Link between short tandem repeats and translation initiation site selection

Abstract

BackgroundDespite their vast biological implication, the relevance of short tandem repeats (STRs)/microsatellites to the protein-coding gene translation initiation sites (TISs) remains largely unknown.MethodsWe performed an Ensembl-based comparative genomics study of all annotated orthologous TIS-flanking sequences in human and 46 other species across vertebrates, on the genomic DNA and cDNA platforms (755,956 TISs), aimed at identifying human-specific STRs in this interval. The collected data were used to examine the hypothesis of a link between STRs and TISs. BLAST was used to compare the initial five amino acids (excluding the initial methionine), codons of which were flanked by STRs in human, with the initial five amino acids of all annotated proteins for the orthologous genes in other vertebrates (total of 5,314,979 pair-wise TIS comparisons on the genomic DNA and cDNA platforms) in order to compare the number of events in which human-specific and non-specific STRs occurred with homologous and non-homologous TISs (i.e., ≥ 50% and < 50% similarity of the five amino acids).ResultsWe detected differential distribution of the human-specific STRs in comparison to the overall distribution of STRs on the genomic DNA and cDNA platforms (Mann Whitney U test p = 1.4 × 10−11 and p < 7.9 × 10−11, respectively). We also found excess occurrence of non-homologous TISs with human-specific STRs and excess occurrence of homologous TISs with non-specific STRs on both platforms (p < 0.00001).ConclusionWe propose a link between STRs and TIS selection, based on the differential co-occurrence rate of human-specific STRs with non-homologous TISs and non-specific STRs with homologous TISs.Electronic supplementary materialThe online version of this article (10.1186/s40246-018-0181-3) contains supplementary material, which is available to authorized users.

Patterns of microsatellite distribution across eukaryotic genomes

“…Repeat elements have long been thought to have functional, mutational and evolutionary significance [25, 26] and experimental evidence of a role for SSRs is increasingly available, albeit in only a few species per study (reviewed in [27]). While this manuscript was being reviewed, another study was published that showed differential distribution of human-specific SSRs at translation initiation sites [28] with implications for directing species-specific translation events and thus the phenotype. Such studies bolster recent work on the evolutionary trends and influence of SSRs in defining species specificity and warrant larger scale analysis across the evolutionary landscape.…”

The Short Tandem Repeat of the DMT1 Gene as a Molecular Marker of Elite Long-Distance Runners

“…(1) The STR polymorphisms might lead to alternative splicing of the DMT1 gene. A recent study has proposed that there is a link between short tandem repeats and translation initiation site selection in humans [31]. Previous studies have reported the existence of isoforms of DMT1 mRNA [32, 33] and protein [33], suggesting alternative splicing of the DMT1 gene.…”

Tandem repeats ubiquitously flank and select translation initiation sites

“…Based on a TIS homology approach, we recently reported a link between STRs and TIS selection (31). Here, we extended our weighing methods, and developed a comprehensive software package, to study a possible link between all categories of TRs and TIS selection across 84 species.…”