Tandem repeats ubiquitously flank and contribute to translation initiation sites

Background: While the evolutionary divergence of cis -regulatory sequences impacts translation initiation sites (TISs), the implication of tandem repeats (TRs) in TIS selection remains elusive for the most part. Hence, here we employed the TIS homology concept to study the co-occurrence patterns of all categories of TRs with TISs. Methods: : Human, as reference sequence, and 83 other species were selected, and data was extracted on 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 employed to assign TIS homology, and the results were assessed in 10-fold validation. Results: : On average, every TIS was flanked by 1.19 TRs of various categories within the 120 bp upstream sequence. We detected statistically significant enrichment of non-homologous TISs co-occurring with human-specific TRs. On the contrary, homologous TISs co-occurred significantly with non-human-specific TRs. 2,991 human genes had at least one transcript flanked by a human-specific TR in their upstream flanking region, and nervous system development was the top enriched ontology term across those genes. Text mining of a number of the identified genes such as MYH2 , TTN , SLC6A8 , CACNA1A , and EIF5AL1 yielded predominant expression and functions in the human brain and skeletal muscle. Conclusion: We conclude that TRs are abundant cis elements in the upstream sequences of TISs across species, and there may be a link between all categories of TRs and TIS selection. The potential biological consequences of this link are discussed in human as the reference sequence in this study.