KLF/SP Transcription Factor Family Evolution: Expansion, Diversification, and Innovation in Eukaryotes

Genome Biol Evol. 2015 Jul 30;7(8):2289-309. doi: 10.1093/gbe/evv141.


The Krüppel-like factor and specificity protein (KLF/SP) genes play key roles in critical biological processes including stem cell maintenance, cell proliferation, embryonic development, tissue differentiation, and metabolism and their dysregulation has been implicated in a number of human diseases and cancers. Although many KLF/SP genes have been characterized in a handful of bilaterian lineages, little is known about the KLF/SP gene family in nonbilaterians and virtually nothing is known outside the metazoans. Here, we analyze and discuss the origins and evolutionary history of the KLF/SP transcription factor family and associated transactivation/repression domains. We have identified and characterized the complete KLF/SP gene complement from the genomes of 48 species spanning the Eukarya. We have also examined the phylogenetic distribution of transactivation/repression domains associated with this gene family. We report that the origin of the KLF/SP gene family predates the divergence of the Metazoa. Furthermore, the expansion of the KLF/SP gene family is paralleled by diversification of transactivation domains via both acquisitions of pre-existing ancient domains as well as by the appearance of novel domains exclusive to this gene family and is strongly associated with the expansion of cell type complexity.

Keywords: C2H2 zinc fingers; domain architecture; domain co-occurrence network; domain evolution; domain shuffling; low-complexity regions.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Eukaryota / genetics
  • Evolution, Molecular*
  • Kruppel-Like Transcription Factors / chemistry
  • Kruppel-Like Transcription Factors / classification
  • Kruppel-Like Transcription Factors / genetics*
  • Molecular Sequence Data
  • Multigene Family*
  • Phylogeny
  • Protein Structure, Tertiary
  • Repressor Proteins / chemistry
  • Sp Transcription Factors / chemistry
  • Sp Transcription Factors / classification
  • Sp Transcription Factors / genetics*
  • Trans-Activators / chemistry
  • Zinc Fingers


  • Kruppel-Like Transcription Factors
  • Repressor Proteins
  • Sp Transcription Factors
  • Trans-Activators

Associated data

  • GENBANK/KJ576841
  • GENBANK/KJ576842