The evolution of gene expression and binding specificity of the largest transcription factor family in primates

• DOI: 10.1111/evo.12819
• Publication Date: 2015-11-23T09:55:43Z
• Authors: Adamandia Kapopoulou; Lisha Mathew; Alex Wong; Didier Trono; Jeffrey D. Jensen
• Keywords: Nonsynonymous substitution; Negative selection; SNP

The KRAB-containing zinc finger (KRAB-ZF) proteins represent the largest family of transcription factors (TFs) in humans, yet for great majority, their function and specific genomic target remain unknown. However, it has been shown that a large fraction these genes arose from segmental duplications, they have expanded gene number throughout vertebrate evolution. To determine whether this expansion is linked to selective pressures acting on different domains, we manually curated all KRAB-ZF present human genome together with orthologous three closely related species assessed evolutionary forces at sequence level as well expression profiles. We provide evidence KRAB-ZFs can be separated into two categories according polymorphism DNA-contacting residues. Those carrying nonsynonymous single nucleotide (SNP) amino acids exhibit significantly reduced tissues, emerged recent lineage, seem less strongly constrained evolutionarily than those without such polymorphism. This work provides link between age TF, residues levels-both which may jointly affected by selection.