title: Exceptional expansion and conservation of a CT-repeat complex in the core promoter of PAXBP1 in primates.
abstract: 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.
authors.affiliation: Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
authors.forename: Saeid
authors.initials: S
authors.lastname: Mohammadparast
authors.forename: Hadi
authors.initials: H
authors.lastname: Bayat
authors.forename: Akbar
authors.initials: A
authors.lastname: Biglarian
authors.forename: Mina
authors.initials: M
authors.lastname: Ohadi
mesh_terms: D000818:Animals; D005075:Biological Evolution; D030541:Databases, Genetic; D014644:Genetic Variation; D057809:HEK293 Cells; D006801:Humans / Q000235:genetics; D018895:Microsatellite Repeats / Q000235:genetics*; D011323:Primates / Q000235:genetics*; D011401:Promoter Regions, Genetic
keywords: CT-repeat; Homo sapiens; PAXBP1; core promoter; evolution; primate