Involvement of non-LTR retrotransposons in mammal cancer incidence and ageing

Abstract

AbstractThe presence in nature of closely related species showing drastic differences in lifespan and cancer incidence has recently increased the interest of the scientific community on these topics. In particular, the adaptations and genomic characteristics underlying the evolution of cancer-resistant and long-lived species have recently focused on the presence of alterations in the number of non-coding RNAs, on epigenetic regulation and, finally, on the activity of transposable elements (TEs). In this study, we compared the content and dynamics of TE activity in the genomes of four rodent and six bat species exhibiting different lifespans and cancer susceptibility. Mouse, rat and guinea pig (short-lived and cancer-prone organisms) were compared with the naked mole rat (Heterocephalus glaber) which is the rodent with the longest lifespan. The long-lived and cancer-resistant bats of the genera Myotis, Rhinolophus, Pteropus and Rousettus were instead compared with the Molossus, which is instead a short-lived and cancer-resistant organism. Analyzing the patterns of recent accumulations of TEs in the genome in these species, we found a strong suppression or negative selection to accumulation, of non-LTR retrotransposons in long-lived and cancer-resistant organisms. On the other hand, all short-lived and cancer-prone species have shown recent accumulation of this class of TEs. Among bats, the Molossus molossus turned out to be a very particular species and, at the same time, an important model because, despite being susceptible to rapid ageing, it is resistant to cancer. In particular, we found that its genome has the highest density of SINE (non-LTR retrotransposons), but, on the other hand, a total lack of active LINE retrotransposons. Our hypothesis is that the lack of LINEs presumably makes the Molossus cancer resistant due to lack of retrotransposition but, at the same time, the high presence of SINE, may be related to their short life span due to “sterile inflammation” and high mutation load. We suggest that research on ageing and cancer evolution should put particular attention to the involvement of non-LTR retrotransposons in these phenomena.