An exceptionally long CA-repeat in the core promoter of SCGB2B2 links with the evolution of apes and Old World monkeys

• An exceptionally long CA-repeat in the core promoter of SCGB2B2 links with the evolution of apes and Old World monkeys.
• The SCGB2B2 core promoter CA-repeat up-regulates gene expression.
• Indicated role of SCGB2B2 core promoter CA-repeat as “expression code” for the evolution of apes and Old World monkeys.
• Genome-wide data on the evolutionary trend of human exceptionally long (≥ 6-repeats) core promoter CA-STRs.

We have recently reported a genome-scale catalog of human protein-coding genes that contain “exceptionally long” STRs (≥ 6-repeats) in their core promoter, which may be of selective advantage in this species. At the top of that list, SCGB2B2 (also known as SCGBL), contains one of the longest CA-repeat STRs identified in a human gene core promoter, at 25-repeats. In the study reported here, we analyzed the conservation status of this CA-STR across evolution. The functional implication of this STR to alter gene expression activity was also analyzed in the HEK-293 cell line. We report that the SCGB2B2 core promoter CA-repeat reaches exceptional lengths, ranging from 9- to 25-repeats, across Apes (Hominoids) and the Old World monkeys (CA > 2-repeats were not detected in any other species). The longest CA-repeats and highest identity in the SCGB2B2 protein sequence were observed between human and bonobo. A trend for increased gene expression activity was observed from the shorter to the longer CA-repeats (p < 0.009), and the CA-repeat increased gene expression activity, per se (p < 0.02). We propose that the SCGB2B2 gene core promoter CA-repeat functions as an expression code for the evolution of Apes and the Old World monkeys.