Comparative Bioinformatics Analysis of Transcription Factor Genes Indicates Conservation of Key Regulatory Domains among Babesia bovis, Babesia microti, and Theileria equi

PLoS Negl Trop Dis. 2016 Nov 10;10(11):e0004983. doi: 10.1371/journal.pntd.0004983. eCollection 2016 Nov.

Abstract

Apicomplexa tick-borne hemoparasites, including Babesia bovis, Babesia microti, and Theileria equi are responsible for bovine and human babesiosis and equine theileriosis, respectively. These parasites of vast medical, epidemiological, and economic impact have complex life cycles in their vertebrate and tick hosts. Large gaps in knowledge concerning the mechanisms used by these parasites for gene regulation remain. Regulatory genes coding for DNA binding proteins such as members of the Api-AP2, HMG, and Myb families are known to play crucial roles as transcription factors. Although the repertoire of Api-AP2 has been defined and a HMG gene was previously identified in the B. bovis genome, these regulatory genes have not been described in detail in B. microti and T. equi. In this study, comparative bioinformatics was used to: (i) identify and map genes encoding for these transcription factors among three parasites' genomes; (ii) identify a previously unreported HMG gene in B. microti; (iii) define a repertoire of eight conserved Myb genes; and (iv) identify AP2 correlates among B. bovis and the better-studied Plasmodium parasites. Searching the available transcriptome of B. bovis defined patterns of transcription of these three gene families in B. bovis erythrocyte stage parasites. Sequence comparisons show conservation of functional domains and general architecture in the AP2, Myb, and HMG proteins, which may be significant for the regulation of common critical parasite life cycle transitions in B. bovis, B. microti, and T. equi. A detailed understanding of the role of gene families encoding DNA binding proteins will provide new tools for unraveling regulatory mechanisms involved in B. bovis, B. microti, and T. equi life cycles and environmental adaptive responses and potentially contributes to the development of novel convergent strategies for improved control of babesiosis and equine piroplasmosis.

Publication types

  • Comparative Study
  • Review

MeSH terms

  • Animals
  • Babesia bovis / genetics*
  • Babesia microti / genetics*
  • Babesiosis / parasitology
  • Base Sequence
  • Cattle
  • Computational Biology / methods
  • DNA-Binding Proteins / genetics
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Genome, Protozoan*
  • Horse Diseases / parasitology
  • Horses / parasitology
  • Humans
  • Life Cycle Stages / genetics
  • Phylogeny
  • Sequence Analysis, DNA
  • Theileria / genetics*
  • Theileriasis / parasitology
  • Transcription Factors / genetics*

Substances

  • DNA-Binding Proteins
  • Transcription Factors

Grants and funding

This work was supported by United States Department of Agriculture Research Service Current Research Information System Project No. 5348-32000-028-00D, and Egyptian government, Ministry of High Education and Scientific Research scholarship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.