Kinetoplastid Biology and Disease

We discuss here some results which suggest that radically different maxicircle classes coexist within the same kinetoplast. These data, although tentative and incomplete, may provide a new outlook on the kinetoplast genome structure and expression. Report The kinetoplast genome is composed of a large heterogeneous population of minicircles and a small number of maxicircles. The maxicircles contain a conserved coding region of 16–17 kb and a non-coding "divergent" region which is highly variable in different strains and species [111]. It is believed that the population of maxicircles within a single mitochondrion is homogeneous. The first results contradicting this widely accepted assumption were obtained by Lee et al. in the early 90-es [12-16]. Drastic changes of kinetoplast DNA were observed in strains of Leishmania mexicana amazonensis selected in vitro for arsenite or tunicamycin resistance, and these changes were accompanied by amplification of extrachromosomal DNA in the nucleus [12]. It was demonstrated that a new maxicircle DNA variant appeared in all drug-resistant strains along with the extrachromosomal DNA amplification. This variant was characterized by an altered pattern of restriction sites [12,13], it had a radically different sequence of the cytochrome b gene [13] and also displayed extensive DNA sequence rearrangements in the divergent region [16]. Nevertheless, the mutant cells demonstrated a normal growth pattern and apparently retained functioning mitochondria [13]. Moreover, alterations of the minicircle kinetoplast DNA component ("minicircle dominance switch") were also observed: the predominant wild-type minicircle class was replaced by other minicircle classes in the drug-resistant cells [12-15]. It was hypothesized that the switch of minicircle dominance might alter editing pathways and help to generate functional proteins from the altered maxicircle sequence (for example, of the cytochrome b gene) [13]. Remarkably, very similar maxicircle variants appeared in different cloned cell lines independently selected for arsenite or tunicamycin resistance [13,16]. This fact lead the authors to suppose that there was more than one maxicircle type in the kinetoplast DNA network in all studied cell lines, and a minor maxicircle variant became prevalent after the selection for drug resistance [13]. Thus, the switch of maxicircle dominance might accompany the switch of minicircle dominance. This conclusion remains controversial because, rather unexpectedly, minor maxicircle classes were not detected directly by PCR or hybridization in the wild-type or drug-resistant strains and because the results of Lee et al. were never repeated by another group. However, no alternative mechanisms underlying the observed drastic changes of the kinetoplast DNA were proposed. Published: 18 September 2006 Kinetoplastid Biology and Disease 2006, 5:5 doi:10.1186/1475-9292-5-5 Received: 14 July 2006 Accepted: 18 September 2006 This article is available from: http://www.kinetoplastids.com/content/5/1/5 © 2006 Flegontov and Kolesnikov; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.