A theoretical study of random segregation of minicircles in trypanosomatids

The kinetoplast (k) DNA network of trypanosomatids is made up of approximat ely 50 maxicircles and the order of 10(4) minicircles. It has been proposed , based on various observations and experiments, that the minicircles are r andomly segregated between daughter cells when the parent cell divides. In this paper, this random segregation hypothesis is theoretically tested in a population dynamics model to see if it can account for the observed phenom ena. The hypothesis is shown to successfully explain! in Leishmania tarento lae, the observation that there are a few major and many minor minicircle c lasses, the fluctuations of minicircle class copy numbers over time, the lo ss of non-essential minicircle classes? the long survival times of a few of these classes and that these classes are likely to be the major classes wi thin the population. Implications of the model are examined for trypanosoma tids in general, leading to several predictions. The model predicts variati on in network size within a population, variation in the average network si ze and large-scale changes in class copy number over long time-scales, an e volutionary pressure towards larger network sizes, the selective advantage of non-random over random segregation, very strong selection for the amplif ied crass in Crithidia fasciculata if its minicircles undergo random segreg ation and that Trypanosoma brucei may use sexual reproduction to maintain i ts viability.