The Cryptosporidium parvum ApiAP2 gene family: insights into the evolution of apicomplexan AP2 regulatory systems

Nucleic Acids Res. 2014 Jul;42(13):8271-84. doi: 10.1093/nar/gku500. Epub 2014 Jun 23.


We provide the first comprehensive analysis of any transcription factor family in Cryptosporidium, a basal-branching apicomplexan that is the second leading cause of infant diarrhea globally. AP2 domain-containing proteins have evolved to be the major regulatory family in the phylum to the exclusion of canonical regulators. We show that apicomplexan and perkinsid AP2 domains cluster distinctly from other chromalveolate AP2s. Protein-binding specificity assays of C. parvum AP2 domains combined with motif conservation upstream of co-regulated gene clusters allowed the construction of putative AP2 regulons across the in vitro life cycle. Orthologous Apicomplexan AP2 (ApiAP2) expression has been rearranged relative to the malaria parasite P. falciparum, suggesting ApiAP2 network rewiring during evolution. C. hominis orthologs of putative C. parvum ApiAP2 proteins and target genes show greater than average variation. C. parvum AP2 domains display reduced binding diversity relative to P. falciparum, with multiple domains binding the 5'-TGCAT-3', 5'-CACACA-3' and G-box motifs (5'-G[T/C]GGGG-3'). Many overrepresented motifs in C. parvum upstream regions are not AP2 binding motifs. We propose that C. parvum is less reliant on ApiAP2 regulators in part because it utilizes E2F/DP1 transcription factors. C. parvum may provide clues to the ancestral state of apicomplexan transcriptional regulation, pre-AP2 domination.

Publication types

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

MeSH terms

  • Alveolata / genetics
  • Apicomplexa / genetics
  • Binding Sites
  • Cryptosporidium parvum / genetics*
  • Cryptosporidium parvum / metabolism
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / classification
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Evolution, Molecular
  • Gene Regulatory Networks
  • Multigene Family*
  • Nucleotide Motifs
  • Phylogeny
  • Plasmodium falciparum / genetics
  • Protein Structure, Tertiary
  • Transcription Factors / chemistry
  • Transcription Factors / classification*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • DNA-Binding Proteins
  • Transcription Factors