Identification of the Telomere elongation Mutation in Drosophila

Telomeres in Drosophila melanogaster, which have inspired a large part of Sergio Pimpinelli work, are similar to those of other eukaryotes in terms of their function. Yet, their length maintenance relies on the transposition of the specialized retrotransposons Het-A, TART, and TAHRE, rather than on the activity of the enzyme telomerase as it occurs in most other eukaryotic organisms. The length of the telomeres in Drosophila thus depends on the number of copies of these transposable elements. Our previous work has led to the isolation of a dominant mutation, Tel(1), that caused a several-fold elongation of telomeres. In this study, we molecularly identified the Tel(1) mutation by a combination of transposon-induced, site-specific recombination and next-generation sequencing. Recombination located Tel(1) to a 15 kb region in 92A. Comparison of the DNA sequence in this region with the Drosophila Genetic Reference Panel of wild-type genomic sequences delimited Tel(1) to a 3 bp deletion inside intron 8 of Ino80. Furthermore, CRISPR/Cas9-induced deletions surrounding the same region exhibited the Tel(1) telomere phenotype, confirming a strict requirement of this intron 8 gene sequence for a proper regulation of Drosophila telomere length.

Automated summary

The length of telomeres in Drosophila melanogaster is maintained through the transposition of retrotransposons Het-A, TART, and TAHRE, unlike most other eukaryotes that rely on telomerase activity. A dominant mutation Tel(1) causing elongation of telomeres was identified in this study and molecularly characterized to be a 3 bp deletion within intron 8 of the Ino80 gene. Deletions induced by CRISPR/Cas9 in the same region exhibited the Tel(1) telomere phenotype, confirming the importance of this intron 8 gene sequence in regulating Drosophila telomere length.