Directional Decremental Abundance of (GA)9 and (GA)11 Blocks in Primate Speciation

Abstract

Background: Recent evidence indicates that expansion of a number of short tandem repeats (STRs) may be a result of natural selection. The human neuron-specific genes, RIT2 and GPM6B, contain two of the longest GA-STRs at 11 and 9-repeats, respectively, the length ranges of which are functional, and exceedingly rare repeats at the extreme end of those STRs occur with major human disorders. To examine the evolutionary trend of (GA)11 and (GA)9 blocks, two sets of chromosomal regions (each spanning 10 Mb of genomic DNA) across all chromosomes, were searched for those blocks across rodent and primate orders. We also sequenced the RIT2 and GPM6B STRs in 600 human subjects, consisting of late-onset neurocognitive disorder (n=200), multiple sclerosis (n=100), and controls (n=200). Results: We detected a directional decremental abundance of (GA)11 and (GA)9 blocks, matching the phylogenetic distance of the selected species as follows: mouse>macaque>great apes (p=0.000006). The RIT2 and GPM6B GA-repeats were at strict lengths of 11 and 9-repeats in human, respectively, and were predominantly human-specific in formula. Exception included a 9/11 genotype of the RIT2 GA-STR in an isolate case of multiple sclerosis. Conclusion: We report the first evidence of massive directional trend of STRs linking to speciation. Genes such as RIT2 and GPM6B may be suitable candidates to explore the evolutionary impact of STR blocks.