The diversity, structure and function of heritable adaptive immunity sequences in the Aedes aegypti genome

Abstract

18The Aedes aegypti mosquito is a major vector for arboviruses including 19 dengue, chikungunya and Zika virus. Combating the spread of these viruses 20 requires a more complete understanding of the mosquito immune system. 21 Recent studies have implicated genomic endogenous viral elements (EVEs) 22 derived from non-retroviral RNA viruses in insect immunity. Because these 23 elements are inserted into repetitive regions of the mosquito genome, their large-24 scale structure and organization with respect to other genomic elements has 25 been difficult to resolve with short-read sequencing. To better define the origin, 26 diversity and biological role of EVEs, we employed single-molecule, real-time 27 sequencing technology to generate a high quality, long-read assembly of the Ae. 28 aegypti-derived Aag2 cell line genome. We leverage the quality and contiguity of 29 this assembly to characterize the diversity and genomic context of EVEs in the 30 genome of this important model system. We find that EVEs in the Aag2 genome 31 are acquired through recombination by LTR retrotransposons, and organize into 32 larger loci (>50kbp) characterized by high LTR density. These EVE containing 33 loci are associated with increased transcription factor binding sight density and 34 increased production of anti-genomic piRNAs. We also detected piRNA 35 processing corresponding to on-going viral infection. This global view of EVEs 36 and piRNA responses demonstrates the ubiquity and diversity of these heritable 37

Insect genomes: progress and challenges

“…Chromosome‐level assembly can be obtained by using HiC scaffolding and BioNano. These two techniques were used together or solely on insect genomes recently, such as T. castaneum (red flour beetle; Shelton et al ., ), A. mellifera (western honey bee), Galleria mellonella (greater wax moth), A. aegypti (yellow fever mosquito; Matthews et al ., ; Whitfield et al ., ), Trichoplusia ni (cabbage looper; Fu et al ., ) and Cydia pomonella (codling moth). We can expect the coming of an era of high‐quality insect genomes. In‐depth analysis of insect genome data is a bottleneck at present.…”

“…In 2017, the A. aegypti genome was greatly improved to yield a chromosome-level genome assembly using the Hi-C technique (Dudchenko et al, 2017). Long-read assembly was also used to resolve large repetitive regions for a cell line (Whitfield et al, 2017), which were unable to be determined by previous methods. Recently, a better assembly of mosquito genomes was implemented by combining both the PacBio and Hi-C techniques (Matthews et al, 2018).…”

The dual lifestyle of genome‐integrating virophages in protists

“…Mavirus joins an illustrious list of endogenous virus elements (EVEs) found in eukaryotic genomes. In principle, viruses of any Baltimore class can eventually become part of a host genome, although at highly different frequencies …”

“…In principle, viruses of any Baltimore class can eventually become part of a host genome, although at highly different frequencies. [44][45][46][47][48] Retroviral elements are the most abundant class of endogenous viruses in vertebrates because of the mandatory genome integration step of their replication cycles. 49,50 The retroviral RNA is delivered to the cytoplasm, reverse-transcribed, and the dsDNA genome migrates into the nucleus via nuclear pores or during cell division.…”

“…Eukaryotic genomes also contain endogenous sequences derived from non-reverse transcribing RNA and DNA viruses, even though most of these viruses do not encode integrases. 46,60,61 Instead, integration could be mediated in trans by hostencoded reverse transcriptases and integrases, [62][63][64][65][66] by recombination with LTR retrotransposons, 45 or as a byproduct of DNA repair when viral DNA is used to patch double-stranded breaks in the host chromosome via nonhomologous end joining. 67 In contrast to most nonretroviral EVEs, which represent truncated versions of virus genomes, adeno-associated virus (AAV) integrates as a fulllength element into human and primate genomes.…”