Comparative genomics in Chlamydomonas and Plasmodium identifies an ancient nuclear envelope protein family essential for sexual reproduction in protists, fungi, plants, and vertebrates

Genes Dev. 2013 May 15;27(10):1198-215. doi: 10.1101/gad.212746.112.


Fertilization is a crucial yet poorly characterized event in eukaryotes. Our previous discovery that the broadly conserved protein HAP2 (GCS1) functioned in gamete membrane fusion in the unicellular green alga Chlamydomonas and the malaria pathogen Plasmodium led us to exploit the rare biological phenomenon of isogamy in Chlamydomonas in a comparative transcriptomics strategy to uncover additional conserved sexual reproduction genes. All previously identified Chlamydomonas fertilization-essential genes fell into related clusters based on their expression patterns. Out of several conserved genes in a minus gamete cluster, we focused on Cre06.g280600, an ortholog of the fertilization-related Arabidopsis GEX1. Gene disruption, cell biological, and immunolocalization studies show that CrGEX1 functions in nuclear fusion in Chlamydomonas. Moreover, CrGEX1 and its Plasmodium ortholog, PBANKA_113980, are essential for production of viable meiotic progeny in both organisms and thus for mosquito transmission of malaria. Remarkably, we discovered that the genes are members of a large, previously unrecognized family whose first-characterized member, KAR5, is essential for nuclear fusion during yeast sexual reproduction. Our comparative transcriptomics approach provides a new resource for studying sexual development and demonstrates that exploiting the data can lead to the discovery of novel biology that is conserved across distant taxa.

Keywords: Chlamydomonas; KAR5/GEX1/Brambleberry; Plasmodium; RNA sequencing; fertilization; nuclear envelope fusion.

Publication types

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

MeSH terms

  • Animals
  • Arabidopsis Proteins / classification
  • Arabidopsis Proteins / metabolism
  • Chlamydomonas / genetics*
  • Fertilization / genetics
  • Fungi / genetics*
  • Fungi / growth & development
  • Gene Expression Profiling
  • Genes, Essential*
  • Meiosis
  • Membrane Proteins / classification
  • Membrane Proteins / metabolism
  • Nuclear Envelope / metabolism*
  • Nuclear Proteins / classification*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Plants / genetics
  • Plasmodium / genetics*
  • Reproduction / genetics
  • Saccharomyces cerevisiae Proteins / classification
  • Saccharomyces cerevisiae Proteins / metabolism
  • Transcriptome / genetics
  • Vertebrates / genetics*


  • Arabidopsis Proteins
  • GEX1 protein, Arabidopsis
  • KAR5 protein, S cerevisiae
  • Membrane Proteins
  • Nuclear Proteins
  • Saccharomyces cerevisiae Proteins