Telomeric retrotransposons show high propensity to form G-quadruplexes in various species

Abstract Background: Drosophila melanogaster telomeres are composed of three retrotransposons - Het-A, TART and TAHRE (HTT), which jump at the chromosome ends in orientation specific manner. Canonical telomeres, extended by telomerase, contain G-rich tandem repeats readily forming G-quadruplexes (G4). The G4 are formed just on one strand due to the GC strand bias. The HTT elements preserve the GC strand bias which is often found in telomere-targeting retrotransposons in other species as well. The G4-forming potential in these telomeric retrotranposons is unknown. Results: We searched for potential quadruplex-forming sequences (PQS) in the telomeric retrotransposons of the D. melanogaster fruit fly. We found that PQS are abundant in HTT elements and exhibit a strand-asymmetric distribution, being present only in non-coding strands and following the GC strand bias of canonical telomeres with possible G4 formation at G-rich ssDNA overhang. Our CD measurement showed that 13 out of 17 PQS formed G4 in vitro. This asymmetric PQS distribution in telomeric retrotransposons was common also for other Drosophila species, where evolutionary younger species have a tendency to accumulate more PQS. The majority (almost 70%) of PQS resides in the coding region of the gag gene and the regional PQS abundance correlates with the phenomenon of higher identity at the DNA level compared to amino acids. Moreover, the analysis of telomere-targeting retrotransposons from various species showed an independent selection of PQS-rich elements from distinct families. Conclusions: Our results support the importance of G4 in telomere maintenance and possibly represent a fundamental connection between telomerase-synthesized and non-canonical Drosophila telomeres.