Exceptional expansion and conservation of a CT‐repeat complex in the core promoter of PAXBP1 in primates

Adaptive evolution may be linked with the genomic distribution and function of short tandem repeats (STRs). Proximity of the core promoter STRs to the +1 transcription start site (TSS), and their mutable nature are characteristics that highlight those STRs as a novel source of interspecies variation. The PAXBP1 gene (alternatively known as GCFC1 ) core promoter contains the longest STR identified in a Homo sapiens gene core promoter. Indeed, this core promoter is a stretch of four consecutive CT‐STRs. In the current study, we used the Ensembl, NCBI, and UCSC databases to analyze the evolutionary trend and functional implication of this CT‐STR complex in six major lineages across vertebrates, including primates, non‐primate mammals, birds, reptiles, amphibians, and fish. We observed exceptional expansion (≥4‐repeats) and conservation of this CT‐STR complex across primates, except prosimians, Microcebus murinus and Otolemur garnettii (Fisher exact P  < 4.1 × 10 −7 ). H. sapiens has the most complex STR formula, and longest repeats. Macaca mulatta and Callithrix jacchus monkeys have the simplest STR formulas, and shortest repeat numbers. CT ≥4‐repeats were not detected in non‐primate lineages. Different length alleles across the PAXBP1 core promoter CT‐STRs significantly altered gene expression in vitro ( P  < 0.001, t‐test). PAXBP1 has a crucial role in craniofacial development, myogenesis, and spine morphogenesis, properties that have been diverged between primates and non‐primates. To our knowledge, this is the first instance of expansion and conservation of a STR complex co‐occurring specifically with the primate lineage. Am. J. Primatol. 76:747–756, 2014. © 2014 Wiley Periodicals, Inc.