Novel islands of GGC and GCC repeats coincide with human evolution

Because of high mutation rate, overrepresentation in genic regions, and link with various neurological, neurodegenerative, and movement disorders, GGC and GCC short tandem repeats (STRs) are prone to natural selection. Among a number of lacking data, the 3-repeats of these STRs remain widely unexplored.

In a genome-wide search in human, here we mapped GGC and GCC STRs of ≥3-repeats, and found novel islands of up to 45 of those STRs, populating spans of 1 to 2 kb of genomic DNA. RGPD4 and NOC4L harbored the densest (GGC)3 (probability 3.09061E-71) and (GCC)3 (probability 1.72376E-61) islands, respectively, and were human-specific. We also found prime instances of directional incremented density of STRs at specific loci in human versus other species, including the FOXK2 and SKI GGC islands. The genes containing those islands significantly diverged in expression in human versus other species, and the proteins encoded by those genes interact closely in a physical interaction network, consequence of which may be human-specific characteristics such as higher order brain functions.

We report novel islands of GGC and GCC STRs of evolutionary relevance to human. The density, and in some instances, periodicity of these islands support them as a novel genomic entity, which need to be further explored in evolutionary, mechanistic, and functional platforms.