De novo emergence and potential function of human-specific tandem repeats in brain-related loci.

ABSTRACT

Tandem repeats (TRs) are widespread in the genomes of all living organisms. In eukaryotes, they are found in both coding and noncoding regions and have potential roles in the regulation of cellular processes such as transcription, translation and in the modification of protein structure. Recent studies have highlighted TRs as a key regulator of gene expression and a potential contributor to human evolution. Thus, TRs are emerging as an important source of variation that can result in differential gene expression at intra- and inter-species levels. In this study, we performed a genome-wide survey to identify TRs that have emerged in the human lineage. We further examined these loci to explore their potential functional significance for human evolution. We identified 152 human-specific TR (HSTR) loci containing a repeat unit of more than ten bases, with most of them showing a repeat count of two. Gene set enrichment analysis showed that HSTR-associated genes were associated with biological functions in brain development and synapse function. In addition, we compared gene expression of human HSTR loci with orthologues from non-human primates (NHP) in seven different tissues. Strikingly, the expression level of HSTR-associated genes in brain tissues was significantly higher in human than in NHP. These results suggest the possibility that de novo emergence of TRs could have resulted in altered gene expression in humans within a short-time frame and contributed to the rapid evolution of human brain function.