Gain, loss and divergence in primate Zinc-Finger genes: A rich resource for evolution of gene regulatory differences between species

Katja Nowick, Christopher J Fields, Tim Gernat, Derek Caetano-Anolles, Nadezda Kholina, Lisa J Stubbs

Research output: Contribution to journalArticle

Abstract

The molecular changes underlying major phenotypic differences between humans and other primates are not well understood, but alterations in gene regulation are likely to play a major role. Here we performed a thorough evolutionary analysis of the largest family of primate transcription factors, the Krüppel-type zinc finger (KZNF) gene family. We identified and curated gene and pseudogene models for KZNFs in three primate species, chimpanzee, orangutan and rhesus macaque, to allow for a comparison with the curated set of human KZNFs. We show that the recent evolutionary history of primate KZNFs has been complex, including many lineage-specific duplications and deletions. We found 213 species-specific KZNFs, among them 7 human-specific and 23 chimpanzee-specific genes. Two human-specific genes were validated experimentally. Ten genes have been lost in humans and 13 in chimpanzees, either through deletion or pseudogenization. We also identified 30 KZNF orthologs with human-specific and 42 with chimpanzee-specific sequence changes that are predicted to affect DNA binding properties of the proteins. Eleven of these genes show signatures of accelerated evolution, suggesting positive selection between humans and chimpanzees. During primate evolution the most extensive re-shaping of the KZNF repertoire, including most gene additions, pseudogenizations, and structural changes occurred within the subfamily homininae. Using zinc finger (ZNF) binding predictions, we suggest potential impact these changes have had on human gene regulatory networks. The large species differences in this family of TFs stands in stark contrast to the overall high conservation of primate genomes and potentially represents a potent driver of primate evolution.

Original languageEnglish (US)
Article numbere21553
JournalPloS one
Volume6
Issue number6
DOIs
StatePublished - Jul 1 2011

Fingerprint

zinc finger motif
Zinc Fingers
Regulator Genes
regulator genes
Primates
Zinc
Genes
Pan troglodytes
genes
Pongo
Pseudogenes
Pongo pygmaeus
binding properties
pseudogenes
Gene Regulatory Networks
DNA-Binding Proteins
Macaca mulatta
interspecific variation
Gene expression
Transcription Factors

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Gain, loss and divergence in primate Zinc-Finger genes : A rich resource for evolution of gene regulatory differences between species. / Nowick, Katja; Fields, Christopher J; Gernat, Tim; Caetano-Anolles, Derek; Kholina, Nadezda; Stubbs, Lisa J.

In: PloS one, Vol. 6, No. 6, e21553, 01.07.2011.

Research output: Contribution to journalArticle

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