1st International and 10th National Iranian Conference on Bioinformatics
Tandem repeats ubiquitously flank and contribute to translation initiation sites
Paper ID : 1295-ICB10
Authors:
Ali Mohammad Ali Maddi1, Kaveh Kavousi *1, مسعود عرب فرد2, حمید اوحدی3, مینا اوحدی4
1University of Tehran
2دانشگاه علوم پزشکی بقیه الله
3University of St. Andrews
4دانشگاه علوم توانبخشی و سلامت اجتماعی
Abstract:
Background: Recent findings in yeast and human suggest that evolutionary divergence in cis-regulatory sequences can impact translation initiation sites (TISs)(1, 2). Here we employed the TIS homology concept to study a possible link between every category of tandem repeats (TRs) and TIS selection(3, 4).
Materials and Methods: We selected human as reference, and 83 other species, and extracted the entire protein-coding genes (n=1,611,368) and transcripts (n=2,730,515) annotated for those species from Ensembl 102. Two different weighing vectors were implemented to designate homologous vs. non-homologous TISs. The threshold for TIS homology was set based on three thousand simulations of random pair-wise comparisons of the initial five amino acids (excluding the initial methionine) of protein-coding genes in human. TISs that were flanked by TRs in human were BLASTed against the initial TISs in the orthologous genes across the 83 species, and the number of events in which human-specific and non-specific TRs occurred with homologous (≥ 50% homology) and non-homologous (<50% homology) TISs were subsequently calculated. On average, every transcript was flanked by 1.19 TRs of various categories in their 120 bp upstream RNA sequence.
Results and Conclusion: We detected statistically significant excess of non-homologous TISs co-occurring with human-specific TRs and vice versa (on average, significant p-values << 0.1 near the zero were calculated for all experiments). At the interspecies level, human proteins flanked by human-specific TRs were significantly less homologous to other species than those flanked by non-specific TRs. We conclude that TRs are abundant cis-elements in the upstream sequences of TISs across species. We also conclude a link between all categories of TRs and TIS selection based on the patterns of co-occurrence of TRs with TISs. Asymmetric and stem-loop structures formed as a result of TRs may function as genetic marks for TIS selection.
Keywords:
Translation initiation site; tandem repeat; genome-scale; TIS selection; homology
Status : Paper Accepted (Poster Presentation)