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

Adamandia Kapopoulou, Lisha Mathew, Alex Wong, Didier Trono, Jeffrey Jensen

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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

Original languageEnglish (US)
Pages (from-to)167-180
Number of pages14
JournalEvolution
Volume70
Issue number1
DOIs
StatePublished - Jan 1 2016
Externally publishedYes

Fingerprint

primate
Primates
gene expression
zinc finger motif
Zinc Fingers
polymorphism
Transcription Factors
transcription factors
Gene Expression
gene
zinc
genetic polymorphism
DNA
Genes
genes
Genomic Segmental Duplications
Age Factors
Human Genome
single nucleotide polymorphism
Single Nucleotide Polymorphism

Keywords

  • DNA-contacting residues
  • Endogenous retroelements
  • KRAB-containing zinc finger genes
  • Population genetics
  • Regulatory evolution
  • Transcription factors

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Ecology, Evolution, Behavior and Systematics
  • Genetics

Cite this

The evolution of gene expression and binding specificity of the largest transcription factor family in primates. / Kapopoulou, Adamandia; Mathew, Lisha; Wong, Alex; Trono, Didier; Jensen, Jeffrey.

In: Evolution, Vol. 70, No. 1, 01.01.2016, p. 167-180.

Research output: Contribution to journalArticle

Kapopoulou, Adamandia ; Mathew, Lisha ; Wong, Alex ; Trono, Didier ; Jensen, Jeffrey. / The evolution of gene expression and binding specificity of the largest transcription factor family in primates. In: Evolution. 2016 ; Vol. 70, No. 1. pp. 167-180.
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