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.
Highlights
An increasing number of human protein-coding genes are unraveled to consist of alternative translation initiation sites (TISs), which are selected based on complex and yet not fully known scanning mechanisms [1, 2]
Short tandem repeat (STR) link to TIS selection on both genomic DNA and Complementary DNA (cDNA) platforms We examined the hypothesis that there may be a link between STRs and TIS selection
Our findings provide the first evidence of a link between STRs and TIS selection on both platforms
Summary
An increasing number of human protein-coding genes are unraveled to consist of alternative translation initiation sites (TISs), which are selected based on complex and yet not fully known scanning mechanisms [1, 2]. One of the important and understudied cis-regulatory elements affecting translation is short tandem repeats (STRs)/microsatellites. Arabfard et al Human Genomics (2018) 12:47 expansion of STRs in the RNA structure results in toxic RNAs and non-AUG translation and the development of several human-specific neurological [12,13,14]. Despite their vast biological implication, the relevance of short tandem repeats (STRs)/microsatellites to the protein-coding gene translation initiation sites (TISs) remains largely unknown
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