29.04.2019: The uncontrolled proliferation of transposable elements (TEs), short sequences of “parasitic” DNA, could lead to the extinction of numerous animal species. But evolution has found a way to stop this threat using so-called piRNAs, small RNAs of the host animal that reliably repress TE activity. A recently published study by Vetmeduni Vienna has now more closely examined this defence mechanism and shows for the first time that special accumulations of piRNAs, called piRNA clusters, can prevent the extinction of species through the unchecked proliferation of “selfish” DNA.

Transposable elements (TEs) are short stretches of DNA that multiply within genomes even when this activity has deleterious effects to the host. There also are several beneficial TE insertions, for example conferring resistance to insecticides. Overall, however, the benefit of TEs remains controversial and the current research suggests that TE insertions have no or little effect on host fitness. Due to the ability to proliferate within genomes, TEs frequently invade novel populations and species, whereby the unchecked proliferation of TEs may even lead to the extinction of host populations. It is thus essential for organisms to control the spread of TEs.

piRNA clusters stop deleterious TEs

In mammals and invertebrates, the proliferation of an invading transposable element (TE) is stopped when this parasitic DNA inserts itself into a piRNA cluster. This hypothesis is called the trap model. In a recently published study, Robert Kofler from the Institute of Population Genetics at Vetmeduni Vienna has now explored the dynamics of TE invasions under the trap model using large-scale computer simulations. Kofler came to the following conclusion: “We found that certain piRNA clusters offer a considerable benefit to host populations and effectively prevent their extinction from an uncontrollable proliferation of delirious TEs.”

TE invasion occurs in three phases

Kofler also showed that TE invasions have three distinct phases: First the TEs rapidly increase their numbers within the population; next there is an unstable suppression of TE proliferation through segregating insertions in piRNA clusters; and finally the TE is inactivated permanently by fixation of a cluster insertion, i.e. an insertion in all individuals in a population. The size of piRNA clusters was identified as a key factor affecting TE abundance. In an evaluation of the influence of different cluster architectures, the researcher found that a single non-recombining cluster – e.g. the somatic cluster called “flamenco” in the fruit fly Drosophila melanogaster – is more efficient in stopping invasions than clusters distributed over several chromosomes, such as germline clusters in Drosophila. “Applying this approach to real data of Drosophila, we found that the trap model reasonably well accounts for the abundance of germline TEs but fails to explain the abundance of somatic TEs. It remains completely unclear why this is the case. Further studies would therefore be desirable,” says Kofler.

Defence system with piRNAs offer high level of protection

The defence system against TEs relies on small RNAs, the so-called piRNAs. These form into clusters and can make up a substantial portion of the genome. In Drosophila melanogaster, for example, the fruit fly used in the trap model, piRNA clusters constitute about 3.5 % of the genome. Several studies have shown that a single TE insertion in a piRNA cluster can be sufficient to suppress the activity of a TE. These observations led to the trap model, according to which an invading TE proliferates within a host until at least one copy jumps into a piRNA cluster (the trap), triggering the production of piRNAs that stop the invading TE. piRNAs and piRNA clusters have been found in many different species, such as flies, worms, mice and humans. It is therefore likely that the trap model holds for most invertebrates and mammals. Despite this wide applicability, the dynamics of TE invasions under the trap model had previously not been much explored.

The article “Dynamics of transposable element invasions with piRNA clusters” by Robert Kofler was published in Molecular Biology and Evolution.