Validation of suitable reference genes for expression normalization in Echinococcus spp. larval stages

PLoS One. 2014 Jul 11;9(7):e102228. doi: 10.1371/journal.pone.0102228. eCollection 2014.

Abstract

In recent years, a significant amount of sequence data (both genomic and transcriptomic) for Echinococcus spp. has been published, thereby facilitating the analysis of genes expressed during a specific stage or involved in parasite development. To perform a suitable gene expression quantification analysis, the use of validated reference genes is strongly recommended. Thus, the aim of this work was to identify suitable reference genes to allow reliable expression normalization for genes of interest in Echinococcus granulosus sensu stricto (s.s.) (G1) and Echinococcus ortleppi upon induction of the early pre-adult development. Untreated protoscoleces (PS) and pepsin-treated protoscoleces (PSP) from E. granulosus s.s. (G1) and E. ortleppi metacestode were used. The gene expression stability of eleven candidate reference genes (βTUB, NDUFV2, RPL13, TBP, CYP-1, RPII, EF-1α, βACT-1, GAPDH, ETIF4A-III and MAPK3) was assessed using geNorm, Normfinder, and RefFinder. Our qPCR data showed a good correlation with the recently published RNA-seq data. Regarding expression stability, EF-1α and TBP were the most stable genes for both species. Interestingly, βACT-1 (the most commonly used reference gene), and GAPDH and ETIF4A-III (previously identified as housekeeping genes) did not behave stably in our assay conditions. We propose the use of EF-1α as a reference gene for studies involving gene expression analysis in both PS and PSP experimental conditions for E. granulosus s.s. and E. ortleppi. To demonstrate its applicability, EF-1α was used as a normalizer gene in the relative quantification of transcripts from genes coding for antigen B subunits. The same EF-1α reference gene may be used in studies with other Echinococcus sensu lato species. This report validates suitable reference genes for species of class Cestoda, phylum Platyhelminthes, thus providing a foundation for further validation in other epidemiologically important cestode species, such as those from the Taenia genus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cattle
  • Echinococcosis / parasitology
  • Echinococcus / genetics*
  • Echinococcus / growth & development
  • Echinococcus / isolation & purification
  • Echinococcus granulosus / genetics*
  • Echinococcus granulosus / growth & development
  • Echinococcus granulosus / isolation & purification
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Genes, Essential*
  • Genes, Helminth*
  • Life Cycle Stages / genetics*
  • Lipoproteins / genetics
  • Peptide Elongation Factor 1 / genetics
  • RNA, Helminth / genetics*
  • RNA, Messenger / genetics*

Substances

  • Lipoproteins
  • Peptide Elongation Factor 1
  • RNA, Helminth
  • RNA, Messenger
  • antigen B, Echinococcus granulosus

Grants and funding

This work was supported by CNPq (www.cnpq.br) and CAPES (www.capes.gov.br) grants. SME is a recipient of a CNPq fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.