Evolutionary landscape of mosquito viral integrations

Abstract

The sequenced genome of the arboviral vector mosquito, Aedes albopictus, is replete with repetitive DNA and it harbors an unusually large number of endogenous viral sequences, collectively called Nonretroviral Integrated RNA Virus Sequences (NIRVS). NIRVS are enriched both within protein-coding gene exons and PIWI-interacting RNA (piRNA) clusters, where they encode piRNAs. Based on these features, NIRVS have been proposed to function as novel mosquito antiviral immune factors. However, the relative importance and contributions of different NIRVS as functional antiviral elements and their mechanisms of action remain open questions.We apply an analytical approach that intersects computational, evolutionary and molecular methods to identify NIRVS most likely affecting mosquito immunity. Using this strategy, we show that NIRVS are a highly dynamic component of the Ae. albopictus repeatome, which nevertheless maintains a core set of seemingly the oldest NIRVS with similarity to Rhabdoviruses. Population-level polymorphism of NIRVS varies depending on whether they occur in intergenic regions, piRNA clusters or are part of gene exons. NIRVS from piRNA clusters are differentially widespread in diverse populations but conserved at the sequence level. This is consistent with the hypothesis that they act analogously to fragments of transposable elements in piRNA clusters and contribute to piRNA-based immunity. Among NIRVS from gene exons, AlbRha52 and AlbRha12 have the hallmarks of domestication as they are fixed across populations, stably expressed, and as polymorphic at the sequence level as fast-evolving genes. Overall these results support the hypothesis that NIRVS contribute to mosquito immunity, potentially through diverse modes of action.

The Widespread Occurrence and Potential Biological Roles of Endogenous Viral Elements in Insect Genomes

“…A difference between F-NIRVS and NIRVS with similarity to rhabdoviruses (R-NIRVS) was seen in the first whole-genome survey of NIRVS across five geographical populations of Ae. albopictus: R-NIRVS were more widespread and included more ancient integrations based on accumulation of sequence changes than F-NIRVS (Pischedda et al, 2018), an interesting result considering that negative-strand RNA viruses like rhabdoviruses are thought to be evolutionarily more recent than positive-strand flaviviruses (Koonin et al, 2015).…”

“…albopictus, but rather are statistically significantly enriched in regions corresponding to PIWI-interacting RNA (piRNA)-generating loci, called piRNA clusters (Palatini et al, 2017;Whitfield et al, 2017). NIRVS are also differentially distributed in geographic populations (Pischedda et al, 2018). A difference between F-NIRVS and NIRVS with similarity to rhabdoviruses (R-NIRVS) was seen in the first whole-genome survey of NIRVS across five geographical populations of Ae.…”

Endogenous non-retroviral elements in genomes of Aedes mosquitoes and vector competence

“…Alternatively, NIRVS could also act as a keeper of persistent infection by maintaining a low level of viral replication, diminishing the negative impacts on the mosquito fitness. Nevertheless, analysis of natural mosquito populations revealed a high diversity of NIRVS at the intra- and inter-population levels (Houé et al unpublished data; [174]), suggesting many DNA recombination in NIRVS-surrounding areas. While many NIRVS have been found homologous to insect-specific flavi- and rhabdovirus [119], which are genetically related to pathogenic viruses, none was found homologous to Togaviridae family that contains only two insect-specific viruses described so far [175,176].…”