Tandem repeats ubiquitously flank and contribute to translation initiation sites

Background: Recent findings in yeast and human suggest that evolutionary divergence in cis-regulatorysequences can impact translation initiation sites (TISs). Here we employed the TIS homology concept tostudy a possible link between every category of tandem repeats (TRs) and TIS selection.Materials and Methods: We selected human as reference, and ۸۳ other species, and extracted the entireprotein-coding genes (n=۱,۶۱۱,۳۶۸) and transcripts (n=۲,۷۳۰,۵۱۵) annotated for those species from Ensembl۱۰۲. 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-wisecomparisons of the initial five amino acids (excluding the initial methionine) of protein-coding genes inhuman. TISs that were flanked by TRs in human were BLASTed against the initial TISs in the orthologousgenes across the ۸۳ species, and the number of events in which human-specific and non-specific TRs occurredwith homologous (≥ ۵۰% homology) and non-homologous (<۵۰% homology) TISs were subsequentlycalculated. On average, every transcript was flanked by ۱.۱۹ TRs of various categories in their ۱۲۰ bpupstream RNA sequence.Results and Conclusion: We detected statistically significant excess of non-homologous TISs co-occurringwith human-specific TRs and vice versa (on average, significant p-values << ۰.۱ near the zero were calculatedfor all experiments). At the interspecies level, human proteins flanked by human-specific TRs weresignificantly less homologous to other species than those flanked by non-specific TRs. We conclude that TRsare abundant cis-elements in the upstream sequences of TISs across species. We also conclude a link betweenall categories of TRs and TIS selection based on the patterns of co-occurrence of TRs with TISs. Asymmetricand stem-loop structures formed as a result of TRs may function as genetic marks for TIS selection.

کلیدواژه ها:

Translation initiation site ، tandem repeat ، genome-scale ، TIS selection ، homology