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.

Department of Parasitology Faculty of Science Charles University BIOCEV Prague Czech Republic

Faculty of Science University of South Bohemia České Budějovice Czech Republic

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

Life Science Research Centre and Institute of Environmental Technologies Faculty of Science University of Ostrava Ostrava Czech Republic

Martsinovsky Institute of Medical Parasitology Sechenov University Moscow Russia

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

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Leishmania mexicana telomeres at high resolution: Ku80, TERT, and alternative lengthening mechanisms

Comparative genomic analysis of trypanosomatid protists illuminates an extensive change in the nuclear genetic code

Evolutionary Insights into the Length Variation of DNA Damage Response Proteins Across Eukaryotes

Identification of diverse RNA viruses in Obscuromonas flagellates (Euglenozoa: Trypanosomatidae: Blastocrithidiinae)

Blastocrithidia nonstop mitochondrial genome and its expression are remarkably insulated from nuclear codon reassignment

Efficient CRISPR/Cas9-mediated gene disruption in the tetraploid protist Giardia intestinalis

Ku80 is involved in telomere maintenance but dispensable for genomic stability in Leishmania mexicana

Genomic analysis finds no evidence of canonical eukaryotic DNA processing complexes in a free-living protist

Diverse telomeres in trypanosomatids