Subtelomere

Subtelomeres are considered to be the most distal (farthest from the centromere) region of unique DNA on a chromosome, and they are unusually dynamic and variable mosaics of multichromosomal blocks of sequence.

The two domains differ in sequence content and extent of homology to other chromosome ends, and they are often separated by a stretch of degenerate telomere repeats (TTAGGG) and an element called 'core X', which is found at all chromosome ends and contains an autonomously replicating sequence (ARS) and an ABF1 binding site.

[2][3] The proximal domain is composed of variable interchromosomal duplications (<1-30 kb); this region can contain genes such Pho, Mel, and Mal.

For example, in Plasmodium falciparum during interphase of the erythrocytic stage, the chromosomic extremities are gathered at the cell nucleus periphery, where they undergo frequent deletion and telomere position effect (TPE).

In other species, several parasites such as Plasmodium and Trypanosoma brucei have developed sophisticated evasion mechanisms to adapt to the hostile environment posed by the host, such as exposing variable surface antigens to escape the immune system.

[9][10] For example, the genes belonging to the var family in Plasmodium falciparum (agent of malaria) are mostly localized in subtelomeric regions.

Other factors such as non-coding RNA produced in subtelomeric regions adjacent or within var genes may contribute as well to antigenic variation.

[11][12] In Trypanosoma brucei (agent of sleeping sickness), variable surface glycoprotein (VSG) antigenic variation is a relevant mechanism used by the parasite to evade the host immune system.

To contrast with Plasmodium falciparum, in Trypanosoma brucei, antigenic variation is orchestrated by epigenetic and genetic factors.

[13][14] In Pneumocystis jirovecii major surface glycoprotein (MSG) gene family cause antigenic variation.

A second subtelomeric gene family, MSR, is not strictly regulated at the transcriptional level, but may contribute to phenotypic diversity.

This deletion is thought to cause disease owing to a position effect that influences the transcription of nearby genes, rather than through the loss of the repeat array itself.

[1] The advantages of subtelomeres have been studied in different species such as Plasmodium falciparum,[1] Drosophila melanogaster,[1] and Saccharomyces cerevisiae,[1] since they have similar genetic elements to humans, not accounting for length and sequence.

The knockout of subtelomeres in Schizosaccharomyces pombe cells does not affect the regulation of multiple stress responses, when treated with high doses of hydroxyurea, camptothecin, ultraviolet radiation, and thiabendazole.

Sgo2 interacts with subtelomeres during interphase; middle of the G2 phase and plays a major role in forming "knob", which is a highly condensed chromatin body.