Comparative bioinformatics analysis of transcription factor genes indicates conservation of key regulatory domains among babesia bovis, babesia microti and theileria equi.

Authors: ALZAN, H - Washington State University; Knowles Jr, Donald; Suarez, Carlos

Submitted to: PLOS Neglected Tropical Diseases
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/11/2016
Publication Date: 11/10/2016
Citation: Alzan, H.F., Knowles, D.P., Suarez, C.E. 2016. Comparative bioinformatics analysis of transcription factor genes indicates conservation of key regulatory domains among babesia bovis, babesia microti and theileria equi. PLOS Neglected Tropical Diseases. doi:1371/journal.pntd.0004983.

Interpretive Summary: The tick borne apicomplexan parasites Babesia and Theileria are responsible for costly and devastating diseases globally. Improved control is needed but the biology of these parasites remains poorly understood. Significant gaps include better understanding of the mechanisms involved in gene control expression, and the events leading to parasite development among hosts, including the development of sexual stages in their definitive tick vector hosts. Similar to other better studied eukaryotic cells, it is likely that regulatory genes coding for DNA binding proteins such as members of the Api-AP2, HMG and Myb families play crucial roles as transcription factors in these processes, but these genes remain uncharacterized in these three related parasites. In this study we describe the presence and genomic organization of these three types of genes in Babesia bovis, B. microti and Theileria equi, highlighting the importance of the conservation of these genes and their possible contributions to parasite development thorough their different life stages. We also describe the occurrence of a previously unnoticed HMG gene in B. microti, an important emerging human pathogen, defined the repertoire of eight conserved Myb genes, and we describe the pattern of transcription of the regulatory AP2, HMG and Myb genes in B. bovis intra-erythrocytic stages for the first time. It is expected that these findings will elicit more basic research in this field and contribute to the development of converged intervention strategies for the improved control of these devastating and generally neglected diseases

Technical Abstract: Apicomplexa tick borne hemoparasites including B. bovis, B. microti, and Theileria equi are responsible for bovine and human babesiosis and equine theileriosis respectively. These neglected 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 the three parasite’s genomes; ii] identify a previously unreported HMG gene in B. microti; iii] define a repertoire of eight conserved Myb genes, and iv] identify ApiAP2 correlates among B. bovis and the better studied Plasmodium parasites. Searching the available transcriptome of B. bovis defined patterns of transcription of these three genes in B. bovis erythrocyte stage parasites. Sequence comparisons suggest conservation of functional domains and general architecture in the ApiAP2, 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, T. equi, and B. microti life cycle and environmental adaptive responses, and may contribute to the development of novel convergent strategies for improved control of babesiosis and equine piroplasmosis.