Evolution of dyskinetoplastic trypanosomes: how, and how often?

General rights Copyright for the publications made accessible via the Edinburgh Research Explorer is retained by the author(s) and / or other copyright owners and it is a condition of accessing these publications that users recognise and abide by the legal requirements associated with these rights. Take down policy The University of Edinburgh has made every reasonable effort to ensure that Edinburgh Research Explorer content complies with UK legislation. If you believe that the public display of this file breaches copyright please contact [email protected] providing details, and we will remove access to the work immediately and investigate your claim. Trypanosoma equiperdum and T. evansi are close relatives of T. brucei brucei that have lost all, or critical parts, of their mitochondrial DNA (mtDNA, kinetoplast or kDNA), thus known as dyskinetoplastic (Box 1) [1]. Transmission of T. equiperdumand T. evansi between mammals occurs mechanically: venereally in case of the former and mostly via biting flies in case of the latter [4]. This permits their wide geographical distribution, while T. brucei, dependent on cyclical development in the tsetse vector, is restricted to sub-Saharan Africa. T. brucei kDNA consists of 40–50 maxicircles, the equivalent of mtDNA in other organisms, and thousands of heterogeneous minicircles, which encode the guide RNAs (gRNAs) required for editing of maxicircle-encoded mRNAs [10]. Different minicircle classes encode different gRNA sets, and T. brucei kDNA contains an estimated 300–400 classes [1]. All T. equiperdum and T. evansi strains show some degree of kDNA loss, ranging from intact networks with complete maxicircles, but minicircle homogenization (see table), to complete kDNA loss [1,3]. Originally, the terms dyskinetoplastic and akinetoplastic described cells completely lacking a kDNA structure. However, the minicircle homogenization in even the mild forms of kDNA loss in some T. equiperdum strains is expected to result in complete loss of fully edited mRNAs, except cox2 and MURF2 [3]. Therefore, most recent publications, including this one, refer to all T. equiperdum and T. evansi strains as dyskinetoplastic while reserving the term akinetoplastic for strains completely lacking detectable kDNA [1,3,12]. Mitochondrial gene expression is essential in T. brucei [1], and the compensation for its loss in dyskinetoplastic forms was suggested to involve mutations in the nuclearly encoded γ subunit of the mitochondrial ATPase complex (see table) [3,13], a hypothesis that awaits experimental confirmation. In a stimulating article [2], Lun et al. suggested that dyskinetoplastic trypanosomes frequently and continuously evolve from T. b. brucei …