We report frequent losses of components of the classical nonhomologous end joining pathway (C-NHEJ), one of the main eukaryotic tools for end joining repair of DNA double-strand breaks, in several lineages of parasitic protists. Moreover, we have identified a single lineage among trypanosomatid flagellates that has lost Ku70 and Ku80, the core C-NHEJ components, and accumulated numerous insertions in many protein-coding genes. We propose a correlation between these two phenomena and discuss the possible impact of the C-NHEJ loss on genome evolution and transition to the parasitic lifestyle.IMPORTANCE Parasites tend to evolve small and compact genomes, generally endowed with a high mutation rate, compared with those of their free-living relatives. However, the mechanisms by which they achieve these features, independently in unrelated lineages, remain largely unknown. We argue that the loss of the classical nonhomologous end joining pathway components may be one of the crucial steps responsible for characteristic features of parasite genomes.

Institute of Parasitology Biology Centre Czech Academy of Sciences České Budějovice Czech Republic

Institute of Parasitology Biology Centre Czech Academy of Sciences České Budějovice Czech Republic Department of Parasitology Faculty of Science Charles University BIOCEV Prague Czech Republic

Institute of Parasitology Biology Centre Czech Academy of Sciences České Budějovice Czech Republic Faculty of Science University of South Bohemia České Budějovice Czech Republic

Martsinovsky Institute of Medical Parasitology Sechenov University Moscow Russia Life Science Research Centre and Institute of Environmental Technologies Faculty of Science University of Ostrava Ostrava Czech Republic

Wellcome Centre for Molecular Parasitology College of Medical Veterinary and Life Sciences University of Glasgow Glasgow Scotland

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