Biochemical and Biophysical Research Communications
Simple repeat evolution includes dramatic primary sequence changes that conserve folding potential
Section snippets
Materials and methods
Database searches. We searched non-redundant 5′ and 3′ UTR databases (version, 2.2.1, 4-13-01, 368,154 sequences (http://bighost.area.ba.cnr.it/BIG/UTR-Home/) for all H. sapiens UTRs containing (AT)n ⩾ 7 [8]. We also searched H. sapiens genomic sequences designated as cDNAs at Ensembl[21]. Combining both databases, there were 235 total (AT)n ⩾ 7-containing UTRs reported for H. sapiens. Repeat flanking sequences consisting of 100 bp were then used to search all available genomes including: Bos Taurus
Sequences with folding potential replace one another during evolution
The H. sapiens Rabgap1 3′ UTR contained an uninterrupted (AT)n repeat. In M. musculus, this was replaced by a slightly interrupted (GT)n–(AC)n sequence combination (Fig. 1). Again, the actual replacement could have happened in the human rather than the rodent lineage. By themselves, (GT)n and (AC)n are weak-folding STRs. However, they are complementary and in combination have substantial, predicted folding energy similar to that of (AT)n by itself (Fig. 1). The predicted mouse Rabgap1 stem has
Discussion
It is difficult to explain the reported replacements and variations in primary sequence without invoking selection to preserve secondary structure. Conservation of secondary structure potential has proven valuable for identifying both known and previously unsuspected fRNAs [4]. Regardless of folding parameter choices, or whether the precise structures form, the hypothesis that simple repeats were selected for their secondary structure potential accurately predicted simple repeat replacements,
Acknowledgments
This study was supported by an NIH RO1 Grant DK38955 and a Veteran Affairs Merit Review Award, Bacterial DNA in Prostate Disease.
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