Genomic immune system of ciliates: DNA elimination as a genome defense mechanism

Whole genome sequencing analyses are providing compelling evidence that pro- and eukaryote microbes, like multicellular organisms, have their life threatened by parasitic attacks. Bacteria and Archea face invading viral nucleic acids with an ‘inheritable DNA-encoded immunity’ (known as the CRISPR-Cas system) that recognizes foreign DNA from self DNA. In eukaryotic microbes that are exposed to invasions from both bacteria and viruses, bacteria are promptly made harmless either by digestion into food vacuoles, or by ‘domestication’ as symbionts. But the defence from viral attacks is much less effective. Foreign viral sequences can randomly insert into the cell genome, and may disrupt or deactivate vital genes. To fight this threat, ciliates rely on a unique model of inheritable genomic immune mechanism based on the evolution of two genomes, a germ-line one lying in the cell micronucleus and a somatic one lying in the macronucleus. The germ-line genome characterized by an orthodox chromosomic organization exposed to invasive viral DNA sequences is maintained transcriptionally silent. Only the somatic genome characterized by a unique sub-chromosomic organization is expressed. It is generated de-novo in coincidence with every sexual event from a copy of the micronuclear genome that is previously made free of any invasive DNA sequence by the activity of a small RNA-targeted DNA-deletion mechanism, called ‘Internal Eliminated Sequences (IES)-associated gene system’ by ciliatologists. The discovery, function and effects of this mechanism that eliminates invasive DNAs from the developing somatic genome will be the object of this contribution.