Assembly of the Genome of the Disease Vector Aedes aegypti onto a Genetic Linkage Map Allows Mapping of Genes Affecting Disease Transmission

Abstract

The mosquito Aedes aegypti transmits some of the most important human arboviruses, including dengue, yellow fever and chikungunya viruses. It has a large genome containing many repetitive sequences, which has resulted in the genome being poorly assembled — there are 4,758 scaffolds, few of which have been assigned to a chromosome. To allow the mapping of genes affecting disease transmission, we have improved the genome assembly by scoring a large number of SNPs in recombinant progeny from a cross between two strains of Ae. aegypti, and used these to generate a genetic map. This revealed a high rate of misassemblies in the current genome, where, for example, sequences from different chromosomes were found on the same scaffold. Once these were corrected, we were able to assign 60% of the genome sequence to chromosomes and approximately order the scaffolds along the chromosome. We found that there are very large regions of suppressed recombination around the centromeres, which can extend to as much as 47% of the chromosome. To illustrate the utility of this new genome assembly, we mapped a gene that makes Ae. aegypti resistant to the human parasite Brugia malayi, and generated a list of candidate genes that could be affecting the trait.

The genetic architecture of a complex trait: Resistance to multiple toxins produced by Bacillus thuringiensis israelensis in the dengue and yellow fever vector, the mosquito Aedes aegypti

“…These two laboratory strains have strikingly different origins and histories: the LVP strain was originally collected from West Africa and has been maintained in culture since 1936 in Liverpool (UK), while the Bora-Bora strain was collected in French Polynesia and maintained in Grenoble (France) since 1998, and therefore their genetic make-up is likely to be very different. We have detected a much higher rate of misassemblies (70% of the supercontigs with multiple markers) in our QTL study as compared to the linkage map based on a cross involving the LVP strain (14%; Juneja et al, 2014). Our results not only confirm that physical mapping and contig assembly in the LVP reference genome are subject to caution (Nene et al, 2007;Timoshevskiy et al, 2013), but they also suggest that genome organization might differ between populations of Ae.…”

“…When investigating misassemblies at a more local scale (within supercontigs), we detected that among the 61 pairs of loci situated on the same supercontig according to physical mapping, 18 (29.5%) only were located less than 10cM apart on our map. Overall, among the 121 supercontigs positioned both on our map and on Juneja et al (2014)"s, 23 (19.0%) had already been reported as misassembled (Juneja et al, 2014). This large discrepancy between linkage maps and supercontig sequences suggests a high level of genome plasticity in Aedes aegypti previously highlighted by other works (Bernhardt et al, 2009;Macdonald and Sheppard, 1965).…”

“…This genetic map harbors 229 SNP markers mapped across the three linkage groups for a total length of 311.9 cM (Figure 2). It is slightly longer than the most complete genetic map published so far for this species (235 cM; Juneja et al, 2014), which consists of more than 2,000 RAD tag markers. In agreement with other authors (Juneja et al, 2014;Timoshevskiy et al, 2013), our study revealed some discrepancies between Ae.…”

The Physical Genome Mapping ofAnopheles albimanusCorrected Scaffold Misassemblies and Identified Interarm Rearrangements in GenusAnopheles

“…However, the position of microsatellite 0008 in the linkage map contradicted the location of the homologous sequence on the physical map (Figure 6). Some discrepancies between physical and genetic maps can be seen in other comparisons, and they are often associated with local variation in genetic recombination (Timoshevskiy et al 2013; Juneja et al 2014; Shearer et al 2014). For An.…”

Vector competence of Aedes aegypti mosquitoes for filarial nematodes is affected by age and nutrient limitation

“…malayi was originally segregating in the Liverpool strain, but in order to sequence the mosquito genome several rounds of inbreeding were required (Nene et al, 2007) and resistance became fixed (Juneja et al, 2014 …”