Unprecedented islands of GGC and GCC repeats coincide with human evolution.

Abstract 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 on those STRs, (GGC)3 and (GCC)3 STRs remain widely unexplored. In a genome-wide search in human, here we mapped GGC and GCC STRs of ≥3-repeats, and report islands of up to 45 of those STRs, populating spans of 1 to 2 kb of genomic DNA with extraordinary density and periodicity. RGPD4 and NOC4L harbored the densest (GGC)3 (probability 3.09061E-71) and (GCC)3 (probability 1.72376E-61) STR islands, respectively, and were human-specific. We also found a prime instance of directional incremented density of STRs at a specific locus in human versus other species, that was the FOXK2 (GGC)3 island (probability 5.93916E-12). 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. In conclusion, (GGC)3 and (GCC)3 STRs form unprecedented islands of extraordinary density and periodicity, which may be of evolutionary significance in human evolution. These islands remain to be explored in evolutionary, mechanistic, and functional platforms.