, recent studies have identified functional microsatellites that affect the physical aspect of an individual (Kashi and King 2006, Gemayel et al. 2010, Padeken et al. 2015). These putative functional microsatellites are primarily located in or near gene regions, and there is variation in the number of times that the motif is repeated, which is related to the ability of the microsatellites to modify gene expression or change protein sequences (Wren et al. 2000, Li et al. 2004, Vinces et al. 2009, Gemayel et al. 2010). In addition to this functional aspect, repetitive DNA variants that include microsatellites may serve as efficient agents for adaptive evolution (King and Kashi 2009). "
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    • "Microsatellites located in the promoter regions are known to regulate gene expression of organisms ranging from bacteria to human (Swaya et al. 2012). Variable repeats within the yeast promoter have been shown to modulate promoter structure and transcription factor binding (Vinces et al. 2009). "
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    • "In other cases, such as oculopharyngeal muscular dystrophy, a pathogenic allele is only two repeat units from the wild-type allele (Brais et al. 1998; Amiel et al. 2004). In addition to Mendelian conditions, multiple studies have suggested that STR variations contribute to an array of complex traits (Gemayel et al. 2010), ranging from the period of the circadian clock in Drosophila (Sawyer et al. 1997) to gene expression in yeast (Vinces et al. 2009) and splicing in humans (Hefferon et al. 2004; Sathasivam et al. 2013). Beyond their importance to medical genetics, STR variations convey high information content due to their rapid mutations and multiallelic spectra. "
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