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Drosophila Telomeres

Drosophila, commonly known as fruit flies have telomeres which are structured differently than most eukaryotes. Like all eukaryotes, they contain linear chromosomes with telomeres at the end. The problem all eukaryotes face is since their chromosomes are linear they shorten at the telomere after each cell division. Most eukaryotes use telomerase, an enzyme which can lengthen the telomeres to prevent this problem. Drosophila do not have telomerase so instead they have three non-long terminal repeats (non-LTRs) retrotransposons located at the end of the telomere. These three elements can transpose to the chromosome ends to maintain the length of the ends of the chromosomes which shorten after each replication. Proteins are associated with the telomeres to ensure stability. Two known proteins are Heteterochromatin Protein 1 (HP1)and HP1/ORC associated Protein (HOAP). The evolution of the mechanism Drosophila uses to maintain it's telomeres has been hypothesized to result from first a loss of telomerase and then an alternative method of telomere maintenance arose. The supported hypothesis is the transposons were already present in the telomere and they were upregulated to cause an increase in expression in order to be able to function as the telomere lengthening mechanism.

Structure

Starting from the very end of the telomere there is first the chromosome cap. In Drosophila this is made up of HP1 and HOAP. Specific binding of HP1 to HOAP forms a telomere capping complex. The telomere capping complex binds to the end of the telomere regardless of sequence. Moving toward the center of the chromosome, the next part of the Drosophila telomere is the three non-LTR retrotransposons. The three retrotransposons (TART, Het-A, and TAHRE) all have large 3’ untranslated regions (3’-UTRs)  which contain promoter regions and all of the 3’-UTRs have the tendency to form G-quadruplex structures. G-quadruplex structures are structures formed by regions of DNA rich in guanine. As with all non-LTR retrotransposons that can mobilize, TART, HeT-A, and TAHRE have oligonucleotide adenine tails which are short DNA regions of just adenine that are orientated toward the centromere. Finally the last segment of the Drosophila telomere is the telomere associated segment (TAS). TAS are complex repeats found in almost all eukaryotic telomeres.

Mechanism

The telomeres elongate by first transcribing TART, HeT-A, and TAHRE. The mRNA transcripts are exported out of the cell's nucleus and into the cytoplasm where the mRNA is used to translate a GAG-like Protein. The GAG-like protein can bind to mRNA can import it back into the cell’s nucleus. Through an unknown interaction the mRNA is position at the 3’ hydroxyl at the end of the chromosome and uses this as a primer. Reverse transcriptase, an enzyme which transcribes RNA molecules into DNA molecules incorporates the mRNA sequence into the telomere as DNA, lengthening it. DNA repair mechanisms using the newly synthesized DNA strand as a template complete the other side finishing the telomere elongation.

Evolution

Although it isn’t well know why Drosophila uses non-LTR retrotransposons as the mechanism, it is thought that as Drosophila evolved it lost the typical eukaryotic telomere machinery (sequence dependence of capping and telomerase). Due to the lack of conventional telomere lengthening the transposable elements which were already present and could provide a viable alternative to prevent the telomeres from shortening after each cell division were regulated to increase in expression and over evolutionary time became the new mechanism Drosophila rely on to maintain their telomeres.