Fig. 7: DNA replication programming in T. brucei dictates compartmentalised genome stability.

A summary of DNA replication functions that denote stability and instability across the T. brucei genome. The transcribed cores of the megabase chromosomes are replicated from multiple origins, the earliest acting of which coincide with centromeres. Many of the centromeres contain 177 bp repeats that are found in all sub-megabase chromosomes, where the repeats act as DNA replication origins. The subtelomeres of the megabase chromosomes are largely devoid of origins and are unstable relative to the cores. VSG bloodstream expression sites (BESs) are found adjacent to the telomeres of megabase and sub-megabase chromosomes. Only the single actively transcribed VSG BES displays early S-phase DNA replication, which is derived from the telomere and likely results in head-on collisions with monoallelic BES transcription. Early replication of the single VSG BES transcribed in mammal-infective parasites does not occur in parasites within the tsetse fly vector, where transcription of all VSG BESs is silenced. Elements of the figure (the fly and the human) were created in BioRender. McCulloch, R. (2025) https://BioRender.com/w43b159.